Comment on Guidelines for the antibiotic treatment of endocarditis by ltq19768



Journal of Antimicrobial Chemotherapy                                             Journal of Antimicrobial Chemotherapy
doi:10.1093/jac/dki187                                                            doi:10.1093/jac/dki188
Advance Access publication 9 June 2005                                            Advance Access publication 9 June 2005

Comment on: Guidelines for the antibiotic                                         Endocarditis guidelines: authors’ response
treatment of endocarditis in adults: report of                                    John D. Perry* on behalf of the Working Party of the
the Working Party of the British Society for                                      British Society for Antimicrobial Chemotherapy
Antimicrobial Chemotherapy
Pramod M. Shah*                                                                   Department of Microbiology, Freeman Hospital, Newcastle-
                                                                                  upon-Tyne, UK
Klinikum der Johann Wolfgang Universitaet, Zentrum der
inneren Medizin, Schwerpunkt Infektiologie, Theodor-Stern-                        Keywords: antibiotic therapy, guidelines, endocarditis, BSAC
Kai 7, D-60590 Frankfurt am Main, Germany
Keywords: antibiotic therapy, guidelines, endocarditis                            Sir,
                                                                                  Professor Shah1 has questioned the recommendation2 for an MIC
*E-mail:                                                 determination to be performed on strains isolated from cases

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                                                                                  of infective endocarditis (IE). When considering the need for
                                                                                  MIC determination, one has to consider the nature of the infecting
Sir,                                                                              microorganism, the antimicrobial under test and the reliability of
In these guidelines,1 the authors recommend that ‘A minimum                       any alternative methodology.
inhibitory concentration (MIC) . . . should be established by a stand-               It has been stated that disc susceptibility testing is often
ardized laboratory method to ensure susceptibility.’                              adequate to determine susceptibility for bacteria causing IE,3,4
   What evidence is available that MIC determination                              however the choice of disc susceptibility method is often not stated
improves patient care and outcome or influences the treatment?                    or discussed. For example, many laboratories in the UK now use
I know of one presentation at the European Congress for Clinical                  the BSAC Standardized Disc Susceptibility Testing Method.5
Microbiology and Infectious Diseases by Walton et al.2 from                       However, guidelines for testing a-haemolytic streptococci,
University College London Hospitals who analysed 129 cases of                     which remain the leading cause of native valve IE, were not
endocarditis and concluded that ‘Antibiotic treatment in endocar-                 available at the end of 2004, which leads to questions as to how
ditis can be safely chosen on the result of disc sensitivity testing              such tests might be interpreted. Moreover, the BSAC Working
and adjusted on clinical grounds without MIC.’ The same                           Party2 and other authorities,6,7 recommend therapeutic regimens
group3 recently published analysis of 125 patients admitted                       for a-haemolytic streptococci that vary according to the MIC
between 1981 and 1999 in whom the MIC had been measured.                          for the causative strain.
Their conclusion is inconclusive: ‘The measurement of MIC                            Other examples exist where disc susceptibility methods may
appears prognostically important in deciding the surgical manage-                 not be appropriate, for example, in assessing the penicillin
ment of endocarditis.’                                                            susceptibility of enterococci.8 The determination of glycopeptide
   Can the experts who formulated the guidelines provide some                     susceptibility in enterococci remains problematic as shown
evidence for their recommendation, please?                                        in recent surveys9,10 and the emergence of staphylococci with
                                                                                  intermediate resistance to glycopeptides in cases of IE is likely
                                                                                  to provide a further challenge to the diagnostic laboratory in
                                                                                  future years.11
References                                                                           Professor Shah cites the report of Walton et al.4 who performed
   1. Elliott TSJ, Foweraker J, Gould FK et al. Guidelines for the antibiotic     a case study to examine the contribution of the MIC to the decision
treatment of endocarditis in adults: report of the Working Party of the British   to treat endocarditis surgically. The authors concluded that a
Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2004;              moderately elevated MIC of flucloxacillin may be associated with
54: 971–81.                                                                       failure of medical treatment, when flucloxacillin is used, even
   2. Walton B, Wallace S, Kharbanda R et al. Is minimum inhibitory               in combination. They also agreed that the MIC of penicillin for
concentration (MIC) useful in endocarditis? In: Program and                       a-haemolytic streptococci was useful in determining length of
Abstracts of the Tenth European Congress of Clinical Microbiology                 treatment. Such findings support MIC determination for strains
and Infectious Diseases, Stockholm, Sweden, 2000. Abstract TuP7.                  causing IE and further studies that examine the relationship
European Society of Clinical Microbiology and Infectious Diseases,                between MIC and treatment outcome are warranted.
Basle, Switzerland.
                                                                                     In conclusion, we accept that for some organism/antimicrobial
   3. Walton BI, Wallace SM, Kukreja N et al. Is the MIC useful in deciding
                                                                                  combinations, disc susceptibility testing may be adequate for guid-
to treat endocarditis surgically? Int J Antimicrob Agents 2004; 23:
                                                                                  ing therapy, however, our consensus opinion is that our general
                                                                                  recommendation to perform MIC testing is justified. IE remains
                                                                                  an uncommon disease with high mortality in which the choice and
                                                                                  duration of therapy are critical to a successful outcome. Also, if
                                                                                  MIC testing is considered by some laboratories to be technically


demanding, the availability of the Etest methodology provides an                  Keywords: antimicrobial resistance surveillance, macrolides,
alternative option for MIC testing.                                               Streptococcus pneumoniae, antibiotic usage

                                                                                  *Corresponding author. Tel: +45-3268-8190; Fax: +45-3268-3231;
References                                                                        E-mail:
    1. Shah PM. Comment on: Guidelines for the antibiotic treatment                Present address. Clinical Unit for Health Promotion, H:S
of endocarditis in adults: report of the Working Party of the British Society     Bispebjerg Hospital, Copenhagen, Denmark
for Antimicrobial Chemotherapy. J Antimicrob Chemother 2005; 56:
    2. Elliott TSJ, Foweraker J, Gould FK et al. Guidelines for the antibiotic    Sir,
treatment of endocarditis in adults: report of the Working Party of the British   We would like to comment on the article entitled ‘Meta-analysis
Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2004;
                                                                                  of bacterial resistance to macrolides’ by Halpern et al.1 The idea of
54: 971–81.
                                                                                  a meta-analysis of published studies on resistance is interesting.
    3. Eykyn SJ. Infective endocarditis: some popular tenets debunked?
Heart 1997; 77: 191–3.
                                                                                  However, it does not add much to our knowledge on the prevalence
    4. Walton BI, Wallace SM, Kukreja N et al. Is the MIC useful in
                                                                                  of macrolide resistance. Pooling the results of randomized studies
deciding to treat endocarditis surgically? Int J Antimicrob Agents 2004;          is a method to assess treatment efficacy. However, it does not make
23: 394–7.                                                                        sense to use it for resistance, since the reported prevalences in
    5. Andrews JM. BSAC standardized disc susceptibility testing method           different studies depend almost solely on local factors and the

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(version 3). J Antimicrob Chemother 2004; 53: 713–28.                             results could be misleading for readers and prescribers in many
    6. Horstkotte D, Follath F, Gutschik E et al. Guidelines on prevention,       countries with low prevalence of resistance.
diagnosis and treatment of infective endocarditis executive summary; the              The first problem with this meta-analysis is publication bias. We
task force on infective endocarditis of the European Society of Cardiology.       disagree with the authors on their view that: ‘Given the nature of
Eur Heart J 2004; 25: 267–76.                                                     this topic, it is likely that there would be equal interest in reports of
    7. Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment              low or high levels of resistance’. Countries with low resistance
of adults with infective endocarditis due to streptococci, enterococci,           rarely feel the need—or are even able—to publish their results in
staphylococci, and HACEK microorganisms. JAMA 1995; 274:                          peer-reviewed journals, but rather quickly report at national level.
                                                                                  In Denmark and Sweden, this is done within 6 months of the end of
    8. Snell JJ, Brown DF, Perry SF et al. Antimicrobial susceptibility test-
                                                                                  a calendar year, e.g. data for 2003 were published in June 2004.2,3
ing of enterococci: results of a survey conducted by the United Kingdom
National External Quality Assessment Scheme for Microbiology. J Anti-
                                                                                  However, most peer-reviewed publications take somewhat longer,
microb Chemother 1993; 32: 401–11.                                                thus delaying report to prescribers. As mentioned by Halpern et al.,
    9. Potz NA, Mushtaq S, Johnson AP et al. Reliability of routine disc          the meta-analysis only confirms results that were already available
susceptibility testing by the British Society for Antimicrobial Chemotherapy      from multinational surveillance studies such as PROTEKT. More-
(BSAC) method. J Antimicrob Chemother 2004; 53: 729–38.                           over, the view of resistance it offers is already out of date since
   10. Hageman JC, Fridkin SK, Mohammed JM et al. Antimicrobial                   more recent data are available from multinational surveillance
proficiency testing of National Nosocomial Infections Surveillance                projects, e.g. the European Commission-funded European
System hospital laboratories. Infect Control Hosp Epidemiol 2003; 24:             Antimicrobial Resistance Surveillance system (EARSS; http://
356–61.                                                                  or PROTEKT, national reports, e.g. DANMAP2
   11. Leung KT, Tong MK, Siu YP et al. Treatment of vancomycin-                  and SWEDRES,3 or abstracts at international conferences. The
intermediate Staphylococcus aureus endocarditis with linezolid. Scand             meta-analysis included very few studies from some regions of
J Infect Dis 2004; 36: 483–5.                                                     the world, raising the possibility that the exclusion criteria used
                                                                                  were too stringent. For example, there are many data from Canada,
                                                                                  a country with relatively low, but increasing, macrolide resistance.
                                                                                  It is unclear why countrywide data on isolates tested centrally by
Journal of Antimicrobial Chemotherapy                                             the Canadian Bacterial Diseases Network4 were excluded. The
doi:10.1093/jac/dki215                                                            reasons for exclusion may be that they only covered a short
Advance Access publication 20 June 2005                                           time period and were not stratified by age and condition. However,
                                                                                  the meta-analysis failed to report results stratified on these criteria.
High prevalence of macrolide resistance: not in                                   As it is the norm when performing meta-analyses, e.g. to assess
                                                                                  treatment efficacy, Halpern et al. should have contacted the authors
every country! [Comment on: Halpern et al.                                        of published surveillance studies for more detailed and updated
J Antimicrob Chemother 2005; 55: 748–57]                                          resistance data. For other regions in the world, reliable resistance
Dominique L. Monnet1*, Christian T. Brandt1, Margit S.                            data simply do not exist and the money invested in the meta-
                                                                                  analysis may have been better used for performing studies in
Kaltoft2, Line Bagger-Skjøt1, Thomas L. Sørensen1†,
                                                                                  those regions where data are crucially missing, i.e. Africa, many
Hans-Ulrik K. Nielsen1 and Niels Frimodt-Møller1                                  parts of Asia, and Central and South America.
                                                                                      Because of the relatively small number of studies included in the
  National Center for Antimicrobials and Infection Control,                       meta-analysis, results could not be presented for each year and each
Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S;                     country. Consequently, the meta-analysis only reported on pooled
  Streptococcus Unit, Statens Serum Institut, Copenhagen,                         results for 1997–2003, whereas EARSS, as well as national
Denmark                                                                           sources,2,3 show that macrolide resistance varied during this period.


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