1 Thursday, 1 December 2011
2 (10.00 am)
3 MR MACAULAY: Good morning, my Lord. The next witness
4 I would like to call is Dr Warren.
5 DR RODERIC ELLIS WARREN (sworn)
6 Examination by MR MACAULAY
7 MR MACAULAY: Dr Warren, are you Roderic Ellis Warren?
8 A. I am.
9 Q. Could you tell the Inquiry what position you hold at
11 A. I am consultant medical microbiologist to the Shrewsbury
12 and Telford Hospital NHS Trust and honorary consultant
13 microbiologist to the Robert Jones and Agnes Hunt
14 Orthopaedic Hospital.
15 Q. Is that a full-time post you hold at present?
16 A. No, I have drawn my pension and I now work alternate
18 Q. Perhaps you can give the Inquiry some idea as to what
19 your duties are at present?
20 A. My duties at present involve, basically, assessing the
21 epidemiology of hospital-acquired infection across the
22 whole Shropshire health economy and the little bit of
23 Wales that we also cover, and producing a regular
24 monthly report on acquisition of infection.
25 Previously, I was very closely involved and led the
1 microbiology team in Shropshire, from 1993 onwards, in
2 doing a normal consultant microbiologist job, and, in
3 addition, I had responsibility as the group director of
4 the then Public Health Laboratory Service for
5 laboratories in Heartlands Hospital in Coventry and in
6 Stoke-on-Trent as well.
7 Q. Perhaps you can tell us, when did you have the benefit
8 of drawing your pension?
9 A. Two years ago.
10 Q. So up until then, you had the duties that you just
11 mentioned --
12 A. Exactly so.
13 Q. -- on a full-time basis?
14 A. Exactly so.
15 Q. Were you attached to a particular hospital at that time?
16 A. The laboratory was based largely in the Royal Shrewsbury
17 Hospital as a bacteriology laboratory. In addition,
18 I had organised, when I arrived there, in 1993, that all
19 the virological services were provided out of
20 Telford Hospital, which is about 20 miles away.
21 Q. Would you then, in that previous post, have laboratory
22 duties and also ward duties?
23 A. Yes. Ward duties, difficult, bearing in mind that,
24 largely, I provided services on the same site, in other
25 words, in the Shrewsbury area, and the
1 Oswestry Hospital, which was 20 miles in the opposite
2 direction. In fact, I had four colleagues and we
3 divided up the patch such that two microbiologists were
4 largely responsible for Telford Hospital and two were
5 largely responsible for Shrewsbury and Oswestry
6 Hospitals, and I was in the latter category.
7 Q. The Royal Shrewsbury Hospital you mentioned, what sort
8 of size of hospital is that?
9 A. That is a 500-bedded hospital; Telford Hospital is about
10 300 beds; Oswestry is about 220 beds and has a regional
11 spinal injuries unit and is one of the five specialist
12 orthopaedic hospitals in England. It has a very large
13 prosthetic joint replacement programme.
14 We also had responsibility for six community
15 hospitals, which were basically one ward each scattered
16 across the face of Shropshire and Wales.
17 Q. Dr Ward, if I could ask you to slow down a little bit so
18 the transcribers can note your every word?
19 A. Sure.
20 Q. Can we then look at your CV, and I will have this put on
21 the screen for you, but you may have a copy in front of
22 you. It is INQ02830001. On the front page of the CV
23 you set out an executive summary, and if we turn to
24 page 2, looking under the heading for your
25 qualifications, can we see that you have an MA and your
1 medical degree from the University of Cambridge; is that
3 A. That's correct.
4 Q. We can also see that you are a Fellow of the Royal
5 College of Pathologists since September 1998?
6 A. That's right.
7 Q. You then set out your clinical posts, and you give us
8 some detail over the next number of pages, up to page 5,
9 of posts you held prior to your post as lead consultant
10 microbiologist at the Royal Shrewsbury Hospital; is that
12 A. That's right.
13 Q. If we look at page 5 of your CV, do you set out there
14 your duties and your achievements in that particular
15 position from January 2003 onwards?
16 A. Yes, I do.
17 Q. If we turn to page 6, you give us some insight into
18 other appointments you had, and you also provide us with
19 some information about your medical advisory experience
20 in the NHS; is that right?
21 A. That's right.
22 Q. The reference to 2005 and to the current C. difficile
23 advisory subgroup, first of all, is that something you
24 are still involved with?
25 A. No, that subgroup on Clostridium difficile stood down
1 with the provision of a report that was widely published
2 in the NHS.
3 Q. When was that?
4 A. That was 2005. The report was actually produced --
5 actually published in 2008.
6 Q. Was that into a particular healthcare area, or --
7 A. That was in the area of Clostridium difficile.
8 Q. Was that something you prepared, then, for the Health
9 Protection Agency?
10 A. Yes, with the Department of Health representation.
11 Q. Clearly, you have had extensive involvement in a number
12 of different committees over the years, and you give us
13 some insight into that over the next couple of pages.
14 If we turn to page 8 of the report, do you provide there
15 information in relation to your involvement with
16 a number of professional associations and societies?
17 A. Yes, I do. The major areas I have been involved in are
18 the Drug and Therapeutics Bulletin, which was produced
19 where I was on the editorial board, and that was
20 produced and distributed to all hospitals in England,
21 and I was the article editor for antibiotics for some
22 10 to 15 years.
23 I have also served twice on the council and once as
24 treasurer for the British Society of Antimicrobial
1 Q. Turning to page 9, then, of your CV, you indicate
2 towards the bottom that you have also had teaching and
3 examining experience; is that correct?
4 A. That's true, some time ago.
5 Q. Then, I think, from page 10 onwards -- and that is from
6 page 10 through to certainly page 24 or 25 -- you
7 provide us with details of publications that you have
8 had some involvement with; is that right?
9 A. That's correct.
10 Q. You seem to have had fairly extensive -- you have been
11 fairly productive, I think, over the years. Can you
12 give me a general understanding as to what areas you
13 have sought to cover?
14 A. Well, most of my research areas have arisen out of my
15 work as a consultant medical microbiologist or with the
16 Drug and Therapeutics Bulletin, where -- the publication
17 involves multiple people.
18 I have been particularly interested down the years
19 in immunocompromised patients and, latterly, after my
20 move to Shrewsbury, in orthopaedic patients.
21 I have been interested in the whole area of
22 antibiotics, antibiotic-resistant, and what goes on in
23 the gut flora which gives rise to infection.
24 Q. I think you have also -- in this list I think we have on
25 page 23 some information in connection with chapters in
1 books that you have contributed to; is that right?
2 A. That is correct, some time ago, again.
3 Q. The section "In preparation", which comes before the
4 section dealing with book chapters, certainly you seem
5 to have had some investigation into C. difficile.
6 I think we see that in the second entry. Particularly
7 in relation to ribotyping and ribotype 027?
8 A. That's true.
9 Q. Is that ongoing?
10 A. Yes, that is an ongoing thing. I have produced one or
11 two posters, but no publication in that area, but I have
12 ongoing research in that area and take a particular
13 interest in it.
14 Q. If we can lay aside your CV, then, and turn to your
15 involvement in this particular case, I think it is the
16 case that you have been asked to look at the records of
17 a number of patients who had been at the Vale of Leven
18 over the period that we are concerned with; is that
20 A. Yes, 19 patients in all.
21 Q. I think you have prepared reports in respect of each of
22 these patients?
23 A. I have, and also an overview report.
24 Q. Just to confirm, you have never worked in the
25 Vale of Leven Hospital?
1 A. No.
2 Q. Have you ever been to the hospital?
3 A. Not as far as I can recall.
4 Q. In preparation for looking at the cases, and to give you
5 some understanding as to what the hospital might be
6 like, were you provided with the junior doctors'
8 A. I was, indeed. Yes.
9 Q. We can perhaps put that on the screen, it is at
10 GGC21720001. I think this is the first page of
11 the document that you were provided with. According to
12 the information provided here, it was a hospital of
13 approximately 180 beds with the services set out there;
14 is that correct?
15 A. That is correct. That is a relatively small hospital.
16 Q. Certainly in comparison to your own hospital?
17 A. Indeed, sir.
18 Q. Additionally, were you provided with a number of
19 documents that may have been in use at the
20 Vale of Leven Hospital to provide guidelines to the
21 doctors as to how to prescribe medications?
22 A. Yes, that's so. I think many of them were unheaded and
23 undated, and it is difficult to be certain what was in
24 use in the relevant period from the beginning of 2007 to
1 Q. If I can then just look at some of that, could you have
2 in front of you GGC18270001? We have on the screen what
3 bears to be the Greater Glasgow and Clyde formulary
4 first edition, August 2007; is that right?
5 A. Yes, indeed.
6 Q. I think you did look at this?
7 A. Yes. I considered that, as the hospital was part of
8 the Greater Glasgow and Clyde Health Board at the time,
9 this was a material guide to antibiotics during the
10 relevant period, the second edition being provided
11 in August 2008, which is after the relevant period where
12 I had been looking at what went on.
13 Q. We will be looking at that, not really with you, but
14 with other witnesses.
15 If I can take you to page 37 of this document, we
16 have here a section dealing with infections, and the
17 introduction tells us that antibiotics not listed in the
18 text may occasionally be prescribed on the advice of
19 a microbiologist or infectious disease physician.
20 Can I just ask you about that? Is it fair to say
21 that, although information is given in the formulary,
22 these are guidelines to the clinician, and the clinician
23 may, on occasion, depending on the circumstances, move
24 away from the guidelines?
25 A. I think, if it is appropriate, whatever "appropriate"
1 means, and "appropriate" means having due regard to the
2 context of the expert advice -- because this formulary,
3 like most formularies, is set out by drug and, of
4 course, the clinician is dealing with clinical
5 conditions, which is, if you like, the other way around:
6 clinical condition leading to suspected organism leading
7 to appropriate chemotherapy.
8 Q. What would you take from that introduction in relation
9 to the situation if a clinician did decide to move away
10 from the current guidelines? Would you expect the
11 clinician to confer with the microbiologist before doing
12 so, or would you expect the clinician, really, off his
13 own bat to do that?
14 A. Well, I think it depends on whether it is a specialist
15 situation or not. I mean, I think, for example, in my
16 experience with leukemia doctors, they might well use,
17 for example, drugs outside this guideline, but I would
18 expect a general physician to do what you said; in other
19 words, to stick with this guideline and to ask advice if
20 he was uncertain or wished to prescribe an agent outside
21 this basic list.
22 There was, at the end of this document, a list of
23 additional agents that might be prescribed after
24 consultation with a microbiologist or an infectious
25 diseases physician.
1 Q. Certainly that is what is envisaged in the introductory
2 section here?
3 A. That's right.
4 Q. If we look then towards the bottom section of the page,
5 can we see at 184.108.40.206 a heading "Broad-spectrum
6 penicillins", and there is reference to amoxicillin. Is
7 guidance given here as to when amoxicillin might
8 appropriately be prescribed?
9 A. Yes, I would say that was true. Of course, whether or
10 not an agent is appropriate may be influenced by
11 a laboratory report as to whether the suspected
12 infecting organism is likely to be resistant to that
13 agent. So, for example, urinary tract infections are
14 commonly caused by an organism called E. Coli that is
15 very commonly now resistant to amoxicillin. It wasn't
16 when it was introduced, but it is now.
17 Q. So then you would have to go down another route?
18 A. Exactly so.
19 Q. Co-amoxiclav is the next antibiotic that is mentioned
20 there. Just looking to this formulary, are you able to
21 assist the Inquiry, just focusing on what is said here,
22 for what it is being envisaged the co-amoxiclav would be
24 A. Well, it is envisaged here that it would be used for
25 amoxicillin-resistant strains, when amoxicillin would
1 otherwise be indicated, I think. It is quite a limited
3 We should remember that co-amoxiclav is actually two
4 compounds mixed together in the same preparation. The
5 basic antibiotic is amoxicillin, and it contains
6 clavulanic acid, which blocks the action of many, but
7 not all, beta-lactamases which confer amoxicillin
9 Q. When I read that:
10 "Therefore, co-amoxiclav should be reserved for
11 infections suspected of being due to
12 amoxicillin-resistant beta-lactamase-producing strains."
13 The reference to beta-lactamase, can you --
14 A. Okay. A beta-lactamase is an enzyme produced by
15 bacteria that destroys some penicillins, or
16 cephalosporins, and confers resistance to amoxicillin.
17 Q. If we turn to page 38, at 5.1.2, there is a heading
18 "Cephalosporins and other beta-lactams", and the first
19 reference is to "cephalexin". We can read:
20 "Generally used for urinary tract infections where
21 trimethoprim is not appropriate."
22 So there is some guidance given there to the
24 A. That is right. That is right. It is appropriate in
25 upper urinary tract infections. There are other
1 alternatives for lower urinary tract infections. One
2 commonly used these days as an alternative is a urinary
3 antiseptic called nitrofurantoin.
4 Q. I think we see some reference to that in other
6 A. We do.
7 Q. If we turn to page 37, at 5.1.8 there is reference to
8 trimethoprim, and the suggestion here is that that is
9 used primarily for urinary tract infections; is that
11 A. That's right. Trimethoprim resistance has also become
12 very common, however, and is often linked to amoxicillin
13 resistance. About 80 per cent of amoxicillin-resistant
14 strains, in my experience, will be resistant to
15 trimethoprim too. So in advocating trimethoprim for
16 urinary tract infection, you have the proviso that the
17 strain is sensitive, and many are not.
18 Q. But if we turn to page 40, under the general heading of
19 "Urinary tract infections", can we see that trimethoprim
20 seems to be considered as the first choice for
21 uncomplicated UTIs?
22 A. I think that is true. You have to understand what is
23 meant by "uncomplicated", and that normally implies
24 lower urinary tract infection or cystitis without
1 Q. Finally, on looking at this document while we are on
2 that -- go back, in fact, to page 39 of the Lextranet
3 numbers, we have reference at 5.1.11 to metronidazole,
4 which we have heard quite a bit about in this Inquiry.
5 I don't think here it is being discussed in the context
6 of C. difficile; is that right?
7 A. Well, C. difficile is an anaerobic infection, for what
8 it is worth. So you could say it is included in the
9 first sentence.
10 Q. Vancomycin, we have heard some evidence on that and its
11 relevance to C. difficile. Did you see any reference to
12 vancomycin in this particular formulary?
13 A. I can't actually recall, but I'm sure it will be there.
14 Vancomycin is a drug that is normally given
15 intravenously to treat systemic infections. It was
16 widely regarded as the drug of choice, and, indeed, the
17 drug of last resort for serious Gram-positive
18 infections. A Gram stain is a way of classifying
19 bacteria and it was used largely for MRSA infections.
20 The drug is not absorbed normally, except perhaps in
21 a little extent to renal failure, not absorbed from
22 the -- by mouth, but the drug has been used,
23 particularly orally, to treat the Gram-positive
24 infection Clostridium difficile in the gut, and was, in
25 fact, the first agent that was used in treating
1 Clostridium difficile infection when it was recognised
2 in the late 1970s.
3 Q. Can we then leave that document aside and move on to
4 another document --
5 MR KINROY: My Lord, before we leave that, I wonder if my
6 learned friend would permit a quick look at the part of
7 the document which, at the end, lists the additional
8 agents that might be prescribed after consultation with
9 a microbiologist or infectious disease physician, if we
10 might look at the criteria for that?
11 MR MACAULAY: Can you tell me what page?
12 MR KINROY: My Lord, I am very much handicapped. I can't do
13 that. It may be necessary to come back to this.
14 LORD MACLEAN: It is a page in the formulary that Dr Warren
15 is referring to.
16 MR KINROY: It might be more realistic to come back to this,
17 my Lord, but I have a recollection of there being
18 certain criteria for this. I don't want to interrupt
20 LORD MACLEAN: As you please, Mr MacAulay.
21 MR MACAULAY: I am happy to do that. Page 7 of
22 the Lextranet numbering, if we can put that back on the
23 screen. This may be the provision.
24 We are looking at the heading "Non-formulary
1 MR KINROY: My interest, my Lord, was the specific drugs
2 which required consultation with the microbiologist or
3 infectious diseases specialist.
4 MR MACAULAY: That is page 37, then, is it?
5 LORD MACLEAN: We have been there.
6 MR KINROY: My Lord, I will have to try to come back to
7 this, with my learned friend's cooperation, after the
8 break. I think that will be much more effective.
9 MR MACAULAY: I had taken you, Dr Warren, to the section at
10 the top, where we can read:
11 "Antibiotics not listed in the text may occasionally
12 be prescribed on the advice of a microbiologist or
13 infectious disease physician."
14 I don't know whether that is the section, or not.
15 MR KINROY: I don't think we should waste time on this, but
16 I did note from the evidence that there was a list of
17 additional agents at the end.
18 LORD MACLEAN: I think you mentioned that, Dr Warren?
19 A. I did, indeed, yes. I think most national -- most
20 formularies would recognise that
21 microbiologist/infectious diseases physicians may wish
22 to use the full armamentarium of antimicrobial agents
23 available to them, but some restriction has to be placed
24 on those being generally available to ensure that you
25 have got appropriate agents in particular situations.
1 MR MACAULAY: I am quite happy to return to this, if we can
2 focus on the particular section.
3 I was going to move on to look at another document
4 with you, and that is at GGC21790001. Although this
5 doesn't have a title, I think it is understood to be the
6 Argyll and Clyde drug formulary for 2006, which may have
7 been in use at the Vale of Leven at the relevant time as
8 well. I think --
9 A. I'm not clear about that, because why would that be the
10 case if that hospital was no longer within that patch?
11 Q. Indeed. Let's assume for the moment that it may be of
12 relevance. I think you did have sight of this --
13 I can't remember if you had sight of it when you
14 actually prepared your reports or not?
15 A. No, I didn't. I had sight of it after I prepared my
16 written reports.
17 Q. Again, having looked at it, does it contain within it
18 information that may provide guidance to the clinician
19 in relation to what could be prescribed for what?
20 A. Yes, it does have a section that deals with infection.
21 Q. If we turn to page 156 of the document, we have what
22 looks like a useful table, in that one can look, at
23 a glance, as it were, at various infections and see what
24 is recommended and then what the alternative treatment
25 might be. This is quite a useful presentation.
1 A. I think that is right. Short documents of one or two
2 pages as summaries to larger, more comprehensive
3 guidance are quite commonly used to a national health
4 service, and I think they have a place. The hazard, of
5 course, is that junior staff seldom go beyond them to
6 read the finer print, but the advantage is very
8 Q. If we look to this document, for example, and look at
9 urinary tract infections, can we see here that the
10 recommended treatment, again, we can see, to begin with,
11 is trimethoprim; is that correct? Do we see that in the
13 A. Yes, that is advanced as the first-line agent, which is
14 pretty commonplace. They decline to offer a second-line
15 alternative, relying on antibiotic sensitivities in this
16 document, which is different from the other document we
17 looked at.
18 Q. If we look at page 153, do we have here, again, on one
19 page, advice in relation to the treatment for
20 a community-acquired pneumonia?
21 A. Yes, we do.
22 Q. I think the less severe, if we go down the first column
23 and we come to amoxicillin, adding clarithromycin, as
24 being the first line of choice?
25 A. Yes, I think that is commonplace. Whether it is
1 advisable and whether it corresponds with other
2 formulary advice that I looked at, perhaps we might
4 Q. Again, it is an easy way of seeing what the guideline
5 might be?
6 A. That's right.
7 Q. If we turn to page 146, there is some guidance here
8 given, I think, specifically in relation to urinary
9 tract infections.
10 A. Yes. I think this guidance refers, from my recollection
11 of this document, to infections occurring in the
12 community, and I am not clear that it refers to
13 infections occurring in hospital.
14 Q. Do you mean the guidance about the note:
15 "Amoxicillin resistance is common, therefore only
16 use if culture confirms susceptibility."
17 A. I have no problem with that guidance. All I'm saying is
18 I'm not sure that this would have been promulgated in
20 Q. I see. The point about asymptomatic bacteriuria, is
21 that something that is commonly known and one has to be
22 aware of, if one is prescribing, or thinking of
23 prescribing, for a urinary tract infection?
24 A. I think junior medical staff are often not aware of this
25 entity, and it is quite important to emphasise it, which
1 this document does well. There is a tendency, perhaps,
2 for junior medical staff to regard the reporting of an
3 organism and its antibiotic sensitivities from the urine
4 as perhaps a licence to prescribe an antimicrobial agent
5 without considering whether there are signs of
7 Q. Why do you say that junior doctors might not be aware of
8 this phenomenon?
9 A. Just my common experience, that that is a problem. It
10 depends on their seniors' view, their seniors'
11 supervision of them and their understanding of
12 the situation.
13 I think most junior doctors are aware that almost
14 all patients who have a urinary catheter, after about
15 ten days, will have organisms in their urine without
16 necessarily causing infection, but I am not sure that
17 all junior doctors are aware that the elderly commonly
18 have asymptomatic bacteriuria, for which the evidence on
19 treatment is very thin indeed.
20 Q. Is that down to training, because one would have
21 thought --
22 A. I think it is down to training, yes.
23 MR KINROY: My Lord, I wonder if my learned friend intends
24 to explore in more detail the reason why doctors
25 apparently erroneously treat asymptomatic bacteriuria?
1 Is that the limit of the exploration now, or will there
2 be a revisiting of it later on?
3 LORD MACLEAN: I think, if I follow Dr Warren's evidence
4 thus far, it is a lack of knowledge on the part of some
5 physicians that this condition exists. Am I right in
6 thinking that?
7 A. I think that's right, my Lord.
8 MR KINROY: My Lord, what has puzzled me for some time is
9 that there must be a reason the specimen is taken for
10 testing which leads to the lab results and the
11 misapprehension that what is found in the sample
12 justifies an antibiotic prescription, but it does not
13 come from nowhere. There must have been some indication
14 that the patient was unwell, even if there were no
15 clinical symptoms, I imagine.
16 LORD MACLEAN: Dr Warren?
17 A. I think that is not the case, my Lord. I think
18 specimens are often collected on the initiative of
19 nursing staff, rather than the medical staff. I think
20 there is often a perception that it is necessary to know
21 what organisms are present -- for example, in
22 a catheterised patient -- so that, if the patient
23 becomes unwell, they can be treated.
24 That very easily translates into the scenario I have
25 described, where, when a report comes back, there is
1 a tendency to treat proactively in the hope that that
2 will stop a problem arising with clinical infection, but
3 the evidence for that is very poor and it is likely to
4 select for multiple resistance.
5 I think one can no longer assume, and the
6 microbiologist receiving a specimen can no longer
7 assume, that there is a good justification for taking
8 all specimens. It is not the case. The clinical
9 information that you receive with the accompanying
10 request form is often so brief and so incomplete as to
11 potentially cause you not to know enough as to be able
12 to assess whether or not the patient has infection.
13 DAME ELISH: My Lord, I wonder whether my learned friend can
14 clarify with Dr Warren whether this was commonplace with
15 junior doctors in England and Wales at this time, across
16 the UK, if Dr Warren can --
17 A. Well, it is difficult to know unless you collect the
18 information and you actually ask them. But it is
19 commonplace, when you discuss therapy with them, for
20 them to tell you that they are treating the organisms
21 that are present without necessarily telling you about
22 whether or not the patient has signs of fever, signs of
23 a systemic response, such as a raised white count, or
24 other things. So you sort of have to stop them when you
25 are on the telephone to them and ask about those things.
1 Those would indicate infection. The presence of
2 the bacteria might not.
3 LORD MACLEAN: Dame Elish restricted her question, actually,
4 to junior doctors in England and Wales and, indeed, she
5 went on to say across the UK. Is it commonplace?
6 A. I can't talk about England and Wales because I only
7 practice in one place, but it is common, in my
8 experience, to encounter that situation, so I think it
9 would be reasonable to say that it is commonplace that
10 there is a lack of understanding about this.
11 We have been so concerned about it recently that we
12 have started adding automatic comments to our positive
13 urine reports, making the point that you have to assess
14 whether the patient has infection or not and, indeed, in
15 the later reports that I dealt with for this Inquiry
16 into 2008, I noticed that such became the practice in
17 the Vale of Leven Hospital as well. So I draw from that
18 that this is a universal problem.
19 MR MACAULAY: Just on that last point, are you referring
20 there to the reports from the lab that restrict the
21 number of potential--
22 A. No, I'm dealing with the reports from the lab. It is
23 possible to programme a lab computer to add automatic
24 comments, or you can put them on manually. I noticed in
25 some of the reports -- I think the last report that
1 I dealt with had material from 2009, and I note there
2 that there were automatic comments saying, "You must
3 assess whether the patient has got infection or not,
4 regardless of this report", or words to that effect.
5 MR KINROY: My Lord, I realise the subject is just about
6 completed, but can we have the confirmation of Dr Warren
7 of the surprising idea that samples are taken for no
8 apparent reason, merely as a precaution, to know for the
9 future what bacteria the patient might harbour? That
10 appears to be the evidence.
11 A. I care for, or have cared for, patients in a supra
12 regional spinal injuries unit where all the patients,
13 because they are paraplegic, have catheters. It is the
14 routine practice of the physicians and surgeons on that
15 unit to send me a weekly urine so that I can see what
16 organisms are present in the bladder urine, which is
17 almost always the case, and they take note of
18 the resistances and avoid using agents should the
19 patient become pyrexial and have features of systemic
20 infection. If the organisms present in the urine are
21 resistant to that antimicrobial, that is not an
22 antimicrobial they use.
23 So there you have a systematised system where people
24 are taking samples to look for bacteria and what is
25 present before the patient develops features of
1 infection. It is much more common, I have to say,
2 because it is a readily available body fluid -- if
3 a patient has a catheter, it is much more common to take
4 routine samples.
5 Some laboratories won't examine catheter specimens
6 of urine that are taken from chronically catheterised
7 patients. We take a more benign view and will examine
8 them, as indeed was the case in the Vale of Leven,
9 because you often don't know whether the patient is
10 pyrexial or infected.
11 Does that clarify the matter?
12 MR KINROY: It does, my Lord, yes.
13 DAME ELISH: Sorry, my Lord, if I could indulge
14 your Lordship's patience at this stage. There are two
15 points for clarification: one, would delirium, in
16 a geriatric context, perhaps be a clinical symptom which
17 a junior doctor might identify as associated with a UTI;
18 secondly, is there a test, which I understand may be an
19 MSSU, which can take some days, and might that provoke
20 a doctor into prescribing empirically because, by the
21 time that that test returns, it may be longer and,
22 therefore, present a risk to, particularly, an elderly
23 patient with delirium?
24 LORD MACLEAN: There are two questions there.
25 A. I will try to answer the delirium question first. By
1 "delirium", I mean an acute change in mental state --
2 all right? -- often accompanied by fever. I would agree
3 that that is a symptom of a systemic urinary tract
4 infection, justifying the examination of the urine and,
5 indeed, treatment.
6 That gets slightly changed by some people into
7 consideration of chronic changes in mental state and
8 a patient with dementia becoming a little bit more
9 confused. I think the evidence there is less well
10 established, that, in that situation, you should
11 consider that a urinary tract infection may underlie it.
12 But it is a commonly held belief.
13 The second question, if I understand it, is about
14 the fact that it may be necessary, if the patient has
15 features of infection, such as a raised white count,
16 delirium or fever, to initiate treatment before
17 a laboratory result is available. That is, of course,
18 the case, and treatment may have to be modified, if,
19 when urine is cultured, it then proves that the organism
20 is resistant to the antibiotic first choice used.
21 So it is very common to use a single agent or a pair
22 of agents of wide spectrum initially, to make sure that
23 you don't hit a resistant organism, and very common to
24 have a definitive guideline of what you should then use
25 later on when you have got sensitivities available,
1 perhaps to a number of agents, which agent you should
2 light on for what I would call the definitive treatment
3 of that infection.
4 Of course, if you change your antibiotics, you are
5 exposing the patient to yet another antibiotic, so that
6 has to be borne in mind as well.
7 MR MACAULAY: This particular hare was set running by your
8 comment that junior doctors may not know about
9 asymptomatic bacteriuria, but does supervision play
10 a role, then, in improving that knowledge and ensuring
11 that the junior doctor becomes aware of this symptom?
12 A. I think that is the case. However, I think it is fair
13 to say that, although it is extremely common, urinary
14 tract infection is viewed as a minor infection more
15 commonly than a major one, although it is commonly the
16 source of bacteraemia, particularly in elderly patients.
17 Q. If we go back to the document, page 146, do we see that
18 there is guidance given, again in connection with an
19 uncomplicated UTI, and the suggestion is we have
20 reference to trimethoprim and I think also to
21 nitrofurantoin, and I think you mentioned both of these
22 yourself in connection with this particular --
23 A. Yes, this is good and common guidance. I draw your
24 attention to the definition at the top of uncomplicated
25 UTI, which is "ie no fever or flank pain". So this
1 guidance more materially relates to cystitis, which is
2 often not accompanied by those two, and is an infection
3 of the bladder rather than pyelonephritis, which is an
4 infection that has ascended to the kidneys.
5 Q. If we then leave that particular document aside and move
6 on to another document, this is at GGC21760001, I think
7 you did have this at the time you were drafting your
8 reports; is that right, Dr Warren?
9 A. Yes. I don't recognise the front sheet, but I'm sure
10 I did.
11 Q. I think it is described as the North Glasgow prescribing
12 handbook, but it may be --
13 A. Right, it didn't have a title.
14 Q. No, it doesn't have a title. If we just focus on what
15 we have been talking about, urinary tract infections,
16 and turn to page 37, again we see some guidance given
17 here for urinary tract infections, and the first relates
18 to a lower urinary tract infection. Can we see, again,
19 there is reference to trimethoprim; is that correct?
20 A. That is correct. There is less guidance on the
21 definition of lower urinary tract infection they are
22 using here, in that it doesn't mention the absence of
23 fever and flank pain.
24 Q. But then the alternative given here is co-amoxiclav?
25 A. That's true, and there is a wide variation in what
1 people regard as the second-line agent for lower urinary
2 tract infection.
3 Q. I think in the previous document we looked at for
4 urinary tract infections the guidance was trimethoprim
5 and then the alternative treatment was according to
6 sensitivity? That is broader.
7 A. That is the case. Indeed, we looked in an earlier
8 document and it says trimethoprim or nitrofurantoin.
9 That gives you a measure of the variation.
10 Q. I think one of the other documents that you had
11 a particular interest in was at GGC22180001?
12 A. Yes, indeed. This is a document, again not particularly
13 titled or with days of currency on, but I believe this
14 is a 2007/2008 document, which bids to be a one-page
15 summary of the advice given in the 2007/2008 Greater
16 Glasgow formulary.
17 Q. Again, as you have pointed out, it doesn't have a date.
18 It may be we can date it by reference to what came after
19 this, in 2008, because I think you have also seen that
20 particular document.
21 A. I have, indeed. I would say that this document doesn't
22 differ significantly, in my view, from the advice in the
23 Greater Glasgow formulary, and the antibiotic advice in
24 what they call the therapeutic handbook for 2007/2008.
25 Precisely when in 2007/2008, I can't tell.
1 Q. As you have indicated, it is not dated. Let's just look
2 at some aspects of it. It is headed, just to pick this
3 up, "Infection Management Guideline: Empirical
4 Antibiotic Therapy". That is the title.
5 Just so we can be absolutely clear about this, when
6 we talk about "empirical antibiotic therapy", can you
7 just explain what you mean by that?
8 A. "Empirical antibiotic therapy" is antibiotic therapy
9 that is used when you have diagnosed an infection but
10 you are not aware of what the causative organism in that
11 infection or its antibiotic sensitivities are. It is
12 therapy. There is such a thing as empirical prophylaxis
13 too, which is antibiotics given to prevent infection,
14 again, in the absence of information about what is
15 likely present.
16 Q. Are you in the empirical field before you get the result
17 from the lab?
18 A. Yes, you are. Of course, it is a matter of judgment
19 whether or not the patient needs to be treated for
20 infection at that juncture or whether you can await the
21 result of the laboratory test. I think it is fair to
22 say that, in the 40 years I have been doing
23 microbiology, things have progressed from a situation
24 where you sometimes waited to a situation where you
25 almost never wait, and that has constituted a pressure
1 for labs and for developments of diagnostic reagents to
2 try and speed things up so you make it a little bit more
3 likely. Whether we will ever catch up with the
4 clinician who wishes to prescribe at once, I doubt.
5 Q. If we look at the middle section at the top, there is
6 a heading that reads "Simplify, switch, stop and state
7 duration". Do you see that?
8 A. I do, indeed.
9 Q. "Simplify" is:
10 "Use narrow spectrum agents wherever possible."
11 Is that good advice?
12 A. It is good advice if you assume that the person who is
13 reading the advice knows what is a narrow-spectrum
15 Q. Let's take a junior doctor on the assumption the junior
16 doctor might be first there. Would you expect the
17 junior doctor, with all that training behind him, to be
18 aware of what was a narrow-spectrum antibiotic?
19 A. I think if you question junior doctors about the
20 spectrum of antibiotics -- even middle-grade doctors
21 about the spectrum of antibiotics -- they have, at best,
22 a hazy notion.
23 Q. Against that scepticism, then, can you move on to the
24 next section, which is "Switch". It is quite difficult
25 to read, but it reads:
1 "In the absence of positive microbiology and
2 specific situations (see above) switch to oral therapy
3 when signs of sepsis are resolving and oral route is not
5 There is specific reference to ceftriaxone and oral
6 co-amoxiclav. That, you would say, is an appropriate
8 A. I would make the comment that, unless you are sure the
9 patient is infected in that site, if you are missing
10 positive microbiology after doing microbiological tests,
11 the specimen was taken before the antibiotics were
12 initiated, you have to ask the question whether,
13 certainly in the presence of a C. difficile outbreak,
14 you continue with antibiotics at all. It may be that
15 your diagnosis of infection is wrong.
16 So I think it is reasonable to switch from
17 parenteral therapy to oral therapy, if you can, without
18 broadening the spectre of the agent or disturbing the
19 flora of the patient more, but I think this isn't quite
20 right, if I might put it that way.
21 Q. "Stop", the next section:
22 "Stop: please observe indicated duration of therapy
23 and stop if alternative non-infectious diagnosis is
25 A. I think that is the sort of thing that I am alluding to,
1 a non-infectious diagnosis, and I think it is quite
2 important and, indeed, good practice, to write on
3 a prescription that it is for a limited period. It is
4 commonplace in my hospital to write "For so many days
5 only" when prescribing an antibiotic. It was also
6 commonplace in England at the time -- I can't speak for
7 Scotland -- to have automatic stop orders on
8 antibiotics, such that you would stop the agent,
9 normally after five days or so, and it would be
10 necessary to represcribe it if you wished to continue
11 because there were continuing features of infection.
12 So, yes, I think this is very good advice.
13 Q. Is that, then, a method of reviewing the treatment?
14 A. It is, indeed. It gives pharmacists the opportunity,
15 and nursing staff the opportunity, not to overlook the
16 fact that an antibiotic prescription is continuing, and
17 it means that you have to review it. Depending on just
18 how confident your ward pharmacists are, it may also
19 trigger a referral to a consultant microbiologist if you
20 wish to continue.
21 Q. If we just focus, then, on the urinary tract infections,
22 and we have looked at that in the other documents, you
23 will see it is the third box moving from left to right,
24 and can we --
25 A. The fourth box, I think you mean.
1 Q. Sorry?
2 A. I think it is the fourth box from left to right. You
3 have got it on the screen now. Trimethoprim or
5 Q. We have it on the screen, in any event, "Urinary tract".
6 Can we see here that, for a lower UTI or cystitis,
7 again, trimethoprim is first in the queue?
8 A. And nitrofurantoin, yes, second, matching the document
9 we saw earlier.
10 Q. Then there is some reference to a catheter-related UTI.
11 A. That is the case.
12 Q. We can read on, where we see:
13 "Further antibiotic treatment may not be required",
14 depending on the circumstances?
15 A. Yes, I think that is the case. As I implied earlier on,
16 after ten days of catheterisation, all urine will
17 contain micro-organisms, some of them encrusting the
18 catheter. The advice here is to change the catheter
19 and, hopefully, with your single dose of antibiotic, you
20 may hope that you will reduce the number of bacteria in
21 the urine. I have some doubts as to whether you would
22 eliminate it, but this gives you the idea that you
23 should not automatically prescribe for
24 catheter-associated bacteriuria.
25 Q. Finally, before we leave this particular document, if we
1 move to the left, and just get this section on the
2 screen, so it is the left-hand section of the document,
3 can we see that we are looking at a box that is headed
4 "Lower respiratory tract", and in the box dealing with
5 pneumonia, there is reference to the CURB-65 score as
6 being something that could be used to make an
8 A. Yes, we use this in our hospital, too, I have to say,
9 but despite about ten years of battling on this topic,
10 I find it very difficult -- although junior doctors know
11 what the CURB-65 score is, they find it difficult to
12 write this in the notes or to utilise it to direct their
13 therapy. I don't know why.
14 Q. But is it a method of assessment that has been around
15 for quite some time?
16 A. Yes, indeed, it is. It is well validated and most
17 consultant physicians will know about it.
18 Q. We have looked at that document, which we assume was
19 relevant in 2007/2008. If I can put another document on
20 the screen for you at this juncture, that is
21 GGC06380009. I think this is something you did look at.
22 A. Yes, it is. I believe it corresponds with the second
23 edition of the formulary that I alluded to, produced
24 in August 2008, so after the material period we are
1 Q. I think, in particular, you referred to this in your
2 overview report that we will come to in due course, but
3 there have been some changes introduced to the document
4 which we now assume is post June 2008?
5 A. There have indeed, and I would endorse most of
6 the changes that have been made.
7 Q. Is it possible to have the first document on the screen,
8 we should perhaps get back to that, GGC22180001.
9 I haven't picked this up from you, but if we go to the
10 middle of the document for gastrointestinal, and the
11 section headed "Gastroenteritis", so it is the one on
12 the right, do we see under that heading that it says:
13 "No antibiotic usually required."
14 That is for gastroenteritis. Do we see that?
15 A. Indeed.
16 Q. Then we can read:
17 "If C. difficile suspected, oral metronidazole 400mg
18 8-hourly (after stool obtained).
19 "Second recurrence of C. diff, vancomycin 125mg
21 "Duration ten days."
22 That appears to be the guidance given for C. diff at
23 that time?
24 A. Yes. I think you could perhaps comment on that
25 guidance, if you wish me to?
1 Q. Perhaps you could help us to understand what you take
2 from that guidance?
3 A. Well, the reference to "no antibiotic usually required"
4 is to infectious diarrhoea other than caused by
5 C. difficile, so this would be salmonella infection,
6 campylobacter infection, and other agents that commonly
7 cause community-acquired diarrhoea.
8 I wouldn't say that that guidance applied to
9 C. difficile.
10 The advice to treat on suspicion with metronidazole
11 I think depends on the likely accuracy of that
12 suspicion. I think anybody faced with a white count --
13 a high white count in somebody who has been recently on
14 broad-spectrum antibiotics, develops foul-smelling
15 diarrhoea, you would have a very high index of suspicion
16 that that patient had Clostridium difficile. It might
17 be reasonable to start treatment at that point.
18 But laboratory tests for C. difficile should be
19 available within the working day in most hospitals and,
20 indeed, I think that was normally the case in the Vale
21 and, in fact, they offered an out-of-hours service,
22 which is not something we always offer, although we
23 offer a service at least once in the day for
24 C. difficile.
25 I think if you are going to get a laboratory result
1 back on which you can rely, then you might wait for that
2 laboratory result.
3 The question of when to use vancomycin, the advice
4 here is perhaps somewhat restrictive, even at that time.
5 It was shortly after this that the report in England and
6 Wales, to which I contributed and to which we referred
7 earlier when discussing my CV, was produced, which makes
8 the point that, if the C. difficile infection is thought
9 to be severe, you may embark on vancomycin as the first
10 agent of choice rather than the second.
11 So a degree of qualification about this advice, but
12 I think, in broad terms, it is reasonable.
13 Q. Then, if we look at the other document, that we assume
14 is 2008, GGC06380009.
15 A. Sorry, I think I may be -- ah, yes, okay. I thought we
16 were referring to 2008/2009 in the earlier one. It
17 shows how you can get confused with the similar formats.
18 Here you see what I am trying to summarise, the comment
19 about severe infection and the use of vancomycin early,
20 and I would agree with that.
21 I think the earlier advice was commonplace in 2007.
22 It was commonplace.
23 Q. In relation to urinary tract infection that we focused
24 on earlier, does the advice here appear to be similar to
25 the advice in the previous document?
1 A. Yes, a bit more information is given, so, for example,
2 the use of dipsticks to detect the reduction of nitrates
3 and nitrite in the urine is alluded to. The advantage
4 of a dipstick is that you can do it on the ward. You
5 get an indication of whether there is urinary tract
6 infection. Nitrites is not a particularly sensitive,
7 but quite a specific test for urinary tract infection.
8 DAME ELISH: If my learned friend could perhaps clarify with
9 Dr Warren, when Dr Warren referred to waiting for the
10 result where C. diff may be suspected, are there any
11 dangers in empirical prescription of metronidazole prior
12 to the test, which I think you referred to in your
13 overview report?
14 A. I think -- if you have a period of increased prevalence
15 of Clostridium difficile, you are trying to emphasise to
16 all doctors that they should restrict antibiotic
17 prescription to a situation where they are certain of
18 infection and that they shouldn't use it when they are
19 uncertain of infection, if possible.
20 I think it goes somewhat against the grain to use
21 metronidazole on an empirical basis when you have got
22 rapid laboratory tests available.
23 I think, if you were to use metronidazole
24 empirically, you do run the risk of destroying the
25 anaerobic gut flora whose integrity we believe is
1 essential to preventing C. difficile infection. So
2 providing the clinical context is right, as I alluded,
3 and it is severe, I think it is reasonable to use
4 metronidazole empirically. If the clinical context
5 isn't right, and you were to use it liberally, it might
6 be that you might do more harm than good, although
7 I don't think there is very much published on that.
8 I have to say, in my hospital -- my hospitals, it
9 was not the practice to use empirical metronidazole, but
10 I have noticed that a number of witnesses at this
11 Inquiry feel it is entirely reasonable. I think it is
12 a matter of context.
13 LORD MACLEAN: When you said in that answer -- you made
14 a reference to prevalence. Do you mean within the
16 A. Within, indeed, that ward. If you have five cases of
17 C. difficile already on your ward, there is a high
18 likelihood that you might be dealing with C. difficile
19 and it might be that you were so anxious that you used
20 metronidazole, but you have to bear in mind there are
21 disadvantages. I would say this, wouldn't I, as
22 a microbiologist: I tend to prefer certainty to
23 uncertainty if I can, and then patients don't come to
24 harm. So I like to have a laboratory test available to
1 MR MACAULAY: You mentioned just before we went down this
2 route the dipstick test and how that can --
3 A. On urine, for example.
4 Q. On urine.
5 A. Yes.
6 Q. Would you prescribe an antibiotic on the basis of
7 a dipstick test, in the absence of clinical symptoms?
8 A. I think not. I think you have to be in a situation
9 where you have attributable evidence of infection to
10 justify doing any test and acting on the result.
11 Q. Can I move on and look at some other policies that you,
12 I think, had sight of, and the first of these I want to
13 look at --
14 MR KINROY: My Lord, before we do that, I noticed at page 38
15 of the transcript -- it is no criticism of my learned
16 friend -- the question was:
17 "Question: In relation to urinary tract infection
18 that we focused on earlier, does the advice here appear
19 to be similar to the advice in the previous document?"
20 Of course, there was already a confusion about which
21 document we were referring to, the 2007/2008 or the
22 2008/2009 document. I wonder if he could perhaps take
23 particular care to, in this passage, identify the
24 documents and the periods concerned?
25 MR MACAULAY: I can clarify that if we were to put the
1 documents back on the screen. What we have taken to be
2 the 2007/2008 empirical antibiotic therapy advice is at
3 GGC22180001, and we had, I think, discussed, Dr Warren,
4 the guidance given for urinary tract infection on that
6 The other document that I think we have taken to be
7 2008 onwards --
8 A. Just before we leave that, can I just point out that you
9 are showing the lower urinary tract guidance. There is
10 also guidance on pyelonephritis, which is upper urinary
11 tract infection, a more serious scenario, which is below
13 Q. Since you have pointed that out, can we just go down to
15 A. For pyelonephritis you see the line extends from the
16 lower urinary tract infection, and a different group of
17 antibiotics, including antibiotics given by injection,
18 are included there.
19 Q. So we have oral ciprofloxacin, ceftriaxone and
20 co-amoxiclav as being the options?
21 A. That's right, and both ceftriaxone and co-amoxiclav are
22 given in dosages which indicates that they are for
23 non-oral administration, normally intravenous.
24 Q. The other document was at GGC06380009 --
25 LORD MACLEAN: Which is which?
1 MR MACAULAY: The one on the right we are taking to be 2008
2 onwards, and the one on the left to be 2007/2008.
3 I think the point that I have perhaps not made
4 absolutely clear, I was comparing the advice given for
5 urinary tract infections in the 2008/2009 document to
6 the 2007 document, and I think you said that there was
7 no significant change in the advice?
8 A. There is if you look at the pyelonephritis section.
9 Q. Perhaps we should do that, then. So we have looked at
10 the section for the 2007/2008 document for that, and if
11 we focus then on the section on the 2008 onwards
12 document --
13 A. Now, here you will note under "Pyelonephritis" that
14 there is no longer mention of co-amoxiclav or
15 ceftriaxone; there is mention of a narrower-spectrum
16 agent of amoxicillin combined with gentamicin. Now,
17 gentamicin does not reach the gut flora and disturb it,
18 so it is a very rare associate of Clostridium difficile
19 when compared with ceftriaxone or co-amoxiclav that was
20 in the earlier guidance. I suspect there is not much
21 difference between co-amoxiclav and amoxicillin, but
22 there is a difference between gentamicin and the third
23 generation cephalosporin ceftriaxone.
24 So this document aims to be reactive in terms of
25 reducing the risk of Clostridium difficile by not
1 recommending ceftriaxone.
2 Q. This document, we think, postdated the Vale episode,
3 and, in particular, postdated June 2008.
4 A. I believe that this document was probably issued
5 in August 2008, when the GGC formulary second edition
6 was produced, but, of course, I don't know what was
7 available to clinicians on the wards. I don't know --
8 certainly, when I looked at this document, first of all,
9 I couldn't see any difference, because the format is
10 very similar. It hasn't got a date. I had to look at
11 it quite closely, line by line, before I realised there
12 were these significant differences.
13 We have already heard that there may have been the
14 Argyll and Clyde recommendations still current in the
15 Vale of Leven. I think we simply don't know.
16 Now, it is very important that you have control of
17 documents and you make sure they reach those intended.
18 So, for example, we would try quite hard to have these
19 documents only electronically available, so that, when
20 they cease to be current, they cease to be available.
21 If you have a paper copy and it refers to the previous
22 document, people may persist in giving agents that were
23 not intended to be given at that time.
24 So document control with antibiotics, particularly
25 when there is a period of major change or, indeed, in
1 the change of the organisation responsible for the
2 hospital, is very important. I think the difficulty we
3 have had with these documents might be faced by
4 a clinician, that he wasn't quite sure what advice he
5 was being given.
6 Q. Perhaps we can try to nail this document now, then. If
7 you look at page 1 of this same collection of documents,
8 GGC06380001, we have here an email from Evelyn Forrest
9 that was sent on 22 July 2008 to a number of people, and
10 the subject is prescribed as "Updated antimicrobial
11 guidelines". It begins by saying:
12 "I enclose a self-explanatory document from
13 Scott Bryson which summarises the actions and changes to
14 guidance which have been put in place since the latest
15 concerns and Clostridium difficile."
16 If we turn on to one of the attachments on page 3 of
17 this document, can we read that the first main sentence
19 "Consequently, 6 guidance documents will be
20 implemented with immediate effect, with formal
21 [something] coincide with the new intake of junior
22 hospital doctors on 1st August."
23 The first of these is "Infection Management
24 Guideline: Empirical Antibiotic Therapy". So was it
25 envisaged that -- and the document we have been looking
1 at is attached to this. Was it envisaged that the new
2 intake would be provided with the document when they
3 attended at the hospitals?
4 A. I think this is good evidence of intent. I think, in my
5 experience of issuing antibiotic guidelines, you have to
6 do just more than intent: you have to make sure that the
7 previous documents are withdrawn; you have to make sure
8 that this reaches the nursing staff, particularly the
9 senior ward nursing staff, as was shown in the earlier
10 document there; and you have to make sure that it
11 reaches the medical and surgical consultants. You
12 probably should have discussed it with them -- all
13 right? -- and you almost certainly have to do
14 a presentation to them of the significant changes.
15 I note, if we return to the covering email that you
16 sent, the earlier document, there is actually not much
17 mention there of the senior medical doctors, and I think
18 it's -- I'm just looking for the relevant page. It uses
19 the word "highlight". I have some difficulty with the
20 word "highlight", for the reasons I explained: that the
21 documents were similar in format, and the changes, the
22 significant changes, are not necessarily highlighted.
23 So it is a difficult business, turning around the
24 Titanic of antibiotic prescription in hospitals. It is
25 hard work to avoid colliding with the iceberg. So you
1 have to get out there and very actively change
2 antibiotic policy, if I might put it that way.
3 MR MACAULAY: My Lord, on that sceptical note, perhaps we
4 could rise for some refreshments?
5 LORD MACLEAN: Yes, it is a convenient time to have a break.
6 (11.15 am)
7 (A short break)
8 (11.40 am)
9 MR MACAULAY: Dr Warren, I now want to look at the loose
10 stools policy with you, if we could have that on the
11 screen; GGC00780258. I think this was one of
12 the documents that you were provided with?
13 A. It was.
14 Q. We see it is the loose stools policy effective
15 from March 2004. If we turn to page 259, can we see
16 that it is envisaged that, with a patient with loose
17 stools who could contaminate the environment with
18 faeces, such a patient should be generally placed in
19 a single room?
20 A. We can.
21 Q. If I can also take you to the C. diff policy, and that
22 is at 252 in the same collection of documents, again, we
23 see this is a document that is effective
24 from October 2004, we see that towards the top
25 right-hand side, if we turn to page 254, can we see that
1 under reference to "Accommodation" what is said is:
2 "A risk assessment should be carried out by the ICT
3 to determine if the patient requires isolation nursing."
4 Do you see that?
5 A. I do.
6 Q. "A single room with toilet facilities is desirable"?
7 A. Yes.
8 Q. If we look at the audit tool that is part of this
9 document at page 257, do we see under the heading
10 "Criteria" 1 is:
11 "Patients with CDAD are nursed in a single room with
12 their own toilet facilities/commode."
13 There are other provisions provided as well.
14 A. Yes.
15 Q. If we put the two policies together, the loose stools
16 policy and the C. diff policy, does it seem to be the
17 position that it is envisaged that, by the time the
18 positive result is made available, the patient may very
19 well be in isolation?
20 A. I think that is the burden of these documents. Of
21 course, there are other causes of loose stool, which is
22 not a diagnosis of Clostridium difficile, and it behoves
23 us to consider, one, whether there were enough single
24 rooms and enough commodes and enough fabric, if you
25 like, to encompass both these policies, and also whether
1 there were other conditions that might cause loose
2 stools, of which one is norovirus, for example, which
3 might cause a single room to be occupied even if
4 a C. difficile result is negative.
5 Q. While we have the C. diff policy in front of us, can we
6 see what the treatment envisaged in the policy is for
7 C. diff? This is at page 256. At the section
8 "Treatment", can we see what is being said is:
9 "If possible, discontinue all antibiotics."
10 Would that be good advice, in principle?
11 A. Yes. Indeed, one of the most difficult things to
12 organise, when you are phoning out a C. difficile
13 result, is to persuade clinicians that the response to
14 the metronidazole (a) may be slow, and may be halted,
15 indeed, if they continue with the provocative
16 antibiotics or other antibiotics they are prescribing.
17 Q. Then, looking at the treatment itself, we are told:
18 "Adults: in the first instance, oral ...
19 metronidazole ..."
20 Then we are given the dosage and the duration of
22 A. Yes, this, of course, is guidance written in 2004, so it
23 relates better to the 2007/2008 guidance than the 2008
24 onwards guidance that we have already looked at, in that
25 there is no mention of oral vancomycin here.
1 Q. There is also some suggestion about antibiotic advice
2 being received from the microbiologist or infectious
3 disease physician; is that right?
4 A. Yes. I think it would normally be the situation in
5 England, and even at this stage was the situation, that
6 you would telephone a Clostridium difficile result as
7 a consultant medical microbiologist, and part of that
8 telephone conversation would be a discussion of
9 antibiotic therapy, both for the C. diff and for the
10 avoidance of continuing provocative antibiotics.
11 Q. The other point we can pick up here is the advice is
13 "Do not give Imodium to control diarrhoea."
14 A. Yes, that would apply to any stopping agent for stopping
15 diarrhoea, because the toxin can accumulate. We believe
16 that is a bad thing with C. difficile.
17 I think it is worth commenting, perhaps, too, that
18 there is very specific advice in this guidance that, if
19 oral metronidazole cannot be given, nasogastric PEG,
20 which is a tube into the stomach, or intravenous
21 metronidazole should be given. So there is
22 a consideration of situations when oral metronidazole
23 might not be possible, which is relevant to some of
24 the cases I reviewed.
25 Q. Can we then start to look at some of the cases that you
1 have prepared reports in, and the first of these I want
2 to look at is Alexander McDonald. I will put the report
3 onto the screen. It is at EXP01880001. Do we note from
4 the first page of your report, Dr Warren, that you have
5 noted Mr McDonald's date of birth to be 6 June 1940?
6 A. Yes.
7 Q. If we turn to page 4, you have a section headed "Medical
8 history", and I think you begin by noting that
9 Mr McDonald was admitted to ward 3 of the Vale on
10 29 September 2007; is that correct?
11 A. That is correct. He was admitted with rib pain,
12 confusion and a temperature. He gave a past history of
13 stroke and valvular heart disease.
14 Q. I will look in due course at the medication he was
15 provided with, but do you note on page 5 of your report
16 that he was, on 3 October, transferred to the
17 Royal Alexandra Hospital?
18 A. He was.
19 Q. If we turn to page 6 of your report, have you noted that
20 he was transferred back to the Vale of Leven on
21 10 October 2007?
22 A. That's the case.
23 Q. I think, in relation to this admission, he was
24 eventually discharged on 12 November 2007. I think you
25 note that on page 6; is that right?
1 A. That's the case, after a transfer within the
2 Vale of Leven Hospital on 25 October.
3 Q. The transfer is from ward to ward?
4 A. Absolutely.
5 Q. Was that something you came across in a number of these
6 reports, that there were ward transfers?
7 A. Yes. I think it appeared to me that patients were
8 admitted to either a male or a female medical admission
9 unit ward, which was either ward 3, or I think in
10 association with ward 14.
11 Q. Or ward 6 possibly?
12 A. Yes, ward 6, not ward 14, that's correct. And was then
13 subsequently transferred on to rehabilitation wards or
14 specialist wards. That is a common practice in
15 hospitals these days.
16 Q. Do you then note on page 6, towards the bottom, that
17 Mr McDonald is readmitted to the Vale of Leven Hospital
18 on 11 December 2007?
19 A. Yes. This was an emergency admission with diarrhoea.
20 It is relevant to note that, on 3 December, when he had
21 been going to a day hospital, after his first admission,
22 diarrhoea was actually mentioned in the notes.
23 Q. Perhaps I can just take you to one aspect of the
24 clinical notes. If we look at the medical records at
25 GGC00400027, this is the admission note made for this
1 particular admission. Do we see in the second paragraph
2 that it reads here:
3 "He had a recent hospital admission with
4 a subhepatic abscess which was managed conservatively
5 with antibiotics. Since his discharge, he has
6 experienced 3-4 episodes of diarrhoea daily ..."
7 Would it appear that he had had, on the face of it,
8 a problem with diarrhoea since his discharge from the
9 Vale of Leven?
10 A. That's what the note says.
11 Q. It goes on to say he has been --
12 A. "Feeling feverish", I think, or -- "feverish"?
13 Q. I think what it says is "He has been on and off
14 antibiotics over this period of time", that's the next
16 A. I think there is a specific note elsewhere that, when he
17 came in, he had had cephalexin from the previous day
18 from his general practitioner, but we have no knowledge
19 of GP records of what antibiotics he'd actually been
20 having in that interval. That was not available to me.
21 Q. Was it at this time, when he was admitted, that
22 a specimen was taken and did test positive for C. diff?
23 A. Yes.
24 Q. If we look at the report from the lab, it is at
1 A. Yes, that is the report.
2 Q. We have a specimen collected on the day of admission, on
3 11 December, received by the lab on the 13th and it is
4 a positive result?
5 A. Yes, so there was a two-day delay, apparently, in
6 receipt of the sample.
7 Q. We will look at the treatment in due course, but did he
8 recover sufficiently so as to be discharged from
9 hospital on 21 December 2007? I think you mention that
10 on page 8 of your report.
11 A. Yes, he was discharged on 21 December. I think it may
12 be worth, at this stage, saying that, although we note
13 the date of that report on the laboratory report of the
14 date of receipt, I think there was, in fact, a ward
15 telephone report that suggests that date was wrong.
16 Q. There are two sources, I suppose, we can look at. We
17 can look at the infection control card, and that is at
18 SPF00640001. If we look at the infection control card,
19 I think we see here that the suggestion is that, on
20 13 December, the infection control nurse was informed by
21 the lab staff:
22 "Patient isolated and commenced on oral
24 This certainly seems to tie in with the date of
25 the receipt in the lab, if we go back to that?
1 A. Yes. I can't -- infection control nurses attend
2 hospitals normally Monday to Friday, so I haven't worked
3 out the date, but I would point out that there's
4 a telephone report, which is GGC00400027, of the result
5 of the test.
6 Q. I will just take you to that, then.
7 A. I think it is in the nursing record.
8 Q. Yes, I think we are looking back -- I will come to that
9 and take you to the particular section.
10 Can I then just go back to your report and just
11 understand the layout with this report, and that I think
12 will mean we can perhaps deal with other reports more
14 On page 9 -- and I think this is a format you have
15 followed in your reports -- you summarise the interward
16 and interhospital transfers for this patient.
17 A. That is the case.
18 Q. We can see at a glance what that involved.
19 You also, in this report and other reports, try to
20 develop some understanding in relation to what other
21 patients might have been on the ward at the time or,
22 indeed, prior to the particular patient's admission to
23 the ward to see whether or not there was some connection
24 between the patients; is that right?
25 A. Yes. I think it is fair to say that trying to establish
1 where the infection was acquired is quite important. In
2 many infections, it is not the case that the place the
3 patient was when diagnosed is necessarily the place
4 where an infection was acquired. There were two keys in
5 Clostridium difficile, and ribotype 027, that I found
6 from my own experience prior to the period that we are
7 discussing, which is that it is relevant to look when
8 the patient received antibiotics in the previous 30 days
9 and where they were then, and it is relevant to look on
10 the ward -- which wards they were on prior to the
11 diagnosis in the 30 days, see whether there were cases
12 on the wards at that time, either primarily diagnosed or
13 transferred, as we have discussed and, indeed, whether
14 there were subsequent cases on any of the wards the
15 patient was on and to see whether there was evidence of
17 It is this feature of C. difficile and ribotype 027
18 that I became aware of, really, in the autumn of 2007,
19 that you became aware of a chain of transmission of
20 C. difficile which was unusual and you could track
21 patients and I could track patients in my hospital and
22 trains of transmission.
23 So I have applied this expertise, if you like, that
24 I have gained to this situation generally.
25 Q. You have applied it to each individual case, and it is
1 something I would propose, apart from one case, which
2 I think we can look at particularly, and that is the
3 case of the Fruin ward, which I think is the different
5 You have looked at this in each individual case and,
6 indeed, also, I think, in your overview report; is that
8 A. That is so.
9 Q. So I will come back to this when we look at the overview
10 report, and rather than focusing on the individual
11 cases, apart from the Fruin case, which is different.
12 But in relation to the -- you mentioned the
13 ribotype 027. Of course, so far as this Inquiry is
14 concerned, only a relatively small proportion of
15 the cases were actually ribotyped, and that was later
16 on, from, I think, April onwards?
17 A. I think that is the case. I was trying to illustrate
18 that you can, within periods of increased prevalence,
19 track what is happening to patients. Although in
20 a simple way you might say that C. difficile is acquired
21 when it is diagnosed, I think that is not the case and
22 the antibiotic history is important and knowing what is
23 present in the environment. I think, also, on an
24 individual case basis, you will agree that, if there
25 were other cases on the ward at the time, that must have
1 increased the consciousness of medical staff that
2 C. difficile was around in that environment and, indeed,
3 nursing and probably infection control staff.
4 MR KINROY: My Lord, I wonder if we could clarify that? The
5 witness's realisation of a technique of tracking the
6 course of infection which he acquired in the autumn of
7 2007 is, I infer, particular to him at the time. That
8 would be quite a developed and sophisticated
9 realisation, not necessarily to be found in hospitals up
10 and down the country?
11 LORD MACLEAN: Can you comment on that?
12 A. Of course, one's experience colours one's analysis. It
13 is a well-known medical term, "Unde vene?", "Where have
14 you been?", for infection, and it behoves you, in
15 infection control terms, to consider that Latin tag. It
16 is not just a matter of writing down where the patient
17 is, as an aide-memoire when you are going on your rounds
18 using a T Card system. It is a matter of where they may
19 have acquired their infection.
20 So I think it is a basic premise of infection
21 control and the consultant microbiologist role that you
22 do consider where infection is acquired at the time of
23 diagnosis if you are pursuing infection control matters.
24 MR KINROY: My Lord, I wonder if I may be permitted, that
25 basic premise must be something that the witness had
1 before the autumn of 2007, so the realisation of which
2 he spoke which came to him then must be a more
3 sophisticated and developed one, I take it?
4 LORD MACLEAN: Is that true?
5 A. I think it was not my experience before October 2007
6 that you could track C. difficile in that way, and,
7 indeed, because you lacked the technique of ribotyping,
8 which was used to tell the difference between different
9 strains, it was quite difficult to have an opinion on
11 So I take the point that is being put to me, but
12 I think there was an awareness that there had been
13 outbreaks of Clostridium difficile, certainly in England
14 at the time, and people were acutely aware that they
15 needed to look and see whether there was cross-infection
16 going on with Clostridium difficile at that time.
17 MR MACAULAY: I think you are talking about tracking from
18 ward to ward, but if you have a simple situation, if you
19 have two or three patients in a ward with C. diff, then
20 do you have a problem, on the face of it?
21 A. The answer to that is, perhaps yes, perhaps no. It
22 depends where they have been and where they acquired
23 their diarrhoea. But my very first experience when
24 I was in training in microbiology was an outbreak of
25 salmonella in the hospital that affected five wards.
1 That was very unusual, and I had to look for links.
2 So I don't think it is a particularly unique
3 experience that you have to look for links in cases, and
4 that involves taking a history of where the patient has
6 LORD MACLEAN: Just to clarify, when you said April
7 ribotyping, you meant April --
8 MR MACAULAY: 2008. I think that is the date. Certainly in
9 the latter period, rather than earlier on.
10 A. It was certainly available earlier than that in
11 particular situations. Certainly in England, one of
12 the papers I had read refers to ribotyping being carried
13 out in 2006.
14 Q. Indeed. But I think what I was putting to you was that
15 in the Vale of Leven, in the cases we are looking at --
16 A. Oh, yes. That was done, I think, pretty much in
17 retrospect in April 2008. I accept that.
18 Q. I think you are also aware that -- I think you have been
19 made aware of this information -- although you have had
20 quite a number of cases to look at, namely, 19, there
21 are others who are looking at all the cases from this
22 perspective to see what connections, and so on, can be
23 made between the 60-odd cases I think that we are
24 looking at.
25 A. I think that's right.
1 Q. In particular, Professor Duerden I think is looking at
3 I will return to this when we look at your overview
4 report. In the meantime, can I take you to page 12 of
5 your report, where you are now reviewing the antibiotic
6 treatment that Mr McDonald had, in particular during his
7 first admission to the Vale of Leven Hospital?
8 In the first couple of paragraphs you make reference
9 to the guidelines that we have already looked at, and,
10 again, I think, just to look at this now, because it is
11 a format you use in all your reports, that is what you
12 are doing, you are setting out the background under
13 reference to the guidelines before you look at the
14 actual case?
15 A. Yes, that is right. I was not aware at the time of
16 the Argyll and Clyde guidelines, but I think I have
17 explained that I don't think those should have been the
18 measure of what was going on at this hospital at the
20 Q. So if we then turn to page 13, have you listed the --
21 particularly the antibiotics that Mr McDonald received
22 towards the top of the page?
23 A. I have, as far as I can extract them from the notes.
24 Q. You have just touched upon this already, but you say in
25 that first main paragraph after the list that it is
1 generally agreed that provocative antibiotic
2 prescription can precede C. difficile, usually by up to
3 30 days and possibly by longer. Is that right?
4 A. That's right. That is derived from the definitions that
5 are applied as to whether or not cases are truly
6 community-acquired or relate to a period of
7 hospitalisation if they are diagnosed in general
9 The guidelines there, I think, to be precise, are,
10 if it occurs in the community within 28 days of
11 hospitalisation, to which I have added a couple of days'
12 latitude, to give 30, then it should be regarded, as in
13 this case, as hospital-acquired but
14 community-associated -- sorry, community-diagnosed but
16 MR KINROY: My Lord, I wonder if this might be --
17 A. Community-diagnosed, so diagnosed in a patient who comes
18 in from the community, within three days of admission;
19 but hospital-acquired, in that it relates to a period of
20 up to 30 days during which he was in hospital preceding.
21 Now, some authorities consider that there is
22 a further period of uncertainty of up to eight weeks
23 after that, which may also be relevant to hospital
24 acquisition, but in my experience, and in my experience
25 in the cases I have reviewed all bar one, it is not
1 necessary to go back that far. A 30-day antibiotic
2 prescription is what you are normally talking about.
3 MR MACAULAY: Just to clarify one point that you made there,
4 when you talk about community-diagnosed, I think, in
5 fact --
6 A. He was diagnosed in hospital.
7 Q. In hospital.
8 A. But he had come in with the diarrhoea, and it is
9 a general rule that is applied in infection control,
10 that, if you have only been in two days -- and you give
11 a little bit of latitude to getting the tests done --
12 you are dealing with a community-onset infection.
13 Q. So it is community-onset, but hospital-acquired?
14 A. Exactly so.
15 Q. You tell us towards the bottom of page 13 that, although
16 the GP had prescribed the cephalexin the day before
17 admission, you don't consider that played a role as
18 being a provocative antibiotic because of the timescale?
19 A. No, but, of course, I have no knowledge of the other
20 antibiotics we have alluded to that might have been
21 prescribed in general practice.
22 Q. Can we then look on page 14 at the antibiotic treatment
23 that Mr McDonald received in that admission
24 in September 2007? You tell us towards the top of
25 the page that he received co-amoxiclav and also
1 clarithromycin. Can you tell us, from what you took
2 from the records, why it was that these antibiotics were
3 being prescribed?
4 A. I think, when he was initially admitted -- and it was
5 considered that he probably had a pneumonia, because he
6 was complaining of pain in his ribs, which might have
7 been pleuritic in nature. At that stage, they did a CT
8 scan, and I think they changed their diagnosis to one of
9 an abscess surrounding his colon below the liver,
10 a so-called subhepatic abscess.
11 Q. Do I take it from that that the co-amoxiclav and the
12 clarithromycin you thought were being prescribed for
13 a pneumonia, in the first instance?
14 A. Yes, in the first instance. I think that was their
15 working diagnosis and their empirical prescription.
16 Q. Was that a reasonable approach?
17 A. Yes, not unreasonable, I think.
18 Q. Then, if we turn to page 15, you here mention at 3 and 4
19 metronidazole and levofloxacin. Now, can you tell us
20 why that combination was prescribed on 1 October?
21 A. Well, the metronidazole -- obviously, if you are dealing
22 with -- well, no, not obviously. If you are dealing
23 with an infection that may involve the colon -- all
24 right? -- you have to consider anaerobes may be
25 a contributing part of that.
1 Now, although co-amoxiclav has a reasonable
2 anaerobic spectrum, most people, for an anaerobic
3 infection, would use metronidazole.
4 So I think it was added for that reason. Now,
5 whether that was necessary is difficult, but I would
6 agree that metronidazole would commonly be used in that
8 The levofloxacin is a more unusual addition, I would
9 say. It's not my normal practice to advise using
10 a quinolone in that scenario, but maybe the patient was
11 unwell enough to justify broadening out the spectrum of
12 co-amoxiclav, which, as well as including anaerobes, as
13 I have alluded to, also covers other members of
14 the colonic flora.
15 I would have expected, perhaps, that the
16 co-amoxiclav and the clarithromycin might have been
17 stopped, in favour of moving to the levofloxacin and
18 metronidazole, but, in fact, when you look at the
19 record, you will find that levofloxacin and co-amoxiclav
20 were given together, which is perhaps two antibiotics
21 where one would do.
22 Q. What about the guidelines here? Did they cover this?
23 A. I don't think the guidelines cover this scenario, which
24 is an unusual scenario of an abdominal abscess or
25 abdominal inflammation that you feel you cannot operate
1 on and that you are going to treat conservatively with
3 Q. Just to be clear, then, in relation to the use of
4 the levofloxacin, in the circumstances, do you consider
5 that that was appropriate or not?
6 A. I would have been tempted, in that situation, to give
7 different antibiotic advice and not to use an oral
8 quinolone. I tend to use, and have from before this
9 episode tended to use, gentamicin, which is an
10 intravenous antibiotic which doesn't affect the gut
11 flora, with penicillin and metronidazole if I think
12 there is gut-associated sepsis.
13 Q. Coming back to the question, then, what is your opinion:
14 do you consider --
15 A. I have used the related quinolone antibiotic
16 ciprofloxacin in these situations, but with some degree
17 of caution and for a short period of time.
18 Q. So in this case, the levofloxacin was used from
19 1 October to 21 October, that is for about 20 days?
20 A. I regard that as a long period of time and I wouldn't
21 have used levofloxacin for 19 days.
22 But I would emphasise that this lies outside the
23 period of 30 days when he presented with his initial
24 description of diarrhoea, I think.
25 I think the levofloxacin was stopped on 21 October
1 and the first mention we have of diarrhoea is
2 3 December.
3 Q. Yes. I think, if I can go back to -- he was, I think,
4 discharged on 12 November, and the suggestion in the
5 medical records was that he had had diarrhoea since --
6 A. I accept that. It is imprecise when he had the
7 diarrhoea, but that is in his admission note, I agree.
8 So, in which case, it would have been relevant.
9 So I regard the prolonged period of levofloxacin as
10 probably avoidable and not a good choice.
11 Q. Can you see, from what you have read in the records, any
12 basis upon which it could be said that it was an
13 appropriate antibiotic to use for that period of time?
14 A. It depends on your evaluation of whether he had
15 continuing infection or not. But a prolonged period of
16 an oral quinolone is not something that, in this
17 situation, I would be inclined to use.
18 Q. Let's leave that at that and move on to page 18 of your
19 report, where the next antibiotic you look at is the
20 cefuroxime, which was prescribed from 4 to 6 October.
21 What about that? As you say, it was given concurrently
22 with the levofloxacin and the metronidazole?
23 A. Yes. I think -- there was no reason given in the notes
24 for the prescription of this agent. I think it would be
25 fair to say that cefuroxime has a slightly broader
1 spectrum of activity, perhaps, than levofloxacin against
2 Gram-positive organisms, but then not a very different
3 spectrum against Gram-positive organisms from
4 co-amoxiclav. So, again, my comment would be,
5 "Either/or; perhaps not both".
6 Q. I think what you say in your report is it seemed to be
7 an unnecessary prescription?
8 A. That's the case.
9 Q. Is that your view?
10 A. That's my view.
11 Q. Then the fifth antibiotic I think you mention is the
12 co-amoxiclav from 6 to 19 October.
13 A. Yes.
14 Q. Again, that would, I think, coincide with the
15 metronidazole and the levofloxacin. What about that?
16 A. Something there is unnecessary. I mean, I think, in my
17 experience, co-amoxiclav might be used in that
18 situation, probably not the metronidazole or the
19 levofloxacin, but it is difficult to evaluate severity
20 and what is going on in the notes. So, again, it might
21 be an either/or scenario, rather than an
22 all-three-together scenario.
23 Q. If we go back to page 17, I think I have missed that,
24 you say towards the bottom at paragraph 5 that from 1 to
25 2 October intravenous vancomycin was also being given.
1 Was that necessary here?
2 A. I don't think it was necessary in this situation.
3 I mean, vancomycin is perhaps -- although regarded as
4 a narrow-spectrum agent by some, it has the broadest
5 spectrum of activity against Gram-positive organisms.
6 But I can't see there was any evidence of therapeutic
7 failure that justified broadening out the spectrum of
8 what they were already using in the way of Gram-positive
9 agents. It covers enterococci, but then co-amoxiclav
10 covers 90 per cent of enterococci too.
11 I think there was a lot of changing of antibiotics
12 here, but it is not clear to me why that was the case.
13 It is, I think, not evident why the antibiotics were
14 being changed.
15 Q. Then, when we come to the admission of 11 December, when
16 the diagnosis was made, have you noted that he was
17 prescribed intravenous gentamicin and also the
18 intravenous vancomycin? What was the thinking behind
20 A. Well, this gentleman, as I alluded to, when he was
21 admitted, had valvular heart disease. One of
22 the complications of valvular heart disease and
23 infection is that the infection can light on the heart
24 valve. That is a severe and sometimes life-threatening
25 infection. Vancomycin and gentamicin would be
1 a broad-spectrum choice of agents that would cover
2 infective endocarditis. So although they had no
3 evidence of vegetations on the heart valve that would
4 suggest that infection, an unnamed microbiologist gave
5 advice that that was appropriate systemic antibiotics.
6 I don't think they would have contributed to his
7 C. difficile in any way because neither of those
8 antibiotics reach the colon. So I think it was quite
9 good advice for somebody who was severely ill where the
10 possibility of endocarditis existed, while they were
11 awaiting the results of blood cultures.
12 Q. If I take you back to page 18, section 7, where you are
13 dealing with the co-amoxiclav, I think we have discussed
14 that, but you end up by saying, and we have your views,
15 but you also say, I think, that this lies outside any
16 guidelines you have looked at; is that correct?
17 A. Yes, I think that is the case. This is a complex case.
18 Q. Turning to page 19 of your report, about halfway down,
19 your paragraph beginning, "These antibiotic levels were
20 poorly monitored, in that there is no record they were
21 telephoned or an interpretation provided by the
22 microbiologists as to further dosing", what do you mean
23 by that? Is that the vancomycin and gentamicin you are
24 talking about?
25 A. That is the vancomycin and gentamicin. I mean, the
1 control of both of those is important, particularly with
2 gentamicin, on grounds of toxicity as an agent, and
3 vancomycin in terms of efficacy; all right?
4 It is important that you measure the levels and see
5 whether the patient is handling those antibiotics in the
6 way you would expect, for example, and I think this
7 patient had an element of renal impairment which might
8 affect the excretion of this antibiotic. So to avoid
9 toxicity and get the dosage right, you monitor levels.
10 Now, when you monitor levels, you need to take the
11 serum for the antibiotic level at a specified time after
12 the dose, and a microbiologist, to give advice, needs to
13 know the time of the last dose and the time the specimen
14 was collected and then they can give advice on the
15 appropriate dosing and the appropriate repetition of
17 I didn't see any evidence in the reports that that
18 was what went on. There was no reporting back of
19 the times of the last dose. I'm not sure, therefore,
20 that the microbiologist could have been expected to
21 issue helpful advice on the dosage.
22 Q. If we move on to page 20, and I will discuss this with
23 you now because, again, it is a presentation that we
24 will see in all your reports, and I will take it from
25 you now, rather than repeating it, you introduce the
1 table that we see on page 20 by saying:
2 "The risk of C. difficile needs to be considered
3 when prescribing antibiotics in a period of increased
5 You then go on to give some information about your
6 own studies in connection with a particular series of
7 record linkage of pharmacy antibiotic prescribing. Can
8 you explain this presentation to us?
9 A. An awful lot of perception of the role of antibiotics in
10 causing C. difficile is based on impressions gained from
11 the published literature at various times, but there is
12 a dearth of information about how this applies in 2007
13 and currently.
14 Because, in my hospital, all antibiotics prescribed
15 are transcribed into a database by the ward pharmacist,
16 I am able to look at how many patients received an
17 antibiotic -- all right? -- in a given time period, and
18 also, by linkage, how many of those developed
19 C. difficile.
20 This I can do either by the antibiotic prescription,
21 and we must remember that the same antibiotic may be
22 prescribed more than once, or on a patient basis.
23 So I refer here to "% scripts", which is percentage
24 prescriptions, or "% patients".
25 What I have done here is I have looked at periods of
1 increased prevalence, such as occurred in my hospital in
2 2007, and periods later on, where we have got control of
3 the situation and C. difficile rates have fallen, and
4 I am looking here at, in the first figure, the period --
5 the first figure in each box of the table, the period
6 when we had high prevalence of C. difficile, and the
7 second figure in the box is a period of low prevalence,
8 and the point I am making is that you can be
9 quantitative about the percentage of patients that are
10 going to get C. difficile, and it may come as a modest
11 surprise to some members of the audience that
12 C. difficile is a relatively rare event in antibiotic
13 prescribing, and people's perception of when
14 C. difficile occurs may not be the same as the objective
15 facts when you look at it.
16 Of course, there are confounding factors in this
17 data, so patients may receive a number of antibiotics,
18 and I have not tried to separate out in this particular
19 tabular presentation where they received one antibiotic
20 alone, because that is not the real situation. About
21 80 per cent of patients with C. difficile receive at
22 least two antibiotics and, if you like, C. difficile
23 will then appear twice in this situation. So the
24 denominator will be different because it will be
25 specific to the antibiotic, but if a patient receives
1 two antibiotics, it will appear in both boxes for the
2 two different antibiotics.
3 Q. Can we just take an example, just to understand this.
4 If we take the co-amoxiclav, which is the first
5 antibiotic --
6 A. Okay. Let me run across the line for you. So, in
7 a period of high prevalence in my hospital, 0.8 per cent
8 of prescriptions for co-amoxiclav were followed by
9 C. difficile; in a period of low prevalence, that falls
10 to 0.3 per cent.
11 If we look at it on a patient basis -- obviously,
12 with what I said about repeated prescriptions, if you
13 look at it on a patient basis, then the incidence goes
14 up a little bit: hence 0.9 per cent, rather than
15 0.8 per cent.
16 Q. Can I understand this: does this assist us in telling us
17 which of these antibiotics, in your sampling, bearing in
18 mind that we are not just looking at the one, there may
19 be others involved, was the most provocative?
20 A. That is the intention of the table. So providing you go
21 down a particular column, and provided you stay either
22 in a period of high prevalence or a period of low
23 prevalence, you can compare those figures.
24 Now, you have to interpret them with care, but let
25 me just light on an example: cefuroxime there in the
1 first column, in a period of high prevalence,
2 2.9 per cent of prescriptions of cefuroxime were
3 followed by C. difficile, compared with co-amoxiclav,
4 interestingly, 0.8 per cent.
5 Q. So that tells me -- correct me if I am wrong -- that in
6 your series the cefuroxime was more provocative?
7 A. That's the interpretation I would incline towards.
8 Obviously, you have to be wary of the numbers -- all
9 right? -- but there were quite a lot of cases, more than
10 2,000, involved in this record linkage. I think it is
11 reasonable. But you do have to also be aware that there
12 were confounding -- this confounding factor of
13 the patient receiving other antibiotics.
14 Q. If we take metronidazole, for example, where we see it
15 is at 1.3 per cent, but that patient may very well have
16 been receiving one of the other antibiotics as well?
17 A. Exactly so. So, for example, if they were receiving
18 cefuroxime with the metronidazole, you are looking, in
19 the metronidazole figure, at a figure that is affected
20 by the commonality of prescribing two agents together.
21 So it is a blunt tool, but it gives some impression.
22 Vancomycin here is given about the same rate as
23 ciprofloxacin, but that is because the agents are often
24 prescribed together in my hospital.
25 Q. Is this something that you have published, or is it
1 simply something that is personal to you?
2 A. It is something I am preparing for publication.
3 MR KINROY: My Lord, I wonder if we could just ask if the
4 statistics here may depend upon local resistance in the
5 witness's own hospital?
6 A. I think that is probably unlikely. It is thought, and
7 only thought, that the provocative action of
8 the antibiotics in creating C. difficile is because they
9 affect the gut flora, and particularly the anaerobic
10 elements of the gut flora, the so-called bacteroides
11 species. Of course, it is possible, if you have a very
12 antibiotic-resistant gut flora, that nothing much in
13 antibiotic provocation terms affects the flora, but
14 I don't think there is any evidence on that point.
15 So, as you will see as you go through some of these
16 things, people's assumption about what is associated
17 with C. difficile may not be borne out by the facts. So
18 I am trying to apply the scientific basis of
19 observation -- all right? -- of what actually has gone
20 on in my experience, in terms of antibiotic provocation
21 of C. difficile, rather than transplanting it from the
23 MR MACAULAY: We know, I think, from what we have already
24 heard, that it is recognised generally that
25 broad-spectrum antibiotics are seen to be more
1 provocative for C. diff, but as a matter of general
2 understanding, that is the position?
3 A. Yes, but you have to define what you mean by
4 "broad-spectrum". I mean, I think probably only
5 penicillin and flucloxacillin and metronidazole -- and
6 even metronidazole is arguable -- I would regard as
7 narrow-spectrum. Almost all other antibiotics in use,
8 of which I think there are 78 in the British National
9 Formulary, can be regarded as broad-spectrum in some
10 degree. It really depends on an individual antibiotic
11 relationship to C. difficile.
12 Q. Can we then look --
13 MR KINROY: My Lord, if I may ask one further last question:
14 these statistics do not concern monotherapy. In each
15 case, the statistic concerns the antibiotic in
16 combination with, one infers, at least one other
17 unspecified antibiotic.
18 A. Not necessarily. They are the antibiotic prescriptions
19 recorded in the hospital, which may be alone or
21 I am afraid, although I tried, my computer is not
22 powerful enough to actually provide the information on
23 the ones alone, although, in my overview report, I do
24 address a situation where I prospectively looked for
25 sole antibiotics as provocative factors.
1 LORD MACLEAN: Over what period?
2 A. These are years.
3 LORD MACLEAN: Which?
4 A. These are years. Antibiotics alone, I was looking 2003
5 to 2006; I was then looking 2007, I think, if my memory
6 serves me, to 2008; and then a subsequent period.
7 So I have looked over a number of periods. To look
8 at that in detail is perhaps not appropriate in the
9 middle of this case, but the comment I would make is
10 that the rank order of which antibiotics provoked
11 C. difficile is broadly in accord with what is described
12 in the literature. So third-generation cephalosporins
13 very commonly provoke C. difficile; metronidazole and
14 vancomycin relatively rarely; benzyl pen less rarely
15 than amoxicillin.
16 So although the prevalence affects the actual
17 percentage -- all right? -- presumably because, if an
18 organism is highly prevalent, it means it is around in
19 the environment and, therefore, can cross-infect
20 patients, the actual chances of provocation probably
21 depend on the properties of the antibiotic themselves.
22 Q. Can we then look at your review of the diagnosis --
23 MR KINROY: My Lord, I did say it was one last question, but
24 might I ask another, which is: it would be surely wrong
25 to conclude from this table that anything except the
1 rank order, and it would be wrong, in particular, to
2 conclude, for example, that vancomycin is twice as
3 likely to provoke C. diff illness as co-amoxiclav?
4 A. You have to understand the data. You have to know about
5 my hospital. So I would agree with your question. All
6 I am saying is that C. difficile is a relatively rare
7 complication of antibiotics, which I think this data
8 does demonstrate and, when you are trying to decide
9 which is the provocative antibiotic, you have to bear in
10 mind that the figures are quite close to each other.
11 There are some that are regularly higher, and some that
12 are regularly lower, so rank order is relevant, I would
14 MR MACAULAY: This is something you will publish and no
15 doubt those who are interested in it will look at it.
16 A. We might look at it perhaps under the overview report
17 briefly, perhaps.
18 Q. If I can move on, though, and look at your review of
19 diagnosis and treatment for C. difficile, I think, as
20 I think you already indicated, in fact, Mr McDonald's
21 infection you consider was community-onset, but
22 hospital-acquired; is that correct?
23 A. That's correct.
24 Q. In relation to the treatment, then, for that, the
25 treatment that he was given was -- what have you noted?
1 A. He was given metronidazole, which, as we have seen from
2 the guidelines, was the first port of call in terms of
3 treating C. difficile, and he made a very good response
4 to that.
5 Q. You tell us on page 23 that you consider that there was
6 a prompt diagnosis of his C. diff on admission to
8 A. Yes, I did think this, and we have discussed the issue
9 of telephoned reports, of when clinicians on the ward
10 were told that the patient had C. difficile and told the
11 results of tests. As is commonly the case if you don't
12 issue interim reports, the telephone report was
13 consistently earlier and usually the same day as receipt
14 of the sample.
15 DAME ELISH: On that specific point, my Lord, it has come to
16 my attention that earlier, when we were discussing the
17 timing of the phoned report, the suggestion was made,
18 perhaps, that it was the 13th. I wonder if my learned
19 friend could refer back to the request form, which
20 hasn't been put on the screen? There is an annotation
21 at the side which I wonder if Dr Warren could look at,
22 which might suggest, in fact, it was telephoned to the
23 ward on the 12th rather than the 13th.
24 A. I haven't normally seen the individual request forms,
25 obviously, because they are not in the notes, my Lord.
1 MR MACAULAY: I think you did say you had noted from the
2 nursing notes there was a call on -- did you say the
4 A. I'm not sure, without looking at it, whether it was the
5 11th or the 12th, but it was certainly earlier than the
6 written report. It is important to understand how labs
7 work. You may conclude other work on a faeces sample
8 which holds reports back because culture takes longer
9 for some other organisms, but you would expect
10 a C. difficile report to be telephoned as soon as that
11 result became available.
12 LORD MACLEAN: The infection control nurse was informed on
13 the 13th, I think. That's what we saw.
14 A. That's what we saw written on the card. I don't know
15 whether the 13th is a Monday or Sunday. I haven't got
16 my diary available. But she might be reported to on
17 a Monday if a sample was processed on the Sunday, for
19 MR PEOPLES: My Lord, I think it was a Thursday.
20 LORD MACLEAN: Have you got the expert with you?
21 MR PEOPLES: I have the expert with me on dates.
22 A. You understand my difficulty.
23 MR PEOPLES: Yes, it was a Thursday, I'm told.
24 LORD MACLEAN: Which, the 13th?
25 MR PEOPLES: The 13th.
1 LORD MACLEAN: I think I'm right in recalling that the
2 infection control card shows that the nurse was involved
3 on the 13th.
4 MR PEOPLES: The infection control nurse records that she
5 was informed by the lab of the results, although she
6 does talk about them being positive. Yes, I think it is
7 correct that the infection control nurse records in the
8 infection control card that the lab informed her on the
9 13th, Thursday. I think she refers in the card to the
10 positive date being the 11th, but I'm not sure what one
11 can take from that.
12 LORD MACLEAN: I think we know it was collected on the 11th.
13 Is there any other record?
14 DAME ELISH: My Lord, GGC23460030, which is the nursing --
15 sorry, the request form, I should say. There appears to
16 be an annotation in handwriting at the side which
17 indicates "5 pm, 12 December", there is an initial and
18 "ICN" ticked and "IDU" ticked.
19 MR MACAULAY: Perhaps we can put that on the screen, then,
20 since my learned friend has raised it. Can we have
22 DAME ELISH: On the right-hand side, my Lord.
23 A. Okay. Now, you will note that the typed report in the
24 notes says that it was received in the lab at 0855 on
25 13 December, which is after the test is actually carried
1 out and telephoned. So there is obviously a problem
2 with the date received that is logged on the computer.
3 MR MACAULAY: But can you work out this, then, from this?
4 When does it bear to have been telephoned to the ward?
5 A. I found somewhere a nursing telephone report.
6 Q. I have been looking at the nursing notes and haven't
7 found it.
8 A. Okay. Well, I haven't got a reference, so maybe it is
9 not the case.
10 Q. I will take you, for example, to page 129 -- perhaps
11 before we leave the receipt form, I am still trying to
12 work out where we have a note to tell us that this was
13 telephoned to the ward.
14 A. I have said in my report that it was presumptively
15 a telephone report of testing the same day, but
16 a misregistered date of receipt in the lab. There was
17 certainly a misregistered date of receipt in the lab,
18 because we have evidence that the test was available one
19 day earlier, but I can't quote a reference on when it
20 was telephoned to the ward.
21 Q. If we look at the right-hand side of what is on the
22 screen, it suggests "Phoned ward"?
23 A. Yes, on the 12th.
24 Q. At 5 pm on the 12th.
25 A. So a one-day delay. Interestingly, I note that the
1 faeces sample on the laboratory report is recorded as
2 being collected at 2200 on the 11th; all right? So if
3 it was not transmitted on call and the oncall technician
4 called out, that would have been processed in the
5 following day's batch, which ties up with what is
6 written on the request form here, with a report on the
8 Q. It may be, then, that the ward were told on the 12th at
9 5 pm, by which time the infection control nurse might
10 have left?
11 A. Yes.
12 Q. I think this has been triggered by the comment you made
13 on page 23 of your report, that you consider that the
14 diagnosis was promptly made?
15 A. Yes, I think so. I think if you take a sample overnight
16 and it is processed the following day, that is entirely
18 What it does highlight, my Lord, perhaps, is that
19 one has to be careful about the date of receipt on the
20 laboratory reports. If you look at the process of
21 registering samples, the date of receipt is meant to be
22 recorded, but if you hit the "F10" button on your
23 computer, it defaults to the current date.
24 So if somebody was going at speed and hit the "F10"
25 button, the wrong date might get on a record.
1 Q. We have certainly seen --
2 A. I think you have seen examples of that elsewhere.
3 Q. -- that in other cases.
4 Finally, if we turn to your conclusion in
5 Mr McDonald's case on page 25, you mention the
6 provocative antibiotics that were given during the first
7 admission, and I think you say that the infection was
8 acquired in hospital. You leave open whether or not it
9 was the Royal Alexandra Hospital; is that correct?
10 A. Well, I have no information on what was going on in the
11 Royal Alexandra Hospital at the time, in terms of cases
12 that might indicate whether there was a source there or
13 not. So it is very difficult to evaluate, in this case.
14 When I looked at the Vale of Leven situation, there
15 were antecedent cases in some of the hospital wards, so
16 it is a possibility that it was Vale of Leven acquired;
17 it is a possibility, equally, perhaps, that it was in
18 the RAH. I can't decide.
19 Q. If we remind ourselves of the history, he was admitted
20 to the Vale of Leven on 29 September, and then
21 transferred to the Royal Alexandra Hospital on
22 3 October 2007 --
23 A. Yes.
24 Q. -- but then back in the Vale on 10 October. He spends
25 a week in the Royal Alexandra Hospital in early October?
1 A. Yes.
2 Q. He then spends over a month in the Vale?
3 A. So it is more likely that you are dealing with the Vale,
4 I think. I think that is fair. But it is possible.
5 That, of course, affects where you think the relevant
6 bit of exposure was when he was on antibiotics, which he
7 was for a prolonged period.
8 Q. The next case I want to raise with you is Julia Monhan.
9 We have your report here, Dr Warren, at EXP01980001.
10 I think we see from the front page of your report that
11 Mrs Monhan was born on 19 October 1927; is that correct?
12 A. Yes, she was 80 years old at her admission.
13 Q. If then we look at the medical history at that time,
14 that is at page 4 of your report, do you note here that
15 Mrs Monhan was admitted to the Vale of Leven on
16 5 December 2007?
17 A. She was, briefly, admitted with diarrhoea that was
18 thought to be infectious. She was admitted from the
19 nursing home.
20 Q. Was a sample taken and did that prove to be a negative
22 A. That is the case. That was reported after she was
23 discharged from hospital.
24 Q. She was discharged on 7 December?
25 A. That's right.
1 Q. If we turn to page 5 of your report, have you noted that
2 on 11 December 2007 a sample was taken when she was
3 still in the community; is that right?
4 A. That's right. It was taken in the nursing home. She
5 had been prescribed antibiotics -- and we may return to
6 that -- when she was first admitted, so a sample was
7 sent in from general practice which proved to be
8 C. difficile positive.
9 Q. Perhaps we can look at the report of that at GGC --
10 LORD MACLEAN: Mr MacAulay, could we rise now? There is
11 a reason for that.
12 MR MACAULAY: Yes, indeed, my Lord.
13 LORD MACLEAN: Could we sit again at 1.45 pm? It is only
14 12.50 pm now.
15 (12.50 pm)
16 (The short adjournment)
17 (1.45 pm)
18 MR MACAULAY: Good afternoon, Dr Warren. Just before the
19 break, I was going to put on the screen the lab report
20 for the positive specimen for Mrs Monhan. If we look at
21 GGC27240005. We noted before the break that Mrs Monhan
22 tested positive when she was in the home. We can see
23 that -- this is in a different form to what you are used
24 to. But can we see that the note collection time is
25 given at the top, but the reporting time is
1 13 December 2007, and this is a positive result?
2 A. Yes.
3 Q. This, I think, pre-dated Mrs Monhan's subsequent
4 admission to the Vale of Leven on 21 December 2007; is
5 that right?
6 A. Yes.
7 Q. Just looking to page 5 of your report, and that
8 particular admission, have you noted in the fourth line
9 down that the patient is said to have just completed
10 a course of antibiotics for C. diff and is said to be
11 incontinent of foul-smelling faeces?
12 A. Yes.
13 Q. So she was diagnosed with recurrent C. difficile
14 infection; is that the position?
15 A. Yes, I think that is right.
16 Q. After treatment, was she discharged fairly shortly after
17 that, on 29 December 2007?
18 A. Yes, she was discharged to finish a course of
20 Q. Just to remind ourselves of the position here,
21 Mrs Monhan had a short admission to the Vale of Leven
22 from 5 December to 7 December, during which time she was
23 negative for C. diff?
24 A. That is correct, yes.
25 Q. But during that time, she was prescribed with
1 ciprofloxacin, and I will look at that in a moment.
2 A. That's fine.
3 Q. She was then tested positive in the community and
4 readmitted to the Vale of Leven on 21 December 2007?
5 A. That's correct.
6 Q. She was in hospital for about a week and then
8 Really, two points I want to raise with you in
9 connection with this case. The first relates to the use
10 of ciprofloxacin. If I can take you to page 12, first
11 of all, of your report, you say in the second paragraph:
12 "The only antibiotic therapy recorded in this
13 patient's history that may have provoked C. difficile is
14 the prescription of ciprofloxacin for a putative
15 diagnosis of infectious diarrhoea on 7 December 2007
16 when the patient was discharged from the
17 Vale of Leven Hospital."
18 A. That's correct.
19 Q. If we look at the reasoning for the prescription, you
20 have some discussion about that, particularly on
21 page 14. What did you understand the reason to be for
22 ciprofloxacin being prescribed to the patient at that
24 A. Well, it is difficult to be sure. Ciprofloxacin used to
25 be used for treatment of salmonella and, to some extent,
1 campylobacter, and used to be quite liberally prescribed
2 for that indication. I presume that they thought she
3 had a community-associated diarrhoea that might be one
4 of those agents. Although, subsequently, her laboratory
5 report was reported negative.
6 So I surmise that this was a hangover from previous
7 antibiotic advice that used to be issued that is not now
8 current and wasn't current at the time.
9 Q. Can I ask you this: was it appropriate to prescribe
10 ciprofloxacin at that time?
11 A. No, it was not.
12 Q. Should some antibiotic have been prescribed?
13 A. No, you would normally leave community-associated
14 diarrhoea, even if it is caused by salmonella, or
15 shigella, to recover on its own, although you might
16 consider, in an elderly and infirm patient, antibiotic
18 Q. The other point in particular I want to raise with you
19 in connection with this case is the treatment for
20 C. diff once she was in the Vale of Leven, and I think
21 she was managed on oral metronidazole; is that right?
22 A. That is correct, but she had a complicating bacteraemia
23 of her Clostridium difficile, for which microbiological
24 advice was sought, with the organism enterococcus
25 faecium, and that was treated with other antibiotics as
1 well, as is necessary in a bacteraemia complicating
2 C. difficile, and was managed with skill, I would say.
3 Q. Finally, then, if we turn to your conclusion, what you
4 tell us is that it is likely that this patient acquired
5 primary C. difficile infection due to apparently
6 inappropriate use of ciprofloxacin for a presumptive
7 infectious diarrhoea on an admission in December 2007;
8 is that your view?
9 A. Yes, I think that is my view. I mean, it is conceivable
10 that she acquired her C. difficile infection in the home
11 because nursing homes can also be sources, of course, of
12 infection of C. difficile, but I think a priori my
13 assumption is she acquired it in the Vale of Leven.
14 Q. We can leave that report there and move on to the next
15 case, which is Agnes Campbell.
16 Your report here, Dr Warren, is at EXP00220001. Can
17 we note, while we have the front page on the screen,
18 that Mrs Campbell was born on 21 February 1922 and died
19 on 13 January 2008?
20 A. That's correct.
21 Q. If we look at the death certificate at SPF00070001. Can
22 we see that Mrs Campbell was 85 when she died on
23 13 January 2008 and that she died in the
24 Vale of Leven Hospital? Can we also observe that
25 C. diff does appear in section 1 of the death
2 A. Yes.
3 Q. Looking at the medical history, if we turn to page 4 of
4 your report, Dr Warren, have you noted here that
5 Mrs Campbell was first of all admitted to the
6 Vale of Leven on 18 December 2007?
7 A. Yes, that's correct.
8 Q. What was the reason behind the admission then?
9 A. She was admitted with chest pain and an altered heart
10 rhythm called atrial flutter.
11 Q. She didn't spend much time there, because I think she
12 was, the following day, transferred to the
13 Royal Alexandra Hospital?
14 A. That's right, and she was diagnosed there as having had
15 a myocardial infarction.
16 Q. Following some treatment there, which I think also --
17 which I think included antibiotic treatment -- is that
19 A. It did indeed.
20 Q. She was transferred back, I think you tell us on page 5
21 of your report, to the Vale of Leven on
22 28 December 2007?
23 A. That's correct.
24 Q. She'd spent approximately nine days in the
25 Royal Alexandra Hospital. I think, if we move ahead
1 quickly -- we have already seen, in fact, she died after
2 six weeks in the Vale of Leven, on 13 January 2008?
3 A. That's correct.
4 Q. In that period, did she test positive for C. diff?
5 A. Yes, she did. She tested positive, I think, on
6 6 January.
7 Q. This is something you, I think, look at on page 6 of
8 your report, and perhaps it might be helpful if I put
9 the report from the lab on the screen; it is at
11 A. That is correct.
12 Q. We see the sample is collected on 6 January and received
13 on the 6th, and it is a positive result?
14 A. Yes.
15 Q. Can I then take you to that section of your report where
16 you review the antibiotic treatment? Your review begins
17 on page 13 of your report. Again, as you do in other
18 reports, you set out some of the guidelines. If we turn
19 to page 14, in the first main paragraph you say:
20 "This patient's provocative antibiotics were started
21 on the day of admission to the Vale of Leven and
22 continued from the next day whilst she was an inpatient
23 at the Royal Alexandra Hospital ..."
24 Did she also have antibiotics subsequently when she
25 came back to the Vale of Leven?
1 A. Yes, I think that is the case.
2 Q. If we then look at what she was prescribed before her
3 transfer to the Royal Alexandra, I think you have some
4 discussion about that on page 14; is that right?
5 A. Yes, there was an original suggestion that she should be
6 given Augmentin, but that doesn't seem to have been
7 administered. In fact, she was given intravenous
8 ceftriaxone, a third generation cephalosporin, and oral
10 Q. Just focusing on the ceftriaxone, if you turn to page 15
11 of your report, you make some observations in relation
12 to the ceftriaxone at this section. What is the point
13 you are making here?
14 A. The point I am making here is that ceftriaxone is
15 a third-generation cephalosporin, very wide-spectrum
16 agent, it has a high association with C. difficile, it
17 was regarded as the drug of choice at that time, the
18 cephalosporin of choice at that time, but it is an
19 antibiotic that has a high biliary excretion and, very
20 early on in the descriptions of use of ceftriaxone, it
21 was associated with C. difficile and I would not have
22 regarded it as an antibiotic that I would use outside
23 the area of meningitis or brain abscess, at that time.
24 Q. Why was it prescribed here?
25 A. It was prescribed as it was thought that she had
1 a pneumonia. I think that is the reason.
2 Q. Was it an antibiotic that would have been justified for
3 that on the guidelines?
4 A. Well, it depends whether you assume that she had severe
5 pneumonia, but I think there was evidence in this case
6 that her chest X-ray was clear on admission to hospital.
7 So that is not compatible with a diagnosis of severe
9 Q. Do you consider, then -- was this an appropriate
11 A. No, I don't think it was.
12 MR KINROY: My Lord, I wonder if we might clarify, Dr Warren
13 says it was regarded as the cephalosporin of choice at
14 that time, but he would have not used it himself. He
15 now says it was an inappropriate prescription. But does
16 he criticise the doctor for making the prescription
17 without hearing the reason for that?
18 A. I'm sorry, my Lord, I'm not sure I quite heard that.
19 LORD MACLEAN: You said it was the cephalosporin --
20 third-generation cephalosporin of choice.
21 A. Well, it was regarded as the parenteral cephalosporin of
22 choice. It would be unusual to regard
23 a third-generation cephalosporin as the parenteral
24 cephalosporin of choice. Most people in England and
25 Wales were using a second generation. That may not be
1 material. But the reason it was inappropriate was not
2 just that: the reason it was inappropriate was that the
3 lady did not have severe pneumonia, which is what the
4 guidelines said.
5 MR MACAULAY: Can I just see if I understand this? It may
6 have been the cephalosporin of choice for the
7 appropriate infection?
8 A. It might have been, although I would not have used
9 a third-generation cephalosporin in that way, but I am
10 not sure that there is much difference in terms of
11 selective ability for C. difficile between second- and
12 third-generation cephalosporins.
13 Q. If we move on to page 16, just below halfway you make
14 reference to clarithromycin. Was that prescribed in the
15 Vale of Leven on readmission?
16 A. On readmission, I think it was continued, yes. I think
17 it had been -- the oral clarithromycin had been started
18 on 18 December.
19 Q. In the Vale of Leven?
20 A. Yes.
21 Q. Was it continued in the Royal Alexandra Hospital?
22 A. Yes, it was, and given, I think, until 20 December, if
23 that tallies.
24 Q. As far as that was concerned, why was that prescribed
25 initially in the Vale?
1 A. Again, it was on the suggestion that this was a severe
2 pneumonia, and in a severe pneumonia it is reasonable to
3 cover unusual causes of pneumonia, such as legionella
4 and mycoplasma, as well as the more conventional
5 bacteria, or that is the received wisdom. Actually,
6 they are quite rare.
7 Q. Do you consider that this antibiotic should have been
9 A. No, because she didn't have severe pneumonia.
10 MR KINROY: My Lord, I wonder if we could also clarify that?
11 Is that because there is no record of it in the notes or
12 is it for some more definitive reason that the witness
13 can say there was no severe pneumonia?
14 LORD MACLEAN: Because she had the chest X-ray.
15 A. The chest X-ray is reported as clear.
16 MR KINROY: Sorry, my Lord, I was asleep!
17 DAME ELISH: My Lord, on that point, not specifically in
18 relation to pneumonia, but to clarify the position, if
19 my learned friend would, could it be the case, not
20 regarding pneumonia, but in developing chest infections,
21 that the X-ray may, indeed, appear clear, when, in fact,
22 the physical examination by the doctor would diagnose
23 a developing chest infection, perhaps not pneumonia?
24 A. I think it is excessively unusual.
25 LORD MACLEAN: What is?
1 A. To have a diagnosis of developing pneumonia with
2 a clear -- severe pneumonia with a clear chest X-ray.
3 I can't recall such a case.
4 DAME ELISH: Sorry, my Lord, not in respect of pneumonia,
5 but more moderately in respect of a chest infection.
6 A. Well, a chest infection is subcategorised either as
7 chronic obstructive pulmonary disease in this situation
8 or pneumonia. I don't think there is evidence that she
9 had chronic obstructive pulmonary disease, not that
10 I can recall from the notes, and certainly the
11 antibiotic therapy for that would not include
12 a third-generation cephalosporin either.
13 MR MACAULAY: Were these the only antibiotics that she was
15 A. No, she subsequently, I think, received some --
16 Q. Amoxicillin?
17 A. -- amoxicillin as well.
18 Q. Was that in the Vale of Leven or was that subsequently
19 in the Royal Alexandra? If we turn to page 5 of your
20 report, you mention, four or five lines from the top,
21 the ceftriaxone, the clarithromycin, and that was then
22 oral clarithromycin, until 20 December, and then oral
23 amoxicillin, despite a reported penicillin allergy; is
24 that right?
25 A. That is true.
1 Q. So that is still within the Vale?
2 A. Yes.
3 Q. Why was the amoxicillin being prescribed; are you able
4 to tell us?
5 A. They'd obviously decided that they didn't need
6 a broad-spectrum -- quite such a broad-spectrum agent as
7 the cefotaxime, so it is a substitute for that. It is
8 a narrow-spectrum agent that falls within the terms of
9 the guidelines as a sole agent had she got pneumonia; or
10 had, indeed, she got chronic obstructive pulmonary
11 disease, it would have been an appropriate prescription
12 for an exacerbation of that.
13 Q. Did she have that?
14 A. I think I thought she did. I have got it noted that she
15 received that until 25 December.
16 Q. That would have been in the Royal Alexandra Hospital?
17 A. Yes, indeed. That is right, I think. She didn't
18 continue to receive that in the Vale of Leven.
19 I correct what I said earlier.
20 Q. Can we then look at your review of diagnosis and
21 treatment for C. difficile? You begin looking at that
22 on page 20 of your report. You begin by telling us that
23 this is clearly a hospital-acquired C. difficile
24 infection, with the provocative antibiotics given 12 to
25 19 days earlier. Are these the antibiotics you have
1 been telling us about?
2 A. Yes.
3 Q. Looking to the timings here, perhaps we can just remind
4 ourselves, she comes back to the Vale of Leven on
5 28 December and she tests positive from a sample
6 collected on 6 January --
7 A. Yes.
8 Q. -- having spent some nine days in the Royal Alexandra
10 A. Yes.
11 Q. Are you able to come to a view as to where she
12 contracted C. diff?
13 A. Well, I thought it was most likely she acquired it in
14 the RAH at the time that she was receiving her
15 parenteral antibiotics, and she was present in the RAH
16 for a longer period.
17 I could also not find any trace of cases of
18 C. difficile diagnosed on ward 4, which is where she had
19 gone to in the Vale of Leven. So I thought the most
20 probable source, therefore, was in the Royal Alexandra
22 Q. That is in the period, then, of nine days or so between
23 19 December and 28 December 2007?
24 A. That was my view.
25 Q. Your view there, I think, is it based on the fact that,
1 in the course of the -- well, first of all, if it were
2 to be the Vale of Leven, would it have to be before the
3 transfer to the Royal Alexandra Hospital or could it be
5 A. It could have been either, is the answer to that
6 question, but obviously proportional to the duration
7 that she spent in.
8 You will note that, when she was transferred from
9 RAH to the Vale of Leven on 28 December, a patient that
10 we have just discussed, Julia Monhan, was discharged
11 from that same ward on that same day. So it might just
12 have been that she acquired it at that time.
13 So it is difficult, as ever, with acquisition, to be
14 absolutely certain.
15 Q. The reason I raise that is because, if we look at page 5
16 of your report, looking to the time that Mrs Campbell
17 comes back to the Vale of Leven, as you tell us, on
18 28 December she's transferred to ward 6, so she's in
19 ward --
20 A. That's true.
21 Q. So she's in ward 6 --
22 A. You will note from page 21 of my report that
23 Julia Monhan was discharged from ward 6 on that very
25 Q. I think we know from other sources -- does it come to
1 this: that the issue may be decided upon whether or not
2 we can say, looking to the position in ward 6 at the
3 relevant time, what the position was in relation to
4 C. difficile?
5 A. Yes, I think that's right. But quite evidently, there
6 was a case of C. difficile on the ward at that time who
7 was actually just in the process of being discharged.
8 Whether this patient went into the same room or not,
9 I cannot say from the medical notes. There had been
10 three other patients with ward 6 in the period -- with
11 C. difficile in the period from 15 to 22 December, so it
12 is possible that it was on ward 6. Although that would
13 be slightly unusual, because the antibiotics --
14 provocative antibiotics were largely prescribed in RAH.
15 Q. Just on that, I think I had taken it from you that
16 ceftriaxone and also the clarithromycin were prescribed
17 in the Vale of Leven before the transfer to the --
18 A. I think that's right. But she was admitted on the 18th
19 and there were relatively few cases then. There were
20 cases, as I say, between the 18th and the 22nd.
21 Q. Looking to the treatment, then, for C. diff, once it was
22 diagnosed, and this is something I think you address, if
23 I can take you to the relevant point, on page 27,
24 perhaps. I think you tell us that the patient was
25 transferred on the night of 6 January to ward 3 for
1 single room isolation and started on metronidazole,
2 albeit at twice the normal recommended dose -- that is
3 a dose of 800mg orally. So that was the commencement of
5 A. That's right, having been previously diagnosed on
6 ward 6. Right at the outset, it has to be said, on the
7 6th, she'd got what is noted as extensive bruising of
8 her lower abdomen and generalised tenderness. That, in
9 itself, suggests that we are dealing with severe
10 C. difficile infection, and did at that time suggest
11 severity, because it suggests an impending toxic
13 Q. If we just look at the treatment itself, then, have you
14 any views to express on the antibiotics and the dosage
15 that was prescribed?
16 A. Well, I don't particularly have a worry about the 800mg
17 dose, but apparently the patient was not written up, as
18 far as I could see, thereafter, for regular
19 metronidazole, and no metronidazole was charted the
20 following day, for reasons that are unclear to me.
21 If the patient was unable to take the drug orally,
22 it should have been given intravenously, and the patient
23 very rapidly developed a further progression of her
24 abdominal condition and Dr Akhter correctly considered
25 that this was suggestive of the most severe form of
1 C. difficile, a toxic megacolon.
2 All this time, the patient had continued with a low
3 blood pressure, which itself was an indication for
4 intravenous rather than oral metronidazole. I don't
5 think this 24-hour delay in treatment, effective
6 treatment, of her colitis was helpful to her prognosis
7 and condition.
8 She was given, in the end, some intravenous
9 metronidazole, I think on 8 January. Dr De Villiers,
10 a consultant microbiologist, had been consulted and had
11 recommended oral vancomycin, because he was obviously
12 aware of the emerging information suggesting that oral
13 vancomycin was helpful in severe -- severe forms of
14 C. difficile colitis.
15 I don't think she ever got any oral vancomycin.
16 Whether that was because she couldn't take by mouth or
17 not, I don't know, but certainly the situation was not
18 escalated and, in fact, the vancomycin was stopped,
19 because although it was charted, it had not actually
20 been given.
21 Q. I think that is what you allude to on page 28 of your
22 report. It is the second paragraph?
23 A. Yes, indeed, it is not clear to me why she was not being
24 given vancomycin. She could have been given vancomycin
25 by nasogastric tube and it could have been given in
1 liquid formulation and it could have been given in high
2 dose, I think.
3 Q. Just to be clear, what treatment did Mrs Campbell
4 actually receive then from 6 January for her C. diff?
5 A. I think she basically received some intravenous
6 metronidazole, initially orally, and then, from the 8th,
7 she received some intravenous metronidazole.
8 There was certainly a discussion of her developing
9 megacolon with Dr De Villiers, and he recommended oral
10 vancomycin in addition to the intravenous metronidazole,
11 which I think is correct, and he gave advice to seek
12 surgical intervention, which, again, I think is correct
13 because, although the prognosis in an 85-year-old with
14 severe C. difficile is, at best, not good, their best
15 chance of survival might be an immediate excision of
16 the colon under surgical guidance.
17 It is a very difficult decision to take, but the
18 evidence suggests that that perhaps gives a 15 per cent,
19 or thereabouts, survival benefit, in the hands of an
20 experienced senior colorectal surgeon with all the
21 assistance he can get in terms of high-dependency unit
22 or other care.
23 Q. You do, I think, mention this on page 29 of this report.
24 You mention the discussion with Dr De Villiers, who is
25 one of the consultant microbiologists, and then, towards
1 the bottom, you say that, when you're looking at a toxic
2 megacolon, you need urgent action; is that right?
3 A. I think absolutely that is the case. You require it
4 then and there. Even as a house officer, I worked for
5 an experienced colorectal surgeon who did, while I was
6 there, multiple total colectomies. It is a matter of
7 clinical assessment by a senior surgeon as soon as
8 possible, resuscitation and action.
9 I have to say, in his view, and my view, physicians
10 often hesitate about this, understandably in somebody
11 who is of advanced years, but if you are going to act,
12 it is urgent.
13 Q. Do you take from the records, just reading this
14 paragraph, that Dr Akhter had planned to involve the
16 A. He died to contact the surgeons in the RAH. I'm not
17 entirely clear why it was the RAH and whether or not
18 there were appropriate surgeons in the
19 Vale of Leven Hospital. That is beyond my knowledge.
20 He delegated that contact to his junior staff.
21 I think there was a period of 36 hours during which she
22 went from having a very severe disease to a terminal
23 disease, where no contact was made with somebody that
24 I can recognise as a senior surgeon.
25 Into all of that comes a consultation with Mr Nair,
1 who -- I am not certain of his status. I couldn't find
2 him on the current staff of the Vale of Leven Hospital
3 when I looked in the medical directory. Whether he is
4 a consultant or a junior doctor, I don't know, but I get
5 the feeling that he didn't actually see the patient and,
6 if he was an experienced colorectal surgeon, I would
7 have expected him to have seen the patient and given
8 what would have been a very difficult opinion.
9 Q. I think we know that there were no colorectal surgeons
10 in the Vale of Leven, so any surgery would have to take
11 place elsewhere?
12 A. Yes, well, they certainly asked -- contacted a junior
13 surgeon at the RAH, who delegated the opinion back to
14 the Vale of Leven, which I find hard to understand.
15 Q. Can we then move on to your conclusion in this
16 particular case, Dr Warren, on page 33? You begin by
18 "This patient received the antibiotics that provoked
19 her C. difficile in the Royal Alexandra Hospital in
20 treatment of an unconfirmed pneumonia."
21 I think we have seen that the antibiotics that you
22 mentioned at least were started in the Vale of Leven
23 before any transfer to the Royal Alexandra Hospital?
24 A. That is true, but they were continued in the RAH.
25 Q. As you point out, she developed severe C. difficile
1 colitis, and you say it is possible this was acquired in
2 the Vale of Leven, but I think you also say it is
3 possible it was acquired in the Royal Alexandra
5 A. I think that is the case.
6 Q. But in relation to treatment for the C. diff, so far as
7 you could make out, she received one dose of
8 metronidazole, but no further antibiotic treatment
9 because she didn't receive the oral vancomycin that had
10 been recommended?
11 A. That's right. She did get some more metronidazole, but
12 it was frequently omitted. I did notice that on the
13 drug prescribing chart. She didn't get an effective
14 surgical referral.
15 Q. Overall, then, your position in relation to this
16 particular patient?
17 A. I think she had antibiotics that possibly she didn't
18 need, since we have no evidence that she had a severe
19 pneumonia. So she had provocative antibiotics that she
20 didn't need.
21 She received some advice from consultant -- or the
22 team received some advice from the consultant
23 microbiologist. The consultant physician made the
24 correct diagnosis of a disintegrating toxic megacolon,
25 but she then didn't get all the treatment that might
1 have been appropriate for her severe C. difficile.
2 Q. Thank you. The next patient I want to take you to,
3 Dr Warren, is Jeanie Dow. Your report here is at
4 EXP01950001. We have the front page of your report on
5 the screen, and can we note that Mrs Dow was born on
6 17 May 1930, and she died on 16 January 2008?
7 A. We can. She was aged 77 on admission.
8 Q. I think, if we look at the death certificate,
9 SPF00120001, can we see here that she was 77 when she
10 died on 16 January 2008 in the Vale of Leven Hospital,
11 and can we note that there are three references on her
12 death certificate, but that does not mention
13 Clostridium difficile?
14 A. That is the case.
15 Q. Now, then, if we turn to your report and look at page 4,
16 I think on 5 January you tell us she has a brief
17 admission to the Vale of Leven Hospital, but I think she
18 spends a day there and then is returned back to the
19 nursing home; is that right?
20 A. I think that's right. It was quite difficult to make
21 out the notes, but that is the conclusion that I derived
22 from them.
23 Q. What was the purpose behind that brief admission at that
25 A. Well, she was said to have had difficulty in breathing
1 and episodes of breath holding. She'd got a past
2 history of chronic obstructive pulmonary disease and
3 irritable bowel syndrome and dementia. I don't think
4 the chest X-ray showed any evidence of a focal lung
5 lesion, and the abdominal X-ray showed distal faecal
6 loading and her previous hip operation. I think they
7 thought there was no evidence of infection, and it was
8 satisfactory to return her to the nursing home from
9 which the earlier patient, Julia Monhan, had also been
10 a resident.
11 Q. If we then look at page 5 of the report, have you noted
12 that, come 12 January, she has been admitted to the
13 Vale of Leven Hospital?
14 A. She had, and she had very clear evidence of pneumonia,
15 complicating her COPD. She was breathing fast and
16 shallowly, which is at a respiratory rate of 34, using
17 her accessory muscles of respiration. The nursing home
18 staff had found her pale, cyanosed and short of breath.
19 She had a tachycardia and she was very unwell.
20 Q. Indeed, we saw she died shortly after this admission on
21 16 January?
22 A. I think that is the case. In fact, I think there is no
23 doubt that she died of her pneumonia at that time.
24 Q. There had been a sample taken from her that did test
25 positive for C. diff?
1 A. Yes, it is difficult to be sure exactly when that was
2 reported, but my conclusion was I thought it was
3 probably reported after she had died.
4 Q. If we look at the lab report, it is at GGC00160047, can
5 we see that the sample is collected on 15 January,
6 received by the lab on the 16th and, as you pointed out,
7 it is a positive result?
8 A. Yes, it is. The reporting -- she's actually reported as
9 dying at 1.30 on the 16th, so it was reported after she
11 Q. We do have an infection control card, SPF00510001. Can
12 we see there's an entry which reads:
13 "Informed by lab staff. Advised ward. Patient died
14 this am."
15 Although it is difficult to work out the date, the
16 date of death was the 16th --
17 A. It is not possible, is it, that the patient died on the
18 18th and on the 16th? She died on the 16th. I think
19 this is an inaccuracy on the card.
20 Q. If that is an "8"?
21 A. Well, I think it pretty clearly is, as far as I can see.
22 Q. You may be right. If we look at the nursing notes
23 themselves on GGC01600055. Certainly if we are looking
24 at the entry for the 16th or, indeed, for the 15th,
25 I don't think we see any reference there to the ward
1 being told that she was C. diff positive.
2 A. No, I don't think so. In fact, I felt very strongly in
3 this case that C. difficile played no part in this
4 lady's death. Whether it was an incidental finding or
5 a measure of cross-infection, I find difficult to
7 Q. Then, if we look just at your review of her antibiotic
8 treatment generally to see what relevance that may be,
9 on page 11 of your report, towards the bottom of that
10 page, I think what you tell us is that this patient only
11 appears to have received a single antibiotic course from
12 her hospital record, although, in the absence of a GP
13 referral letter or history from the nursing home, one
14 cannot be sure that she did not receive antibiotics
15 whilst in the nursing home that may be relevant.
16 A. I think that's correct. She received a course of two
17 antibiotics: intravenous co-amoxiclav and
18 clarithromycin. They were appropriate for severe
20 Q. These were antibiotics she received at the time of
21 the admission in the course of which she died?
22 A. That's true.
23 Q. You tell me: do these antibiotics play any part, then,
24 in her acquisition of the C. difficile?
25 A. It is possible. It is possible. But the interval is
1 very short. So I think it is difficult to be sure.
2 As I say, we don't know about whether she had had
3 any antibiotics while she was in the nursing home.
4 Q. In relation to treating for C. difficile, I think, as
5 you indicated, certainly the diagnosis didn't come
6 through until about the time of death. So there was no
7 treatment of that?
8 A. There was no treatment. From the notes, I couldn't
9 derive why they had sent a faeces sample. There is not
10 any obvious diarrhoea -- I presume there was diarrhoea,
11 but there is no obvious account of it.
12 MR KINROY: My Lord, I wonder if I could clarify if this is
13 possibly a case of a patient who was a carrier of
14 C. diff and who developed loose stools for some reason
15 other than C. diff illness, and quite fortuitously then
16 the bacterium was discovered in the faecal sample?
17 A. Possibly. I think it is unusual to discover the toxin
18 in a carrier. It is more normal to discover the
19 organism. So whether she was, if you like, in an early
20 stage of incubation of C. difficile and, if she had
21 lived a bit longer, it would have been evident,
22 I think -- I prefer that alternative solution, rather
23 than she was colonised. But it was certainly incidental
24 to her illness at that time.
25 MR MACAULAY: We can move on from Mrs Dow to Mr Boyle, who
1 is the next case. Mr Boyle's report is at EXP01970001.
2 if we just look at the front page of your report,
3 Dr Warren, can we note that Mr Boyle was born on
4 8 January 1918 and he died on 6 February 2008?
5 A. That's right, and he was admitted initially to RAH on
6 3 January 2008, five days short of his 90th birthday.
7 Q. Then can we just look at his death certificate at
8 SPF00020001? I think, as you have pointed out, he was
9 90 when he died on 6 February 2008, and he died in the
10 Vale of Leven Hospital, and we do see that
11 Clostridium difficile enteritis does appear in the first
12 part of his death certificate.
13 A. That's correct.
14 Q. Then, if we move on to the body of your report and look
15 at page 4, as you mentioned a moment ago, you have noted
16 that he was admitted to the Royal Alexandra Hospital,
17 and that was on 3 January 2008? Is that right?
18 A. That's right. He had fallen in sheltered housing and
19 there was a query of whether he'd got a fracture of
20 the neck of his femur. That proved not to be the case
21 radiologically, and the next day he was transferred to
22 the Vale of Leven Hospital. Oh, no, not the next day,
23 sorry, he was transferred on a ward there and he was
24 noted to have speech problems. It was actually later,
25 on 10 January, he was transferred, I think, to the
1 Vale of Leven, if that is correct.
2 Q. That is what you note towards the bottom of page 4, he
3 was transferred to --
4 A. That's correct, sorry about that.
5 Q. I think, as we noted a moment ago, he died a few weeks
6 after that, on 6 February 2008?
7 A. That's correct.
8 Q. In relation to C. diff -- and I think you touch upon
9 this first of all towards the bottom of page 5 of your
10 report -- I think you noted that he did test positive
11 for C. diff in respect of a sample collected from him on
12 22 January 2008?
13 A. Yes, that is the case. For some reason, it looks as if
14 that was received in the laboratory with all the caveats
15 we have got about dates on 25 January.
16 Q. I will put the lab report on the screen for you. It is
17 at GGC00030025. Here we have the lab report. As you
18 noted in your own report, the collection date is
19 22 January, received on 25 January, what, three days
20 later, and we can note from this that it is a positive
22 A. That's correct.
23 Q. So far as the ward being aware, if we look at the
24 medical records at GGC00030042, can we note here that on
25 the 25th, at 1450, there is a note:
1 "Received notification that Jake is C. diff
3 A. That's correct.
4 Q. So that would coincide with the date of receipt --
5 A. That's right.
6 Q. -- in the lab? If we look at the infection control card
7 at SPF00410001, again, this looks like -- the date is
8 not absolutely clear. It looks like 25 January:
9 "Advised isolate and commence oral metronidazole."
10 A. Yes.
11 Q. So a sample is collected on the 25th and it would appear
12 the ward is aware of that situation on 25 January, which
13 you have noted, I think, to be a Friday.
14 A. I think that is right.
15 Q. If that is wrong, we will be told in early course?
16 MR PEOPLES: I think we can confirm from the expert on my
17 left that it was a Friday.
18 MR MACAULAY: Can I then take you to your review of his
19 antibiotic treatment? You begin that analysis on
20 page 8, and if we look to page 9 to see what antibiotics
21 were prescribed, you mention there that Mr Boyle was
22 prescribed amoxicillin, together with flucloxacillin,
23 from 14 January onwards; is that right?
24 A. That is correct. This was for suspected cellulitis
25 around a graze. I noticed, when I looked at the
1 records, that initially, on 7 January, it had been noted
2 that he'd got a graze on his left shin, and that was
3 treated with topical iodine.
4 Q. That was in the Royal Alexandra Hospital?
5 A. That was in the Royal Alexandra Hospital. By
6 12 January, this was noted to be swollen as well, and
7 the diagnosis of cellulitis was reached, rightly or
8 wrongly -- it is difficult to assess, but swelling and
9 perhaps redness would be an indication of that -- and it
10 was for that that he was prescribed his antibiotics.
11 Q. Were they appropriate, in the circumstances?
12 A. I don't think the use of amoxicillin was appropriate at
13 all, since that is not active against Staph aureus,
14 which is the commonest cause of such infections. The
15 British National Formulary would regard flucloxacillin
16 with penicillin as appropriate, benzyl penicillin or
17 penicillin V. I think that the penicillin V or the
18 benzyl pen is superfluous and flucloxacillin alone is
19 perfectly adequate for the treatment of staphylococcal
21 DAME ELISH: My Lord, in relation to this particular point,
22 I wonder if my friend could refer to the clinical record
23 and is it possible, in fact, that he was prescribed the
24 amoxicillin for a potential chest infection, rather than
25 for the cellulitis.
1 LORD MACLEAN: Is this the Royal Alexandra?
2 DAME ELISH: No, the Vale of Leven.
3 MR MACAULAY: I can certainly take you to the clinical
4 notes. If we turn to page 15 of the records, I think
5 the entry you have in mind is the one on 14 January --
6 A. It is, indeed.
7 Q. -- in the sort of thicker black pen. I think we
8 understand that to be Dr Herd, but I may be wrong about
9 that. There is reference to:
10 "Cellulitis of left leg. Also chesty, but refuses
11 to begin [something or other]."
12 Can you read that for us?
13 A. Yes, I can now decipher the word "chesty" which had
14 eluded me earlier, which I would suggest is not
15 a diagnosis, to be "chesty". You know, you either need
16 to decide he's got pneumonia or chronic obstructive
17 pulmonary disease or he's got some evidence of a chest
19 DAME ELISH: I understand, my Lord, if it assists the
20 doctor, that the clerking record may also indicate that
21 there were scattered crepitations noted by the --
22 A. Crepitations are common. They do not necessarily equal
23 pneumonia or infection.
24 MR MACAULAY: What would you want to see if the doctor was
25 proceeding on the basis of there being an appropriate
1 diagnosis of a chest infection so as to justify the
3 A. Well, I hate the term "chest infection", although I use
4 it myself because it is in common parlance. I think
5 I would want a history of chronic obstructive pulmonary
6 disease and evidence of purulent sputum as one
7 indication for giving amoxicillin or evidence of --
8 radiological evidence of pneumonia as an alternative,
9 I think, particularly in hospital, and particularly when
10 you are having due regard to the need to be careful
11 about antibiotics because you have C. difficile present.
12 I think it is fair to say that, if you have
13 C. difficile present in the environment, the risk of
14 acquiring it is enhanced and it behoves everybody to be
15 extra careful about giving antibiotics and the evidence
16 for giving them before doing so.
17 Q. My learned friend has raised a couple of points there.
18 Do they in any way dissuade you from your view that the
19 amoxicillin was inappropriate in this case?
20 A. I think it is questionable whether the amoxicillin was
21 appropriate. I won't perhaps go as far as I did go and
22 say it was totally inappropriate, but I really think the
23 evidence is very poor to justify its use.
24 Q. I think Mr Boyle was somebody who did have a problem
25 with his swallow; is that right?
1 A. I don't recall that, but you may be able to direct me in
2 the appropriate direction.
3 Q. I think, if we go back to the clinical notes at page 16,
4 the entry on the 16th suggests he's been reviewed by
5 the -- is that the speech and language therapist, who
6 feels that he should be nil by mouth? Do you see that?
7 A. Yes, I do see that. So there is a question about the
8 integrity of his airway and whether or not he would have
9 a particular susceptibility to a chest infection.
10 Q. So someone who presents with this problem could be
11 susceptible to --
12 A. I think if you have difficulty in your swallowing
13 reflex, you are more susceptible to a chest infection by
14 aspiration. That in itself doesn't justify treating it.
15 DAME ELISH: My Lord, I have just had my attention drawn to
16 one document, which is the clerking-in, which refers to
17 "?aspiration pneumonia".
18 A. Where is the evidence of a pneumonia?
19 DAME ELISH: That is simply what is recorded there at that
21 A. Quite so.
22 DAME ELISH: There are the scattered crepitations, but there
23 is also "?aspiration pneumonia".
24 A. I accept the observation, but the question of aspiration
25 demands, then, a chest X-ray, if you think he has got an
1 aspiration pneumonia.
2 MR MACAULAY: I'm sorry?
3 A. If you think a patient has an aspiration pneumonia, you
4 need to do a chest X-ray to verify that they have got
5 a pneumonia.
6 LORD MACLEAN: And there wasn't one here?
7 A. There wasn't one as far as I can see.
8 MR MACAULAY: There were some blood samples taken, I think,
9 if we look at page 20 of the records. The specimen was
10 taken on 15 January. Do we look for evidence of
11 infection here? You can help me with this.
12 A. Well, there is a mildly raised C-reactive protein, but
13 that could be consistent with infection around his
14 graze, just as much as it could be with anything going
15 on in his chest. I think there is some evidence of --
16 let's just have a look. No, it is not on that report.
17 There is some evidence of mild renal impairment,
18 perhaps, or dehydration with a raised creatinine of 134,
19 but it is not exceptionally raised.
20 Q. Page 22, to see what his white cell count is like, if we
21 look at that.
22 A. His white cell count is slightly raised, but
23 unremarkable. Again, consistent with what is going on
24 in his shin, just as much as what might be going on in
25 his chest.
1 Q. So, then, looking at the points that have been raised
2 and the results I have taken you to, then, Dr Warren,
3 what is your final position in relation to the
4 amoxicillin as to its appropriateness or otherwise in
5 the circumstances?
6 A. Well, I am unconvinced that the case has been made that
7 he required amoxicillin for an aspiration pneumonia or
8 "chesty". It is possible that he had that, but I would
9 say the evidence to substantiate that is really limited
10 to a few creps at his base, which is neither here nor
12 Q. Then if we turn to look at your review for his C. diff
13 infection, you begin looking at that on page 11 of your
14 report and, if we turn to page 13, you give some views
15 there as to where you consider the infection was
16 acquired. You say that the infection was probably
18 A. Well, it is not entirely clear to me where he developed
19 his diarrhoea, or whether he had diarrhoea on transfer
20 to the Vale of Leven or not.
21 Q. So it wasn't clear from the records?
22 A. It wasn't clear from the records, as far as I could see.
23 Q. But we do know, I think, from what we have, that he was
24 transferred to the Vale of Leven on 10 January --
25 A. Yes.
1 Q. -- and the positive specimen was collected from him some
2 12 days later, on 22 January?
3 A. That's right, and he had had antibiotics in the
4 Vale of Leven, so I think it is more likely than not
5 this was acquired in the Vale of Leven.
6 Q. What about the treatment, then, for C. diff?
7 A. Well, as far as I can see, notification was at 1450 on
8 the Friday. The infection control was notified, the
9 doctor was notified, the family was notified, he was
10 transferred to a side room and he was started, I think,
11 on metronidazole on that day of diagnosis.
12 Q. We'll just get the page up on the screen. It is
13 page 15.
14 A. That's right.
15 Q. You say he was started on the metronidazole on the 25th?
16 A. I think that's right.
17 Q. That ties in with when the diagnosis was made, but of
18 course, the specimen was collected on the 22nd?
19 A. I think that's correct.
20 Q. Do you see a delay there between --
21 A. Yes, I do see a delay there, and I also note that this
22 result was not authorised by a consultant
23 microbiologist. I am not even sure a consultant
24 microbiologist was aware of this diagnosis. Therefore,
25 although I don't know, in any of the cases that I have
1 reviewed, whether a consultant microbiologist was
2 responsible for phoning the report, or whether this was
3 left to technical staff, there doesn't seem to have been
4 a consultation about this chap's treatment at that time.
5 Q. Again, you do look at this, to some extent, in your
6 overview as well, but if we put the report back on the
7 screen to understand the point you are making, this is
8 at GGC00030025?
9 A. Yes, you can see that the terminology used is, in the
10 bottom left-hand corner, "Technically validated by
11 N Coll". I don't know whether N Coll is a real name or
12 not, but "technically validated" indicates to me this
13 report was issued by a medical laboratory scientific
14 officer rather than authorised by a consultant medical
16 Q. I think you do see in other cases that reports are
17 authorised by a microbiologist.
18 A. In almost all cases, except one, which was actually
19 reported on the same day and was, again, authorised by
20 N Coll. That was the case.
21 Q. What are you saying, that you don't know from
22 information you have seen whether or not
23 a microbiologist was aware that Mr Boyle had tested
25 A. That is the case and, in fact, I can't even put it --
1 I can't even put it that a consultant microbiologist who
2 would normally be aware was aware in this case at all,
3 and that is unusual.
4 Q. You would expect, would you, a microbiologist to be
5 aware of a positive result for C. difficile?
6 A. Yes, I would. It is notable that there is no
7 requirement -- and we may be going to deal with this
8 elsewhere -- for notification of a consultant
9 microbiologist on the tests and the laboratory
10 procedures for conducting C. difficile tests at this
11 time, and I consider there should have been, and
12 I consider this was then an important enough diagnosis
13 to bring immediately to the attention of consultant
14 microbiologists, so that they could issue the report
15 themselves and consult over it, and, indeed, this would
16 be the case if testing was done out of hours. This is
17 a high mortality condition of great importance.
18 Q. Then, if we turn finally to your conclusion, the points
19 have, I think, in the main been covered.
20 Looking at the third paragraph, you again mention
21 the three-day delay, which you say is undesirable.
22 I suppose the other side of that is that, if there is
23 a delay in diagnosis and treatment, then, if you are on
24 antibiotics which are provocative, the provocative
25 antibiotics continue during that period?
1 A. That is the case, and that was the case here.
2 Q. Insofar as the metronidazole treatment was concerned,
3 was that the appropriate course of action?
4 A. It is difficult to be sure, but I think so at that time.
5 My difficulty in saying it was appropriate is that
6 I couldn't find any trace of any information that
7 permitted me, even in retrospect, to assess severity.
8 There was no abnormal X-ray, there was no white count,
9 there was no creatinine, all of those things that
10 I would require to estimate the severity.
11 Of course, also material is the question of whether
12 or not the patient could or would take oral
13 metronidazole or whether other opportunities to give him
14 therapy for his C. difficile should have been
15 considered. So if he was unable to take oral drugs,
16 I would have certainly given him metronidazole
17 intravenously, and I would have considered my ability to
18 deliver, perhaps, vancomycin, if not metronidazole, by
19 a nasogastric tube, or even, in extremis, I have used it
20 rectally, or advised it is used rectally.
21 Q. Did you see if a microbiologist was involved at all with
22 this patient?
23 A. I couldn't see any evidence that a microbiologist was
24 involved in this case.
25 Q. Do you think that, standing the fact that he contracted
1 C. diff, it would appear from the specimen that was
2 collected on 22 January and, indeed, looking to the
3 death certificate, C. diff does feature in part I of
4 the death certificate on 6 February, some time
5 afterwards, whether a microbiologist should have been
6 involved to review the position?
7 A. It was my view that certainly when he wasn't much
8 better, certainly on the Sunday, the 3rd, it would have
9 been appropriate to have talked to a microbiologist
10 about the difficulty of treating the C. difficile
12 DAME ELISH: My Lord, I wonder if my learned friend could
13 clarify with Dr Warren whether or not, in an
14 89-year-old, might nasogastric treatment or rectal
15 administration be considered a fairly aggressive
16 treatment which the clinician might decide was not
18 A. Yes, I accept that they are aggressive treatment. But
19 nasogastric treatment is not particularly aggressive.
20 It is quite commonplace to have -- pass a nasogastric
21 tube. The patient may not tolerate it, but you can but
22 give him or her the opportunity.
23 I think this is an aggressive condition, as the
24 Inquiry has realised, and doing the most you can for the
25 patients is certainly justified.
1 LORD MACLEAN: He could have received it intravenously,
2 couldn't he, either metronidazole or vancomycin?
3 A. As always, there is a question of consent, if you are
4 giving a drug intravenously or you are giving a drug by
5 something like a nasogastric tube that you have to put
6 in, but, yes, I think he could have received intravenous
8 MR MACAULAY: My own impression is intravenous metronidazole
9 can work, but intravenous vancomycin not so?
10 A. That is the case. I think if you think somebody is
11 going to die of C. difficile in short order, both are
12 justified, both oral vancomycin or vancomycin by
13 nasogastric tube and intravenous metronidazole. I think
14 both are justified as treatment that can be offered.
15 Q. I think the next case on my list was Mrs McGinty, but
16 I think I have been asked to hold fire on that one until
18 So if you are prepared to jump on to the next case,
19 perhaps out of your order, Dr Warren, and that is
20 Jessie Jones.
21 A. Okay.
22 Q. Your report here we can find at EXP01960001. We see
23 from the front page of your report that Mrs Jones's date
24 of birth you have noted to be 31 July 1923?
25 A. That's right. She was aged 84 at her admission on
1 2 February with a right-sided weakness.
2 Q. Mrs Jones was a patient who was admitted but was
3 subsequently discharged home?
4 A. I think, on 2 February, she was transferred, as far as
5 I can make out, to the specialist stroke unit at the
6 Western General Hospital. So I don't think she went
7 home. I think her stroke required specialist care.
8 Q. If we then turn to page 5 of your report, where I think
9 you give us some insight into her medical history,
10 I think you mention, first of all, that, on
11 14 November 2007, she had a day admission to the
12 Vale of Leven; is that correct?
13 A. Yes, I think she'd had difficulty with swallowing, which
14 is what "dysphagia" means, and she was taking a proton
15 pump inhibitor at that time, which some people consider
16 predisposes to C. difficile. I'm not an expert in that
18 Q. But you also tell us that, on 2 February 2008, she was
19 initially in the Vale of Leven, but then she was
20 transferred to the Western Infirmary?
21 A. That's right.
22 Q. What was that for?
23 A. That was for the right-sided weakness she presented with
24 that was thought to be a stroke.
25 Q. Was she then subsequently, if we turn to page 6 of your
1 report, readmitted to ward F of the Vale of Leven
3 A. That's right, on 8 February.
4 Q. What was the reason for that, then, at this time?
5 A. I think that was for rehabilitation after her stroke, in
6 the first place.
7 Q. She, I think, then -- I think you tell us this on page 7
8 of your report -- tested positive for C. diff following
9 taking a sample on 16 February?
10 A. That's correct. There had been some question about
11 whether something else has going on. I think the record
12 on the top of page 6 on 8 February suggests that they
13 were worried about either a renal stone or gallstones,
14 and they carried out appropriate investigations for that
15 and, indeed, they prescribed an antibiotic for that.
16 Q. We will return to that.
17 A. Fine.
18 Q. Can I then look at the lab result, at GGC21010087?
19 So we note here that the sample was collected on
20 16 February, and you have told us in your report that
21 that was a Saturday --
22 A. Yes.
23 Q. -- early morning. Received by the lab on the 18th,
24 which would be the Monday, and it is a positive result?
25 A. That's true.
1 Q. If we look at the nursing notes at page 119, we see the
2 entry for the 18th beginning to the left of the page,
3 18/2, about six lines from the top. If we move across
4 the page, three or four lines before halfway, before we
5 see the date for the 19th, can we see the entry:
6 "C. diff as advised by infection control."
7 A. Yes.
8 Q. It would appear the lab knew, then, as at the same date
9 as the receipt of the sample in the lab?
10 A. That's correct.
11 MR MACAULAY: This might be an appropriate time to have
12 a break.
13 (3.05 pm)
14 (A short break)
15 (3.25 pm)
16 MR MACAULAY: We are looking at the Jessie Jones case. Can
17 I look at your review of her antibiotic treatment? You
18 begin that on page 13. If we turn to page 14 and focus
19 on the antibiotics that Mrs Jones was prescribed in the
20 Vale of Leven, you mention there three antibiotics:
21 ciprofloxacin, ceftriaxone and clarithromycin. Let's
22 look at the ciprofloxacin, first of all.
23 Were you able to ascertain why that was prescribed?
24 A. Yes. I think it was thought that she might have a renal
25 stone, from the description of her abdominal pain and
1 the fact that a renal ultrasound was done. Urinary
2 infection on top of renal stone is quite common. Her
3 urine was actually sent and proved to be sterile, and
4 the renal ultrasound was negative. So she didn't have
5 a renal stone. But that was why the ciprofloxacin
6 I think was chosen. It was chosen in accordance with
7 guidelines because they thought she had pyelonephritis
8 complicating a renal stone.
9 Q. Just looking at that thought, would that be an
10 appropriate reason for starting on ciprofloxacin?
11 A. Yes, it would have been.
12 Q. But, then, once it became clear that the urine sample
13 was sterile and she didn't have a renal stone, what
15 A. Well, the antibiotic should have been stopped, but it
16 was continued.
17 Q. I think you tell us that the ciprofloxacin was
18 prescribed from 8 to 16 February. That is eight days or
19 so. When do you suggest they should have been aware
20 that it wasn't necessary?
21 A. Well, as soon as they had got both the negative urine
22 and the negative ultrasound back.
23 Q. Have you given us a date for that?
24 A. I don't know whether I have, but I can find one. The
25 urine was taken on 9 February, and it was on that date
1 that the renal ultrasound was carried out.
2 The urine was actually reported on 11 February. So
3 certainly by 11 February both should have been stopped.
4 The ciprofloxacin should have been stopped, in my view.
5 Q. Then the next antibiotic you mention there is the
6 ceftriaxone. You discuss that on page 16 of your
7 report, the first paragraph below halfway. Why was that
9 A. Let's just look at that. I think that was given because
10 she had, by then, got a small opacity in her lung, in
11 the right costophrenic angle, and she'd got a high white
12 count. They weren't quite sure what was going on, so
13 they prescribed the ceftriaxone and the gentamicin,
14 presumably on the assumption that she'd got an ongoing
15 severe infection and they weren't quite clear whether it
16 was chest or, again, urine.
17 Q. Was that an appropriate prescription?
18 A. Again, I don't think she had evidence of a severe
19 community-acquired pneumonia. She had a small lung
20 shadow. It is difficult to be sure. Having said that,
21 she'd got -- I wouldn't have used, as I say,
22 a cephalosporin in that situation anyway, because much
23 of its spectrum is covered by the gentamicin. I might
24 have used something simpler, like penicillin and
25 gentamicin. In the context of the guidelines of severe
1 systemic infection, it might be difficult to criticise.
2 Q. I suppose, in any event, it would have been totally
3 irrelevant. If that was prescribed on the 16th and
4 17th, by then, the sample that proved to be positive had
5 been taken?
6 A. Yes, and, indeed, she only had two doses of ceftriaxone.
7 So although C. difficile after two doses of ceftriaxone
8 is recorded, it is one of the reasons I am cautious
9 about the agent. I think we have to assume it was
10 probably the ciprofloxacin that was the significant
11 provocative factor.
12 Q. This wouldn't be implicated in the causation. Might it
13 be implicated in whether or not the disease was --
14 A. Progressing, yes, I think that is fair.
15 Q. -- progressing? What about, then, the clarithromycin?
16 Is that really beyond the time period we are looking at?
17 A. Yes, that is the case. By that stage, she was being
18 readied for discharge home. The patient was thought to
19 be penicillin allergic, so it was inappropriate to give
20 her plain, simple benzyl penicillin, and they gave her
21 erythromycin. There was, in fact, a sputum cultured
22 appropriately, which did show that she had
23 a pneumococcal infection.
24 Six antibiotic susceptibilities were reported with
25 that, which I think offers plenty of choice for
1 a clinician to use the wrong agent.
2 Q. Let's move on from that to your review of the diagnosis
3 and treatment for C. difficile. If we turn to page 25.
4 A. There was some delay, again, in the transit of her
5 faecal sample, from the time it was collected on the
6 ward to the time it was tested. I thought there was
7 two-day delay there. But once it arrived in the lab, it
8 was tested promptly. I think she developed symptoms
9 suggestive of her C. difficile on 15 February. Although
10 she had had some vomiting and diarrhoea earlier, I think
11 the vomiting was almost certainly unrelated to
12 C. difficile. It is very seldom a feature of that
14 Q. Was it metronidazole that she was started on?
15 A. Yes, she was given metronidazole by mouth and the other
16 antibiotics were stopped. In this case, she had a very
17 high white count. I think we can note that it was over
18 27,000 x 10 to the 6th per litre. That, in retrospect,
19 would indicate severe C. difficile, but at the time,
20 I think there were no good laboratory parameters for
21 severe C. difficile.
22 Q. So the metronidazole was an appropriate response?
23 A. Acceptable at the time.
24 Q. Then, if we look at your conclusion, Dr Warren, on
25 page 26, you begin by telling us, and I think you have
1 already touched upon this, that you consider that it was
2 the ciprofloxacin that was the provocative agent here;
3 is that right?
4 A. That is correct.
5 Q. In relation to the acquisition of the infection, I think
6 your thinking was that the infection was acquired in
7 ward F?
8 A. That's the case, yes, at around the time the
9 ciprofloxacin was prescribed. She made a good recovery
10 on the oral metronidazole. Boldly, she was subsequently
11 treated with clarithromycin, which might have provoked
12 a relapse. But I see no evidence that it did so.
13 Q. The next case, then, that I would like to take you to is
14 that of Anne Gray.
15 We have your report for this patient at EXP01900001.
16 I think we can see from the front page of your report
17 that Dr Gray was born on 26 November 1922 and died on
18 2 March 2008?
19 A. That's correct. She was aged 85 at the time of her
20 admission, on 20 January, to RAH with a fractured neck
21 of femur.
22 Q. If we look at the death certificate, first of all, at
23 SPF00170001, as you have pointed out, she was 85 at this
24 time when she died, on 2 March 2008; she was in the
25 Vale of Leven when she died; and can we note that
1 Clostridium difficile infection was in part I of
2 the death certificate?
3 A. Yes, indeed.
4 Q. As you mentioned a moment ago, and turning to page 4 of
5 your report, she was admitted, first of all, to the
6 Royal Alexandra Hospital on 20 January 2008; is that
8 A. That's correct.
9 Q. She clearly had a fall, I think, and fractured the neck
10 of her femur?
11 A. I think that is correct. She had the femur replaced
12 with an Austin Moore prosthesis. It is noteworthy that
13 she had an exacerbation of chronic obstructive pulmonary
14 disease at the time and, in fact, that slightly delayed
15 her operation. She was also catheterised, as is normal,
16 if you are doing a hip replacement.
17 Q. She did receive some antibiotics at this time when she
18 was in the Royal Alexandra Hospital?
19 A. She did. She received ceftriaxone for her chest, which
20 is a suitable treatment for severe COPD, and I guess
21 they were in a hurry to get a response, and for some
22 reason they didn't realise that that adequately covered
23 her surgery, and they gave her cefuroxime prophylaxis to
24 cover her surgery as well.
25 Q. Be that as it may, is she transferred to ward 14 of
1 the Vale of Leven on 4 February 2008?
2 A. Correct.
3 Q. I think, as we noted a moment ago, a month or so later,
4 on 2 March, she dies in the Vale of Leven?
5 A. That's right.
6 Q. Then in the interim, I think, as you point out on
7 page 5, first of all, there was a negative result for
8 C. diff in relation to a sample collected I think on
9 6 February; is that right?
10 A. That's correct. She complained of vomiting and
11 diarrhoea. As I have said, vomiting is an unusual
12 feature of C. diff and the C. diff test was negative,
13 a viral PCR for norovirus, which is a common cause of
14 hospital problems, causing mainly vomiting and some
15 diarrhoea is possible.
16 Q. But then, some time after that, I think in relation to
17 a sample collected on 26 February, they did get
18 a positive result, and this is something you discuss
19 towards the top of page 6 of your report?
20 A. That is true. The evaluation notes are fairly full as
21 to what infection precautions they actually took,
22 unusually the case, signs and trolley, et cetera. They
23 spoke with an unnamed microbiologist and the junior
24 doctor spoke to the SHO and she was started on
25 metronidazole, if she was able to tolerate that, on the
1 26th, when the report was issued.
2 Q. I will just come back to that particular point in
3 a moment. Let's look at the lab result first of all;
4 it is at GGC00240026.
5 A. It was a positive report.
6 Q. As you have indicated in your report, the sample is
7 collected on the 26th, received on 26 February and it is
8 a positive result?
9 A. Yes.
10 Q. Just picking up the point you make about the
11 metronidazole, if we look at the drug Kardex, which we
12 will find at page 71 of the records, we see here the
13 metronidazole seems to have been prescribed on the 27th,
14 which is, I think, a day later than you thought?
15 A. Yes, I think that is true.
16 Q. Can we also see that that was three times a day, and the
17 first administration is actually on the 28th?
18 A. I think that is correct.
19 Q. Judging by what is in the document?
20 A. I think that is correct. So there may have been some
21 delay in initiating the metronidazole, because it was
22 certainly discussed, as I have indicated, on the 26th.
23 Q. I think that is fair. I think, if you look at the
24 infection control card, at SPF00550001, there are two
25 entries that might be of interest. There is one on the
2 "Contacted by ward sister. Patient symptomatic but
3 had negative specimen. Nursed in isolation as patient
4 very unwell."
5 Do you see that?
6 A. I do, indeed. I looked very hard to try and find that
7 earlier report, and I, in fact, went far back before
8 I could find anything. At the time of her norovirus
9 infection, I assume that was what they were referring to
10 as negative.
11 Q. I think the only one we have is the one of 6 February
12 that we looked at?
13 A. February.
14 Q. Then we see the entry for 26 February:
15 "Informed by lab staff positive result. Spoke with
16 SHO and consultant microbiologist and advised
17 metronidazole suspension if patient can tolerate."
18 A. Yes.
19 Q. It seems, although that was the advice on the 26th, on
20 the face of it, looking to the Kardex, it didn't
21 actually take place until the 28th.
22 If we then look at your review of her antibiotic
23 treatment, you start doing that on page 10. Am I right
24 in thinking -- you can correct me if I am wrong -- that
25 in her time in the Vale of Leven Hospital, and that is
1 from 4 February, Dr Gray did not receive any
3 A. That is my understanding. So if this was Vale of Leven
4 acquired, it is slightly unusual, because normally, as
5 I have indicated in my other reports, the antibiotics
6 and the acquisition seem to chime in terms of days, but
7 it is entirely possible that you change the faecal flora
8 and two or three days later you acquire C. difficile.
9 Q. If we turn to page 11 of the report, I think, in fact,
10 you do tell us there that there were no antibiotics in
11 the Vale of Leven, but you do mention the, as it were,
12 I will perhaps refer to it, the double dose of
13 ceftriaxone that she received in the Royal Alexandra
15 A. She received more than a double dose. She received six
16 days of ceftriaxone --
17 Q. Yes.
18 A. -- and a single dose of cefuroxime.
19 Q. Are these of the provocative type?
20 A. Yes, they are.
21 Q. So without going into the detail of that, would this be
22 the culprit antibiotic that would make her susceptible
23 to C. diff?
24 A. Yes.
25 Q. Then, if we turn to page 14, you begin there your review
1 of her diagnosis for C. diff. I think we have already
2 looked at the position with regard to metronidazole.
3 Just in principle, was metronidazole the appropriate
4 antibiotic, then, to manage the C. diff at the outset?
5 A. I think it was not unreasonable to start with that, in
6 view of guidance at the time. Certainly, when she
7 reached a situation where she was declining to take it,
8 again, you could have considered oral vancomycin and
9 intravenous metronidazole.
10 Q. There came a point, I think, when she wasn't taking the
12 A. Yes.
13 Q. We can go back to the Kardex.
14 A. I think it might be helpful.
15 Q. If we have page 71 back on the screen.
16 MR KINROY: My Lord, may I ask for a little clarification?
17 I didn't quite understand the reasoning:
18 "Answer: ... Certainly, when she reached
19 a situation where she was declining to take it, again,
20 you could have considered oral vancomycin ..."
21 A. If she's declining -- there are sometimes reasons why
22 patients don't like particular medications, and
23 metronidazole orally is not necessarily very pleasant.
24 It has a metallic taste, as well as its notable effect
25 if you drink alcohol with it, but I don't think that was
1 an issue here.
2 I think you could try another oral agent and you
3 might sometimes find that people will take it.
4 Q. I think you do say in your overview report -- and you
5 can correct me if I am wrong -- that metronidazole has
6 a sort of metallic taste --
7 A. That's right.
8 Q. -- that might be unpleasant. What about vancomycin,
9 does that have a sweeter taste?
10 A. I have never taken vancomycin. People don't comment on
11 it in the same way. It is quite acidic.
12 Q. Assuming, then, that the oral route is not -- perhaps we
13 can look at the Kardex, if we can turn to that.
14 I think, if we look at the Kardex, we can see that she
15 receives a full course on the 28th; is that a correct
17 A. I think so. I have trouble with numbers and squiggles
18 in this record, which I think you will see. I don't
19 know whether the circles above the evening dose on the
20 29th and the 1st are a number.
21 Q. The number "3" certainly indicates that the patient
23 A. That is certainly in the nursing records.
24 LORD MACLEAN: I have to confess that I have actually had
25 metronidazole sub nom Flagyl, of course, and I don't
1 recall it being a horrid taste.
2 A. Some people complain of it and some people don't,
3 my Lord.
4 LORD MACLEAN: I'm not even sure it was effective,
5 particularly -- well, I think it probably was. It
6 wasn't in a hospital setting either --
7 A. No.
8 LORD MACLEAN: -- and I didn't know about the drink.
9 A. It is a good cure. Again, that doesn't affect
11 LORD MACLEAN: Oh, right.
12 MR MACAULAY: The circles you mention, it is quite difficult
13 to work out what is within the circles.
14 A. I didn't comment on it in my report because I wasn't
15 aware of its potential significance, but I take from the
16 nursing record on GGC00240046 the note that she was
17 refusing medication at times. I think that is the case,
18 in the nursing notes.
19 Q. It appears she seems to have taken the medication
20 certainly for about two days, and then you say you'd be
21 looking for some other alternatives if she wasn't able
22 to go down the oral route?
23 A. I think you would consider that. It has to be said that
24 a large proportion of patients given metronidazole do
25 not even respond by seven days clinically. So it would
1 be perhaps a bit early to be thinking about vancomycin,
2 but you might have thought about giving it via the
3 intravenous route, metronidazole. She obviously went
4 downhill because they diagnosed her clinically as having
6 Q. She died on 4 February, not long after this.
7 A. On 2 March, I think.
8 Q. Yes.
9 LORD MACLEAN: Yes, I noticed the infection control card was
11 A. Yes.
12 LORD MACLEAN: It said 1 March, perhaps it is the 2nd.
13 A. Yes.
14 MR MACAULAY: SPF00550001. As his Lordship has pointed out,
15 it has been noted here as 1 March. In fact, as we saw
16 from the death certificate, it was 2 March that she
18 A. Yes, I can't recall, but there was certainly one patient
19 who died at sort of 10 minutes past midnight, or
20 something like that.
21 Q. Going to your conclusion, then, Dr Warren, I think here
22 we have a case where the provocative antibiotics were
23 given in the Royal Alexandra Hospital; is that right?
24 A. That's correct.
25 Q. But do you express the view in your conclusion that it
1 is likely -- by no means certain -- that she acquired
2 her infection in ward 14?
3 A. I think it is more than possible from the other cases
4 present at the time and the known potency in disrupting
5 the bowel flora with ceftriaxone, yes.
6 Q. The only other point you make, which is a point we have
7 been discussing, is that she died six days after she'd
8 been unable to cooperate with her oral therapy and had
9 only had three days' treatment. Do you consider that
10 a consultant microbiologist should have been involved to
11 see whether or not another alternative could have been
13 A. I think it is difficult to know from the notes what her
14 clinical condition was, but it might have been
16 Q. The other point, I think, we noted in passing is that
17 there was certainly a delay in starting the medication
18 after the diagnosis had been made?
19 A. Yes.
20 MR MACAULAY: My Lord, I know it is a little bit earlier
21 than usual, but I see it is 3.50 pm. I wonder if that
22 is a convenient point, rather than starting another case
23 and perhaps not finishing. I would be inclined to
24 suggest this might be an appropriate time to adjourn,
25 my Lord.
1 LORD MACLEAN: On Monday, we will be proceeding with
2 Sarah McGinty?
3 MR MACAULAY: I think I will start with Sarah McGinty, if my
4 learned friend Mr Peoples is happy with that.
5 LORD MACLEAN: We will adjourn now until Monday at
6 10 o'clock.
7 (3.50 pm)
8 (The hearing was adjourned until
9 Monday, 5 December 2011 at 10.00 am)
1 I N D E X
3 DR RODERIC ELLIS WARREN (sworn) ......................1
5 Examination by MR MACAULAY ....................1