ARTICLES INTRAVASCULAR CATHETER annually by clinics and hospitals in the USA. 1 This includes more than 5 million central venous and pulmonary artery SEPSIS catheters. Catheter-related infections (CRI) remain among the top three Mervyn Mer causes of hospital-acquired infections, with a mortality of up to 25%, and result in prolonged hospitalisation (mean of 7 days) and increased medical costs.HO The estimated cost of treating lntravascular devices are an integral component of modem-day one episode 01 catheter-related bloodstream infection (CRBS1) medicaJ practice. They are used to administer intravenous in the USA ranged from 58 000 in 1988 to more than 528 000 for fluids, medications, blood products and parenteral nutrition. In intensive care patients in 1994. On the basis of these figures, the addition, they serve as a valuable monitor of the haemo- economic burden from CRBSl is substantial. dynamic status of critically ill patients. Central venous catheters (CVCS) account for an estimated 90% of all CRBSl.lI Rates of bloodstream infection range from 4 BACKGROUND AND HISTORY to 13 per 1 000 central catheter days,n with lower rates in Only a century ago, no means of vascular access existed for the respiratory intensive care units and higher rates in bums units. lile-sustaining support 01 critically ill patients. In the late 1800s Given the magnitude and seriousness of the problem of CRI, steel needles became available, and with the advancing it is essential for health care workers to have a clear knowledge of electrolyte physiology the therapeutic use of understanding of the diagnosis, pathogenesis, prevention and intravenous fluid became established. In 1945, following the treatment of this problem and the new developments in the advent of penicillin and the need for multiple intravenous field. Most of these infections can be reversed with appropriate injections, plastic catheters for continuous vascular access were diagnosis and treatment, and many can be prevented. describedY A further technological advance took place in 1%7 when the placement of long nylon catheters into central veins, FORMS OF CATHETER SEPSIS to limit medication-associated phlebitis, was described in oncology patients.) These catheters were initially inserted by Definitions peripheral cutdown techniques and later via percutaneous approaches into the subclavian and jugular veins. Over the past Definitions relating to intravascular catheter sepsis have been 15 years the focus of research and development has been on the put forward by various workers, but many have complicated physicochemical properties 01 catheters, looking at such aspects matters and been confusing. This has in part related to the fact as improved catheter materials, tensile strength, rupture that definitions used for surveillance and research purposes resistance, biocompatibility and the creation of catheter micro- have diffened from those used lor clinical diagnosis. The environments hostile to invading organisms. Centers for Disease Control and Prevention in Atlanta, Georgia, have suggested sensible definitions1J which allow for the use of Intravascular devices have therefore been a major advance in both clinical and laboratory evidence of catheter sepsis. These terms of patient comfort and care, but with them has come the should be universally used in the definition of intravascular burden of complications, including a variety of local and catheter sepsis and are documented in modified form in systemic infectious complications. Table I. In general, intravascular devices can be divided into those used lor short-term (temporary) vascular access and those used for long-term (indwelling) vascular access. Long-term intravascular devices usually require surgical insertion. while T~le L Definitions for Gltheter-re.lat:ed infections short-term devices can be inserted percutaneously. The main focus of this review relates to short-term catheters. Catheter colonisation.: growth of:;e 15 colony-forming units (semi-quantitative culture) &om a proximal or distaI catheter segment in the absence of local or systemic infection ~GNTnJDEOFTHEPROBLEM Local infection: erythema, tenderness,. induration or purulence within 2 cm of the skin insertion site of the catheter El Although no Specific local statistics are available, more than Catheter-re1ated bloodstre.a.m. infection: isolation of the same 150 million intravascular devices are currently purchased organism (i.e. the identical species as per antibiogram) &om culture (semi-quantitative or quantitative) of a catheter segment and from the blood (preferably drawn from a peripheral vein) of a patient with accompanying clinical symptoms and signs of lntmsitv Can' Unit, johanntsburg Hospital, and Departmmt of Medicine, bloodstream.infection and no other apparent source of sepsis Unrverslty of the Wittl'atersrand, Johannesburg Mervyn Mer, MB BCh, Dip PEC (SA), FCP (SA) October 1999, VolIS, No. 2 SAICC P ATHOGENESIS OF CATHETER-RELATED DIAGNOSIS OF CATHETER-RELATED SEPSIS INFECTIONS Establishing a diagnosis of CRI involves both clinical and The skin around the insertion site is the most common portal of laboratory components. The clinical features are generally entry. I .. ,.. The current Wlderstanding is that a fibrin sheath nonspecific and indude fever, rigors, hypotension and develops around the catheter which promotes the adherence of confusion. If there is no apparent source of sepsis in a patient pathogens. This is referred to as the biofiJrn layer. Skin with an intravascular line (especially a central venous catheter) organisms then migrate from the skin insertion site along the and if the sepsis appears to be refractory to antimicrobial external surface of the catheter to colonise the distaI therapy or is of abrupt onset and associated with shock. the intravascular tip and ultimately cause bloodstream infection. possibility of line-related sepsis needs to be considered. Contamination of the catheter hub during its manipulation by Fundoscopy should always form part of the clinical medical and nursing personnel is the second most common examination as focal retinal lesions are common in patients portal of entry of micro-organisms. These organisms migrate \vith CVC-derived Candida infection, even when blood cultures along the internal surface of the catheter leading to luminal l are negative. Inflammation or purulence at the catheter colonisation and thence to bloodstream infection. u,.l7-1!1 Although insertion site is seen in less than hall the cases. much less common than either of the above two mechanisms, The laboratory components include culture of blood and the haematogenous dissemination from a distal infectious focus or catheter. Blood cultures ;,re central to the diagnosis of CRBSI. administration of contaminated infusate may also cause CRI.1lUl Two to three 10 m.l samples, ideally from separate peripheral Other sources such as contaminated transducer kits, venipuncture sites, should be sent to the laboratory. Paired disinfectants and infusion lines are also rare causes. quantitative cultures, which involve taking blood from both the catheter and a peripheral site, may be particularly useful where MICROBIOLOGICAL PROFILE OF CATHETER- luminal colonisation is predominant. The diagnosis is RELATED INFECTIONS (TABLE m suggested when fivefold or more colonies are isolated from the blood drawn from the vascular catheter as compared with the The microbiology of CRI reflects a predominance of skin concurrent peripheral sample.1i1:UJ organisms such as Staphylococcus epidermidis, S. aureus, Bacillus species and Corynebacterium species (especially JK strains). jK The most widely used laboratory teduUque for culturing the bacteraemia occurs almost exdusively in severely catheter is the semiquantitative roll-plate metho(pt In this immunosuppressed patients who are or have been receiving method, cultures are obtained from a segment of the catheter broad-spectrum antibiotics and who have indwelling after it has been removed from the patient by rolling the intravascular devices. catheter segment across the surface of a blood-agar plate at least four times and then determining the number of colonies present after a period of incubation. Growth of ;;;: 15 colony- Table n. Common organisms ~ed with atheter--re1at:ed forming units from a proximal or distal catheter segment is infections . regarded as significant. Quantitative teduUques for culturing Staphyloa>ccus epidmnidis Enterobactu species the catheter include the sonication and vortexing methods, 5. aulTUS Serratia rrrtlTasan5 which involve extracting micro-organisrns from the catheter Cmuiida species Citro/><ldrr Jmutdii surface into a medium for culturing. This entails either flushing Arinetobocter species Enterococcus species out the catheter segment and immersion in culture medium or Pseudomoruls tletUginosa Bacitlus species placement of the segment in culture medium with Stenatrophomonas maltoplu1ia Caryntbaderium (especially JK Klebsiella species strains) sonication.m73 Quantitative culture is the most sensitive technique for diagnosis of catheter-related infection. Other techniques such as Gram staining of the catheter surface and culture of the tip in broth are associated with high false- positive rates. A newer diagnostic culture technique is that of Contamination from the hands of medical and nursing the endoluminal brush. This allows samples to be taken via the personnel is frequently responsible for infection with such lumen of the catheter with a brush while the catheter remains organisms as Pseudomonas aeruginosa, Acinetobacter species, in situ. A sensitivity of 95% and a specificity of 84% in the Stenotrophomonas mllitaphilia and Candida species.c.:~ diagnosis of CRI has been reported with this teduUque. 3 -" This Emerging pathogens, including species of Enterococcus, technique does not require sacrifice of the cathet~ but there is Micrococcus and Achromobacter, rapidly growing mycobacteria still a delay before culture results are known. There are also such as Mycobacterium Jorhlitum and M. chelonei, and fungal concerns that the process of brushing may lead to embolisation organisms such as Malassezia furfur, Rhodotorula species, of infected. biofilm. The place of the endoluminal brush in Fusarium species, Trichosporin species and Hansenula anomala clinical practice is still to be determined. have also caused catheter infections.l~ ARTICLES J PREVENTIVE STRATEGIES FOR CRI Silver-chelated subcutaneous collagen cuffs Strict adherence to halldwashing and aseptic technique remains the These cuffs may be attached to percutaneously inserted CVCs comeTstone of prevention of CRI. However, other measures may and are designed to act as both a mechanical barrier to the confer additional protection and need to be considered in the migration of micro-organisms and an antimicrobial deterrent preventive strategy. These include infusion therapy teams, use (through the effect of silver ions). They have been shown to of barrier precautions during catheter insertion, cutaneous lower the risk of catheter colonisation and CRBSI in critically ill antimicrobials and antiseptics, site of catheter insertion, patients.X'.JI The anti-infective effect is short-lived, however, as tunnelling of eves, silver-chelated subcutaneous collagen the collagen to which the silver ions are chelated is cuffs, antiseptic hubs, catheter-site dressings and the use of biodegradable. Other drawbacks include cost and the need for antimicrobial impregnated catheters. specialised training. Infusion therapy team Antiseptic hubs The presence of an experienced infusion therapy team whose These have been designed to protect against hub colonisation. task is to insert and maintain catheters has been shown to A fourfold decrease in catheter-related sepsis has been decrease the rate of eRBSI up to eightfold and limit overall demonstrated with their use.:J9 A major limitation, however, is costs.J1.J::! Similarly, strict adherence to peotocals for catheter that protection is only conferred against organism migration insertion in the intensive care unit (lCU) and theatre are also along the internal surface of the catheter. They do not protect beneficial in decreasing the rates of CRI. against the migration of skin organisms along the external surface. Maximum sterile barriers Dressings Careful hand washing together with the use of sterile gloves, a mask. gown and cap and a large drape have been associated There has been ongoing debate concerning the best method of with a greater than sixfold decrease in eve-related sepsi? catheter dressing. This has essentially revolved around the and a fourfold decrease in the rate of bacteraemia related to relative merit of gauze and tape dressings versus transparent pulmonary artery catheters." The use of this practice cannot be films. In a meta-analysis of catheter dressing regimens, eves over-emphasised. on which a transparent dressing was used were assoriated with a significantly higher incidence of catheter tip colonisation but Cutaneous antimicrobials and antiseptics a non-significant increase in CRBSI..jD Given the important role of cutaneous microflora in the The preference in our unit is an adhesive gauze dressing pathogenesis of catheter-related infections, measures to reduce with a central non-adherent pad. cutaneous colonisation of the insertion site are of vital importance. Antimicrobial coating of catheters For skin decontamination before catheter insertion in a three- In recent years, antimicrobial substances have been effectively group trial.il comparing the efficacy of treatment, 2% bonded to catheters, especially those designed for short-term ch10rhexidine gluconate was associated with a fourfold use. Two coated cves are currently available, a decrease in CRBSI as compared with 10% povidone-iodine and chlorhexidine/ silver sulphadiazine catheter and a 70% alcohoL The use of PNB ointment (polymixin-neomycin- minocycline/rifampicin catheter. Several studies have shown badtradn) at the skin entry site has been associated with a potential benefits of such catheters in terms of reduction of lower rate of CRBS!; however, the overall protective effect is catheter colonisation as well as CRBSLuo,.u-c offset by a higher risk of fungal colonisation and infecti.on.l3 A potential drawback of the chIorhexidine/silver It is the practice in our unit to use a chlorhexidine gluconate- sulphadiazine catheter, however, is that the coating is applied containing solution for skin preparation. only to the external surfaces and does not protect against endoluminal colonisation as a result of hub contamination. The Tunnelling of evCs minocycline / rifampicin catheter is coated on both the external lIB This involves placing the proximal segment of the catheter and internal surfaces and may therefore be more effective." One of the concerns about the use of antimicrobial- under the skin at a distance from the point of entry to the vein. impregnated catheters relates to the possible development of A lower rate of CRBSI has been reported in one study in antimicrobial resistance, and where they are used continued critically ill patients.J6 More data are required to support this observation. surveillance for resistance is required. October 1999. Vol. 15. No. 2 SAJCC ARTICLES TREATMENT PRINCIPLES OF CATHETER- Central venous catheters RELATED INFECnON cves account for an estimated 90% of all CRBSI. on- Treatment depends on the stage of infection and the pathogen. tunnelled (percutaneously) inserted CVCS are the most As a general rule if CRBSI is suspected the catheter must be l commonly used central catheters. A host of risk factors for removed and replaced only if necessary. Most of the infectious evC-related infections have been reported, induding duration complications are sell-limited and resolve after removal of the of catheterisation,. location of the catheter (the internal jugular catheter. having a higher rate of CRI than the subclavian vein), the Indications for antibiotic therapy include persistent sepsis presence of sepsis, type of dressing, multi-lumen catheters despite catheter removal, evidence of septic thrombosis of the (increased frequency of manipulation), less stringent barrier great veins, clinical or echocardiograpruc evidence of precautions during placement, experience of personnel endocarditis, metastatic foci of infection.. underlying valvular inserting the device, and the administration of parenteral heart disease (especially prosthetic valves), and an underlying nutrition. immunosuppressed state. The duration of evc use remains controversial. Despite this, In terms of specific pathogens and CRBSI, S. aUTellS and however, no catheter should be left in place longer than Candida species require special mention. In the setting of absolutely necessary. ThE:' duration of catheterisation has been shown to be a risk factor for infection in several studies!C·S!; and uncomplicated S. Qureus eRBSI, the cathe~er should be removed and 2 weeks of parenteral antibiotics given. There is a scheduled replacement remains widely practised in most ICUs. high relapse rate if these are given for a shorter time.e.~ In a recently performed study in mainland Britain, where 165 ICUs were surveyed,>6 catheters were routinely replaced, the Systemic antifungal therapy (together with removal of the mean time being 6.5 days. catheter) should be given in all cases of catheter-related candidaemia in view of the potentially significant sequelae. 11 We have recently completed and analysed a evc study in Amphotericin B or fluconazole (except for fluconazole-resistant the multidisciplinary lCV at Johannesburg Hospital. The study organisms such as Candida glabrata and C. krllsei) should be was a prospective randomised double-blind study which commenced. Fluconazole 400 mg daily for at least 14 days has entailed comparison of a 14-day placement of standard triple- lumen versus antimicrobial-impregnated (chlorhexidinelsilver been shown to be as effective as amphotericin B 0.5 mg/kg/d sulphadiazine) cves on the rates of CRI. Our aim was to for 14 daysl with fluconazole being less toxic.-li determine whether we could safely increase the duration of insertion time from 7 days to 14 days and the influence of the SPECIFIC CATHETER TYPES AND INFECT10 antimicrobial-impregnated catheter on the incidence of CRI. One hundred and eighteen critically ill patients were Short peripheral intravenous catheters included in the study, which spanned 3-1951.5 catheter hours (1 These remain the most commonly used intravascuJar devices. 456 catheter days). Sixty-two patients received a standard There is a significant risk of contamination 72 hours after catheter and 56 an antimicrobial·impregnated catheter. insertion.fi The insertion site should be an upper extremity or Eighteen of the patients developed a CRBSI, 1 of whom died, the external jugular vein. There is a greater risk of infection and 5 patients demonstrated catheter colonisation. This rate of with lower extremity sites and "vith cutdowns. CRBSI compares favourably with those previously reported, in which many of the catheters were in place for shorter periods Peripheral arterial catheters of time than in our study.lU9 Peripheral arterial catheters are associated with less infection The most frequent source of infection was the skin.. followed than pulmonary artery catheters (PACsl, CVCs and short by hub and infusate contamination and lastly haematogenous peripheral catheters.~ This may be explained by high arterial seeding. The source; and organisms were identified with the flow around the catheter, which probably decreases the aid of restriction-fragment length DNA subtyping. adherence of micro-organisms.sl The Centers for Disease We were unable to show any difference in CRJ rates behveen Control and Prevention guideline u suggests that replacement the two types of catheters in the study. Most importantly we of catheters and relocation of insertion sites need take place no were able to condude that standard cves can safely be left in more frequently than every 4 days. place for 14 days (with stringent infection control measures). It is our unit policy to keep peripheral arterial catheters in Parenteral nutrition was not noted to be a risk factor for place for up to 30 days prior to replacement and relocation, catheter sepsis, and neither was the site of insertion (internal unless otherwise indicated. jugular vein versus subclavian vein). On the basis of the results of this study, it is now our practice to keep standard cves in place for 14 days unless there is an ARTICLES Peripherally inserted central venous catheters Table ID. Protocol for inse.rt:ion of central venous catheters (PICes) • Oean the skin around the insertion site over a wide area by rubbing for 2 minutes with sterile gauze or rottonwool PICCs provide an alternative to subclavian or jugular vein soaked in a ch.Iorhexidine gIuconate-containing solution. catheterisation and are inserted into the superior vena cava or Sterile gloves must be worn.. right atrium \ria the cephalic and basilar veins of the • The doctor,. wearing a mask and Gip, scrubs up (using a antecubital fossa. Compared with other cves they are chImhexidine gluconate-rontaining scrub solution) and then associated with few mechanical complications, an apparent dons a sterile gown and gloves. lower rate of infectionl',oll and decreased cost. The length of • 1he doctor then deans the area again and drapes widely to time that these catheters can be left in place safely has not yet include the patienrs head, neck. chest,. limbs and torso down to the pelvis. Only the portion necessary for catheter insertion been determined, although they have been used successfully should be left exposed. for extended periods. • The 'flush' (heparin 1 (XX) ill in 19 ml sterile saline) is drawn up avoiding any contamination by the doctor after cleansing G uidewire exchanges of the stopper on the heparin container. The doctor draws up the 'flush' with a sterile syringe and needle, while the A recent meta·analysis of evc replacement strategies revealed assistant holds the vials. that guidewire exchanges were associated with greater risk of • Once the line has been inserted, a sterile piece of gauze CRI but fewer mechanical complications than new-site soaked in a chlorhexidirle gluconate-containing solution is replacement.51 If guidewire exchange is used. metirulous applied over the insertion site and adjacent area for aseptic technique is necessary. This procedure should not be approximately 30 seconds. perfonned in the setting of confirmed or clinically suspected • The area is then dried with sterile gauze and an adhesive sepsis. In our unit we do not practice guidewire exchanges. gauze dressing with a central non-adherent pad applied. • The dressings are changed daily and the insertion site inspected and cleaned in a sterile manner. Cleaning includes AOOITIONAL RECOMMENDATIONS TO LIMIT removal of old blood, dots, exudates and crusts and the INFEcrION application of a chIomexidine gluconate-soa.ked piece of sterile gauze to the insertion site for approximately 30 On the basis of the results of our study, previous guidelines13 seconds, before drying and dressing the area and the cumulative anecdotal experience in our unit, both • Any signs uf local infection (red. hot, swollen. painful, nursing and medical, we now have a dedicated policy purulence) must be reported. regarding the insertion, maintenance and use of intravascular devices. The basic principle revolves around strict adherence to aseptic technique at all times. It is our present policy to change indication for earlier removal. This practice goes hand-m-hand central venous and haemodialysis catheters after 14 days, with a stringent protocol relating to aseptic insertion technique peripheral venous catheters after 3 days and arterial lines after and care of the catheter. A modified fonn of this protocol 30 days, unless removal is indicated beforehand. Lines used for appeiUS in Table ffi. the administration of blood products must be replaced. within 24 hours. [jpid-containing parenteral nutrition solutions Pulmonary artery catheters should be completed within a 24-hour period. Parenteral Varying rates of infection have been reported with PACs nutrition must be administered via a single dedicated port with (Swan.(;anz catheters), but most are similar to CVCs. Where the administration line being replaced at 24-hour intervals higher percentages have been reported, this has been attributed (performed as a sterile procedure). Administration sets such as to the number of manipulations performed. The 'Hahds-Off those used. for the delivery of inotropes and antibiotics are Catheter', which is endosed in a contamination·proof shield replaced at 72·hour intervals, or before if clinically indicated. enabling the doctor to prepare, test and insert it without The day on which lines are changed should be dearly noted on exposure to external contamination. has been associated with a the rcv chart decrease in systemic infection.~ Most PACs are heparin- It is our policy to replace bridges and their attached lines, bonded, which reduces catheter thrombosis and microbial transducers and continuous flush devices every 7 days. This is m:I adherence." The current Centers for Disease Control and longer than the recommended %-hour interval,u but it is our Prevention guideline recommends catheter replacement at least experience that provided there is strict adherence to aseptic every 5 days. U It is our current practice to keep in PACs for up technique, the infection risk is not increased. Aseptic technique to 7 days if necessary; by which time the patient &equently no also extends to care of ports and caps attached to intravasrular longer requires this form of catheter. devices and includes the spraying of a chlomexidine gluconate- containing solution following manipulations. October 1999, Vol1S, 0.2 SAJCC 34..Mm DC. Ringer M. Alvando q. Prospective randomised trial of p m ~ 31ooho1 CONCLUSION and chknhexidine for p......."tion of infa1ions ~ with Q5ltral venous and IlI12rial ca.theters. Lmat 1991; J38: 339-343. Intravascular catheter-related ~psis remains a major problem. 35. Maki OC. Band JO. A <Dm.parative study of polyantibioticand iodopher oirttmaIts in preo..entioo. of vascular catheter-relared infection. NIl I Mtd 1961; 7Q: 739-744. Stringent adherence to aseptic technique and infection control 36. TunsitJ-F. 5ebille V, Fadas J-C. rt lI1.. 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Gm MaJ As5Dc J 1967; 96: 94-97. on the preYention of ca.theter-rel.ated ~is using a new hub model J\Jut S"''i 1996; 213; 363- 4. Maki DG. 11Ifrdi<m CIl...w Iry ,..hvr1tIscu!aT Ckui«5: p,.~, Stnrkgios for Prn>crn-. 369. London: RoyaI5ociety of Medicine Servi<.Es. 1991. 40. Hoffman KK. Weber DJ, Samsa GP. Rutala WA Transparent po!yunothane film as an 5. Smith R4 ~ 5M.. 5imbedoff MS. Excess mortality in critically ill patients with intrave<lDlJ"> ~ dnos6ing: a meta-analysis cl the infection risks.. lAMA 1992; Ut7: 1I'!l2- nosocomial. bloodstream infections. C1IlSt 1991; 100: 16+-167. 2ll7. 6. Martin MA. Pf<iller MA. WenZ2I. RP. ~tivt,> staphylocDcc:al 41. s. Civetta JM. H~J. Ball De<::rea$ing catbet2r-rel.ated and hospital <XI5l$ by ~ Mortality and hospital stay. A1UIlrrtDn Md 1989; UO: 9-16- continuous quality imPrD\'el\ent. Crit GIrl' Mtd 1996;!'l: 166().I665. 7. Haley RW, Schabefg OR, Van Allmm. SO, McGowan JE jun. Estimating the extra d1a:Be5 and 42. Raad L Oarouiche R,. Ha<:hem R. Mansouri M. Bodey Gp. The broad spectrum adivity and prolongation of hospitalization d~ to /IOI:IOCOlD.ial infections: a comparison of mi'thods. / effiGlC}' of calheter5 mated with minocydine and rifampicin. I Infrd Vis 1996; 17.1: 4]8424.. mfrct Vis 1980; 141: 248-2:>7. 43. Raad L OarouIche R. Dupui:s J, d fll. Central VenolG ca.theters cooted with IIIinocvdine and 8. Pillet D. Torrara 0, WenzeI RP. Nosocomial bloodstream infection in critiGilly ill patients: rifampKin for the pre-vmtion of catheter relared cokxtizatiDn and bIood-weam We.:oon. Ann ex~ Imgth of stay. extra C05t5 and attributable mortality. JAMA l~ Z71; 1596-1601. (n.!ern Mtd 19'97; 121: 267-Z74_ 9. Arrow PM. Qu.im<Sng EM, Brech M. Consequ~ of intravascular catheter sq>sis. Oin 44.. Darouiche RO. Raad Il,. Heard SO. rt al. A comparison of two antimicrobial-impregnah.'d fnfrrt Dis 1993; 16: 778-784-. e=traI verIOUSalherers. N Engt J....!t'd 1999; 34Q: 1-8. 10. HeiseInml D. Nosoromial bloodstream um..Don5 in the aitica11}' ill.1AMA 1994;?n; 1819- 45. Raad It Sabbagh MF. Optimal duration of thatpY for catheter-related ShIpIry!oa:lm<.s llllml$ bacteremia: a study of 53 cases and review. Rn> Irrf«/. Vis 199'2; It: 75-82- IJl2ll 11. Mak:i DG. Irtfe<:tioo5; dUI' 10 infusion ther3py. In: Ilertn<!I:t IV. erachman PS, eds- H">pitw 46. Malano!W GJ. Samure 1.1H, Pefanis A. I<arduner AW. Shlplryloaxcu5 llUrtuS ~ blfrctim5. 3nl ~ Boston, Mass:: little. Brown. 1992. associated b3cteremia: minimal effective therapy and unusual infuctious axnplicatiDns associated with artviaI shmth catheter$. ArdIl"fun MLJi 1995; 155: 1161-1166- 12. National No5ocDmiallnfections Surveillanc:e (NNIS) Systo= report. data ~ from 0dDber 1956 _April 1998. i.ssua!d June 1996. Am Jlrrf«t Contl'lllI9'J8; 26: 522-533. 47. Rose HD. Venous catheter-associated candidemia. Am I MftI sa 1978; 215; 265-269. 48. Rex JH.Benr.otI lE. Sugar AM. d fll. 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