Pediatr Nephrol (2004) 19:1324–1333DOI 10.1007/s00467-004-1596-8

R E V I E W

Fabio Paglialonga · Susanna Esposito ·Alberto Edefonti · Nicola Principi

Catheter-related infections in children treated with hemodialysis

Received: 10 February 2004 / Revised: 15 June 2004 / Accepted: 24 June 2004 / Published online: 17 September 2004� IPNA 2004

Abstract Infectious complications of the central venouscatheter (CVC) are a major source of morbidity amongchildren treated with hemodialysis (HD), with catheter-related bloodstream infections (CRBSI) being the mostimportant clinical manifestations. As only a few studies ofchildren on HD have been published, the management ofCVC-related infections in this population is mainly basedon data derived from adults or occasionally from childrennot affected by end-stage renal disease (ESRD). The aimof this review is to discuss current knowledge concerningthe epidemiology, prevention, and treatment of catheter-related infections in children on HD. Catheters impreg-nated with antibiotics/antiseptics, lock antibiotic prophy-laxis, nasal mupirocin, and the application of ointments atthe exit-site have all been proposed as means of reducingthe risk of CVC infections, but their real efficacy in thepediatric population has not yet been demonstrated. Fur-thermore, it is not clear how long antibiotic therapyshould be continued, and there is still debate as to whetherthe catheter has to be removed. We propose some prac-tical guidelines for the management of CRBSI in childrenwith percutaneously inserted and surgically implanted HDcatheters, but a number of unresolved clinical issues stillremain, which will require prospective clinical trialsspecifically performed in pediatric patients with ESRD.

Keywords Catheter-related infections · Hemodialysis

Introduction

Central venous catheters (CVCs) are frequently used asvascular accesses in pediatric patients treated with he-modialysis (HD) [1, 2, 3]. In the short term, they representa feasible option for children with acute renal failure oruntil an arteriovenous fistula is ready to use [1, 2, 3]. Inthe long term, they are frequently needed because of thedifficulty in establishing or maintaining a permanent vas-cular access [1, 2, 3].

Infections are major complications of CVCs, withcatheter-related bloodstream infections (CRBSI) beingthe most important clinical manifestations, frequently as-sociated with access loss, severe metastatic infections,and, occasionally, even death [4, 5, 6]. As only a fewstudies of children on HD have been published, the ap-proach to CVC-related infections in this population ismainly based on data derived from adults, or occasionallyfrom children not affected by end-stage renal disease(ESRD) [7, 8, 9, 10]. This has led to considerable het-erogeneity of behavior in different pediatric nephrologycenters and a number of questions related to the preven-tion and treatment of CRBSI remain open [11]. The aimof this review is to discuss current knowledge concerningthe epidemiology, prevention, and treatment of catheter-related infections in children on HD.

Definitions and diagnosis

The contrasting results reported by different authors arefrequently due to the lack of uniformity in criteria used todiagnose CVC-related infections. According to the mostrecently published guidelines, CRBSI have to be definedas bacteremia or fungemia in a patient who has an in-travascular catheter and at least one positive blood cultureobtained from a peripheral vein, clinical manifestations ofinfections (i.e., fever, chills, and/or hypotension), and noapparent source of infection other than the catheter [7, 8,9, 10]. One of the following should be present: a positivesemi-quantitative (�15 cfu per catheter segment rolled on

F. Paglialonga · S. Esposito ()) · N. PrincipiInstitute of Pediatrics,University of Milan,Via Commenda 9, 20122 Milan, Italye-mail: Susanna.Esposito@unimi.itTel.: +39-02-57992498Fax: +39-02-50320226

A. EdefontiNephrology and Dialysis Unit,Istituti Clinici di Perfezionamento,Milan, Italy

a culture plate) or quantitative culture (�102 cfu percatheter segment processed in broth and sonicated) inwhich the same organism (species and antibiogram) isisolated from the catheter segment and a peripheral bloodsample; simultaneous quantitative blood cultures with a�5:1 CVC/peripheral blood ratio; or a differential time topositivity (i.e., a positive culture from a CVC obtained atleast 2 h before a positive culture from peripheral blood)[7, 8, 9, 10].

Moreover, catheter colonization has to be consideredas the growth of organisms from a catheter segment in asemi-quantitative or quantitative culture [7, 8, 9, 10].Accordingly, exit-site infection has to be defined as thepresence of erythema, tenderness, induration, or puru-lence within 2 cm of the exit-site, whereas tunnel infec-tion is characterized by tenderness, erythema, and/or in-duration >2 cm from the exit-site along the subcutaneoustract of a tunneled catheter with or without concomitantbloodstream infection [7, 8, 9, 10]. Finally, pocket in-fections are characterized by infected fluid in the subcu-taneous pocket of a totally implanted intravascular device,often associated with tenderness, erythema, and/or indu-ration over the pocket, whereas phlebitis can be defined asinduration or erythema, warmth, and pain or tendernessaround the catheter exit-site [7, 8, 9, 10].

Epidemiology

Healthcare institutions purchase millions of intravascularcatheters each year. The incidence of CRBSI variesconsiderably depending on the type of catheter (e.g.,tunneled versus non-tunneled), its site of insertion, theduration of placement, the frequency of catheter manip-ulation, and patient-related factors (i.e., the underlyingdisease and the acuity of the illness) [10]. The CDC andthe Joint Commission on Accreditation of HealthcareOrganizations (JCAHO) recommend that the rate ofCRBSI be expressed as the number of CRBSI per 1,000CVC days [11, 12]. This parameter is more useful than thenumber of catheter-associated infections per 100 catheters(or the percentage of catheters studied), because it ac-counts for CRBSI over time and therefore adjusts the riskfor the number of days the catheter is used.

Only a few studies have investigated the incidence ofCVC-related infections in children treated with HD, the

most important of which are the retrospective assessmentof Goldstein et al. [3] and the prospective analysis ofSharma et al. [13]. In the first study, the rates of infectionleading to the removal of uncuffed and cuffed catheterswere respectively 0.58 and 0.71 per patient-year [3]. Inthe second study, the 1-year survival of 36 cuffed CVCswas 62%, with six episodes of bacteremia being respon-sible for CVC removal [13].

However, CRBSI rates vary considerably, dependingon the size of the hospital and hospital service/unit [14].The documented overall CRBSI rate reported in the ma-jority of pediatric and adult studies was 1.2–1.6 episodes/1,000 catheter days [15, 16, 17, 18, 19, 20, 21]. Rates ofCRBSI in patients in pediatric intensive care units arehigher than those in patients in adult intensive care units[8].

Table 1 shows the etiology of CVC-related infectionsin three studies of children treated with HD [13, 15, 16].Coagulase-negative staphylococci and Staphylococcusaureus were the most frequent bacterial isolates, followedby enterococci, gram-negative pathogens, mycobacteria,and Candida spp. [13, 15, 16]. Interestingly, Hymes et al.[16] reported an outbreak of bacteremia secondary toEnterococcus fecalis in a pediatric hemodialysis unit inwhich no common source of Enterococcus could beidentified by cultures or serotyping.

One of the main concerns over the last 10 years hasbeen the increasing prevalence of antimicrobial-resistantmicro-organisms in dialysis facilities. In recent series,methicillin-resistant S. aureus (MRSA) was isolated in20%–40% of bacteremic episodes in HD patients andabout three-quarters of coagulase-negative staphylococcalisolates were methicillin resistant [22, 23]. The isolationof vancomycin-resistant staphylococci and enterococcisoared from 0.5% in 1989 to 25.9% in 1999 [11, 23], andthere has been a significant increase in the Enterobacte-riaceae that produce extended-spectrum b-lactamases,particularly Klebsiella pneumoniae [24]. Such organismsare not only resistant to cephalosporins, but also to fre-quently used, broad-spectrum antimicrobial agents. Otherepidemiological and clinical data document that in Can-dida spp. fluconazole resistance is becoming increasinglyrelevant when designing empiric therapeutic regimens forCRBSI [25].

Table 1 Etiology of central venous catheter-related infections in children treated with hemodialysis. Numbers are absolute values

Sharma et al. [13](exit site)

Sharma et al. [13](bacteremia)

Chawla and Nevins [15](bacteremia)

Hymes et al. [16](bacteremia)

Staphylococcus aureus 14 32 6 1Coagulase- negative staphylococci 25 11 7 -Gram-negative bacilli 6 3 2 1Enterococcus fecalis - - 1 5Mycobacterium fortuitum - - 2 -

Others 6 11 - 11 a

Total 51 57 18 18a In 8 cases, Enterococcus faecalis

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Pathogenesis and risk factors

The pathogenesis of CVC-related infections is often dueto extraluminal colonization of the catheter as a result ofthe migration of skin organisms [10]. Contamination ofthe catheter hub substantially contributes to the intralu-minal colonization of long-term catheters. Catheters mayoccasionally become hematogenously seeded from an-other focus of infection, whereas infusate contaminationonly rarely leads to CRBSI [10].

A number of predisposing risk factors have beenidentified. In general, infection rates are substantiallyhigher in the case of a failure to observe correct hygieneprocedures and aseptic techniques for CVC insertion andcare, a longer duration of catheterization, and a highfrequency of manipulation [4].

Another risk factor is represented by the type ofcatheter because infection rates are substantially lower inpatients with tunneled catheters [9]. Moreover, in vitrostudies have demonstrated that catheters made of poly-vinyl chloride or polyethylene are probably less resistantto the adherence of micro-organisms than those made ofTeflon, silicone elastomer, or polyurethane [26] andsome catheter materials also have surface irregularitiesthat enhance the microbial adherence of certain species(e.g., coagulase-negative staphylococci) [27]. However,although there are in vitro data on the role of cathetermaterials and bacterial adherence in causing CRBSI,there are few data suggesting that these factors make adifference in the clinical and in vivo setting.

Among the possible CVC insertion sites, the subcla-vian vein is associated with the lowest risk of infection[28]. However, since the use of a subclavian catheter isassociated with early subclavian venous stenosis, whichcompromises future arteriovenous creation in the ipsilat-eral arm, the right internal jugular vein should be con-sidered as first choice for vascular access [1, 29, 30].

Host factors such as immunosuppression, diabetesmellitus, hypoalbuminemia, and high ferritin levels haveall been associated with an increased risk of CRBSI [4,5]. Nasal and cutaneous colonization with S. aureus hasbeen reported as a risk factor for systemic infection, withpredictive values of 36% for positive nasal cultures and72% for positive cultures from the insertion site [4, 31,32].

The incidence of infection caused by the HD vascularaccess is highest when it is a CVC and lowest when it is anative artetriovenous fistula. Unfortunately, the prostheticarteriovenous graft (AVG) composed of polytetrafluoro-ethylene, which has become an acceptable alternative tothe native arteriovenous fistula, when the latter is notsurgically feasible, is very often plagued by infection [4,33, 34]. Occult infection of old non-functioning AVGs isa risk factor for bacteremia and serious AVG-related in-fection. Presenting symptoms considerably vary and insome patients no clinical signs of infection are detected.In such cases, an indium scan may show increased uptakecompatible with an infected AVG [33, 34].

As the number of lumina does not directly affect therate of CVC-related complications, the choice of a single-or multi-lumen catheter should be based on the type re-quired to deliver the needed medications or support [7].

Strategies aimed at preventing CVC-related infections

Continuous healthcare worker education and training

Over the last 20 years, there have been many reports in-dicating that the risk of infection declines after the stan-dardization of aseptic care, and that the insertion andmaintenance of CVCs by inexperienced staff can increasethe risk of catheter colonization and CRBSI [10, 35].Catheters should only be managed by trained staff, thelumen should never remain open to the air, and a surgicalmask should be worn by patients and nurses whenever thecatheter is accessed. It is mandatory that dialysis staffshould also wear sterile gloves when handling CVCs [1,9, 10, 35]. The use of chlorhexidine-based solutions maybe preferable to the use of povidone iodine solutions,because chlorhexidine reduces the risk of catheter colo-nization [36, 37].

Type of venous access

The use of HD catheters is the most common factorcontributing to bacteremia in dialysis patients [38, 39]. Ifa temporary access is needed, a non-cuffed or a cuffedpercutaneously inserted catheter should be used [1]. In thecase of chronic HD, tunneled CVCs should be consideredwhen an arteriovenous fistula is not feasible, with theTesio catheter system being adopted as an alternative tostandard catheters [1]. In children on chronic HD, Sheathet al. [39] reported the superiority of Tesio catheters (i.e.,twin single-lumen catheters of different lengths lying inparallel in a single vein) over double-lumen CVCs interms of catheter survival, infection rates, and the dura-tion of adequate performance. A totally implantable port-system (Dialock) has been recently developed as a dial-ysis access, which consists of a subcutaneously implantedmetallic chamber connected to permanent silicone twincatheters ending in the right atrium that is percutaneouslyaccessed at each dialysis session using special needlecannulas that convert it into a conventional twin-cathetersystem [4]. However, there are few data on the use of theDialock system either in terms of the rate of technicalcomplications or whether it will reduce the infection riskas one would expect.

Site of insertion

Although a subclavian site is preferred for infectioncontrol purposes, as previously suggested the other factorsthat should be considered include the potential for me-chanical complications, the risk of subclavian vein ste-

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nosis and the skill of the catheter-operator, as well asphysical comfort, the maintenance of asepsis, and patient-specific factors [10]. Interestingly, studies of pediatricpatients have shown that femoral catheters have a lowincidence of mechanical complications and may have aninfection rate that is equivalent to that of non-femoralcatheters [40, 41, 42].

Catheter site dressing regimen

Transparent, semi-permeable polyurethane dressings havebecome a popular means of dressing catheter insertionsites as they reliably secure the device, allow continuousvisual inspection, permit patients to bathe and showerwithout saturating the dressing, and require less frequentchanges than standard gauze and tape dressings. How-ever, as no randomized study has yet demonstrated anysignificant differences between the two types of dressings[7, 8], the choice can be a matter of preference, withgauze dressings perhaps being favored if blood is oozingfrom the insertion site.

Systemic antibiotic prophylaxis

Most studies of prophylactic oral or parenteral antibioticshave shown that they are associated with a reducedCRBSI rate [43, 44]. However, their use is discouragedbecause of concerns that they encourage the emergence ofantibiotic-resistant organisms [7, 8].

Antimicrobial-impregnated catheters

Catheters impregnated with chlorhexidine and silver sul-fadiazine or minocycline and rifampin are the most fre-quently used types of antimicrobial-impregnated catheters[7, 10]. Their use seems to lower the incidence of bothcatheter colonization and CRBSI in patients at high riskfor CVC-related infections [45, 46, 47, 48, 49] and de-crease direct medical costs [45]. However, as this findingcomes from a single randomized trial and the relative costeffectiveness of the two types of catheters has not yetbeen formally evaluated [47], either may be used.

Nevertheless, a review of 11 randomized trials aimedat assessing the efficacy of antimicrobial-impregnatedCVCs has revealed a number of methodological flaws,including inconsistent definitions of CRBSI, a failure toaccount for confounding variables, sub-optimal statisticaland epidemiological methods, and the rare use of clini-cally relevant end-points [49]. This means that more-rigorous studies on the possibility that the use of anti-microbial-impregnated catheters may lead to the emer-gence of resistant organisms are urgently required.

Antibiotic/antiseptic ointments

The DOQI guidelines of the National Kidney Foundationrecommend the application of povidone iodine or mu-pirocin ointment at the catheter exit site after CVCplacement and at the end of each dialysis session [1].However, the only currently available data are limited toadults. A randomized controlled trial of the application oftopical povidone iodine ointment to temporary catheterexit-sites in adult HD patients found that this approach iseffective in decreasing the incidence of exit-site infec-tions, catheter colonization, and sepsis, particularly innasal S. aureus carriers [46], but conflicting results havealso been reported [50, 51, 52, 53, 54, 55, 56, 57, 58].Furthermore, there have been isolated reports that mu-pirocin may adversely affect the integrity of polyurethanecatheters [59, 60].

In HD patients who were nasal carriers of S. aureus,the use of nasal mupirocin has been associated with afourfold reduction in the rate of CRBSI due to S. aureus[32], but resistance to mupirocin may develop in both S.aureus and coagulase-negative staphylococci soon afterthe start of its routine administration [10].

Antibiotic lock prophylaxis

The post-dialysis instillation of concentrated antibioticsolutions into the catheter lumen has been attempted as ameans of preventing CRBSI, but it is not currently rec-ommended because of the risk of selecting resistantstrains and the lack of data concerning children on HD [7,8, 9]. Rackoff et al. [61] found that the addition of van-comycin to heparin CVC flush solutions did not reducebacteremia from vancomycin-susceptible organisms in55 children with cancer and 8 on total parenteral nutri-tion, although Henrickson et al. [62] reported that theuse of vancomycin-heparin or vancomycin-heparin-ci-profloxacin flush solutions led to a significant decrease inthe complications associated with tunneled CVCs in 126pediatric oncology patients. It has also been reported thatthe use of solutions containing gentamycin/citrate [63] ortaurolidine/citrate [64] had a positive effect in adult HDpatients.

Anticoagulant solutions

Anticoagulant flush solutions are widely used to preventcatheter thrombosis. As thrombi and fibrin deposits oncatheters may act as a nidus for the microbial colonizationof CVCs, the use of anticoagulants may help to preventCRBSI [10]. A meta-analysis of 14 randomized controlledstudies concluded that the administration of heparin ef-fectively reduces thrombus formation and may decreasecatheter-related infections in patients with a CVC [65].However, as most heparin solutions contain preservativesthat have antimicrobial activity, it is not clear whether the

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decreased CRBSI rate is a result of reduced thrombusformation, the preservative, or both.

Scheduled catheter replacement

The scheduled replacement of CVCs has been proposedas a means of preventing phlebitis and catheter-relatedinfections [10]. However, a systematic review of the lit-erature found that routine CVC exchange does not reduceinfections in comparison with catheter replacement on anas-needed basis [66]. CVCs should therefore not be re-placed in a scheduled manner.

Treatment of catheter-related infections

The clinical presentations of CRBSI vary. An acute onsetof fever and chills in a patient with a HD catheter and nolocal signs is easily recognized and generally consideredto be a CRBSI until proven otherwise [4]. Less acutepresentations of CRBSI are also frequent, especially inimmunocompromised patients, and may include the in-sidious onset of low-grade fever, hypothermia, lethargy,confusion, hypotension, hypoglycemia, or diabetic keto-acidosis [4].

Once a catheter-related infection is suspected, twoblood samples should be taken for culture, at least one ofwhich should be drawn percutaneously [8]. A positiveculture of blood from a CVC may be associated with onlycatheter colonization and requires clinical interpretation,but a negative result can help to exclude CRBSI [7, 8].

Three points need to be discussed in detail concerningthe treatment of CVC-related infections: optimal antimi-crobial therapy, the need for catheter replacement, and theusefulness of antibiotic lock therapy.

Antimicrobial therapy

Antibiotic therapy for CVC-related infections is oftenstarted empirically, with the initial choice of antibioticsdepending on the severity of the patient’s clinical disease,the risk factors for infection, and the likely pathogensassociated with the specific intravascular device. Ac-cording to the majority of authors, exit-site infectionswithout systemic symptoms and with negative bloodcultures can be treated using topical antibiotics alone [4,8]. In contrast, tunnel infections and bacteremias requireparenteral antimicrobial therapy that also takes into ac-count the frequency of the bacterial isolates in such set-tings [4, 8]. Although there are no data supporting the useof specific empirical antibiotic therapy, vancomycin isusually recommended in hospitals or countries with anincreased incidence of methicillin-resistant staphylococcibecause of its activity against coagulase-negative sta-phylococci and S. aureus [8]. In the absence of MRSA, apenicillinase-resistant penicillin such as nafcillin or ox-acillin should be used [8]. Additional empirical coverage

for enteric gram-negative bacilli with a third-generationcephalosporin should be included to avoid unwarrantedrisks [8], and the use of amphotericin B, or, in selectedpatients, intravenous fluconazole should also be consid-ered when fungemia is suspected [8]. Specific antimi-crobial therapy should be adopted as soon as the identityof the bacterial isolate has been determined.

One matter of debate is the optimal duration of ther-apy, which clearly depends on the severity of the infectionand its etiological agent. The DOQI guidelines recom-mend a minimum of 3 weeks systemic antibiotic therapywhenever a CRBSI is proved [1], but in our opinion, andin accordance with the guidelines of the Infectious Dis-eases Society of America (IDSA), most patients shouldreceive 10–14 days of antimicrobial therapy [8]. Thetreatment should be continued for longer periods (14 daysafter the last positive blood culture) in the case of fungalinfections or evidence of endocarditis or septic throm-bosis (duration 4–6 weeks), and 6–8 weeks of therapyshould be considered for the treatment of osteomyelitis[8].

Catheter replacement

Once again, there is no clear consensus concerning thisaspect of treatment. The results of a number of studies ofchildren have suggested that some catheter-related in-fections may be cleared by antimicrobial therapy alone,and that the CVC need not be removed in up to 75% ofcases [67, 68, 69, 70, 71, 72, 73]. Furthermore, althoughthere have been anecdotal reports of the cure of fungemiawithout catheter removal, the treatment of CVC-associ-ated fungemia while retaining the catheter has a lowsuccess rate and may be associated with a higher mor-tality [8].

These findings underline the importance of carefullyselecting the patients for whom an attempt to salvagethe catheter could be considered. However, the cathetershould always be removed in the case of non-tunneledCVCs, unstable clinical conditions, bacteremia associatedwith exit-site infection, mycotic infections, and if feverpersists for more than 36 h after the start of antimicrobialtherapy [8]. Another option to consider is changing theCVC over a guidewire instead of removing it and re-placing it with a new CVC at a new site. In the absence ofexit-site infections, this approach seems to be safe andeffective in adult HD patients (even in the presence ofsepsis) as long as antibiotic therapy has been started [34,74, 75, 76, 77, 78, 79]; however, there are no data con-cerning children on HD.

Lock therapy

Often used together with systemic antibiotics, antibioticlock therapy involves instilling a high concentration of anantibiotic to which the causative microbe is susceptible inthe catheter lumen [8]. The volume of installed antibiotic

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is then removed before infusing the next dose of antibioticmedication or solution. Although the duration of antibi-otic lock therapy in different studies has varied, it hasmost often been 2 weeks [8]; the study with the lowestsalvage rate reported a mean of 8 days of therapy [8].

Two studies have observed favorable results using theantibiotic lock technique in pediatric patients. Johnson etal. [80] reported the successful treatment of 10 of 12episodes of persistent CVC infections by means of locksolutions specific for the isolated organism, and Cuntz etal. [81] observed only 1 failure and 2 recurrences whentreating 20 CVC-related infection episodes with a localteicoplanin lock for 15 days associated with double-an-tibiotic systemic treatment for 5 days. No studies ofchildren treated with HD have yet been performed.

As the purpose of antibiotic lock therapy is to sterilizethe catheter lumen, the patients should be selected on thebasis of a high likelihood of intraluminal infection and isnot feasible in the case of a suspected fungal infection anda high probability of extraluminal infection.

Practical approach to suspected CVC-related infections

On the basis of the available evidence, and taking intoaccount the published reviews and guidelines, we proposea practical algorithm for the management of catheter-re-lated infections in children treated with HD.

Non-tunneled catheters

Figure 1 shows a possible approach to suspected infec-tions related to percutaneously inserted CVCs. In the caseof an exit-site infection, the catheter should be removedand replaced at a new site. Topical antimicrobial therapyis recommended; systemic antibiotics should be addedonly in complicated cases and if a CRBSI is demon-strated. The systemic antibiotic therapy should be startedpromptly in the presence of signs of sepsis or septicshock. If the clinical presentation is severe or no source offever is identified, the catheter should be removed and itstip cultured. Exchange over a guidewire is a feasible

Fig. 1 Possible approach tosuspected infections in the caseof percutaneously inserted cen-tral venous catheters ( CVCs)

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option, even in the case of sepsis; however, if the tipculture is positive, the catheter should be removed andinserted at a new site and, in the case of a proven CRBSI,adequate antimicrobial therapy has to be started if this hasnot already been done.

Tunneled catheters

Figure 2 shows a possible approach to suspected infec-tions in HD children with tunneled CVCs. Exit-site in-fections should first be treated with topical antibioticswithout the removal of the CVC, with systemic antibiotictherapy and catheter replacement at a new site being in-dicated in complicated or unresponsive cases. However,tunnel infections always require systemic antibiotic ther-apy; also in this case, the catheter should be removed andreplaced only in the absence of a therapeutic response. If aCRBSI is suspected, empirical antibiotic therapy shouldbe started immediately after obtaining blood cultures, andthen modified as soon as the results of the cultures areavailable. In any clinically unstable patient, and in thepresence of exit-site or tunnel tract infections, the cathetershould be removed and the placement of a new permanentaccess should be postponed until the systemic antibioticcourse has been completed and a blood culture drawn atleast 48 h later yields negative results. Two strategies arefeasible in the case of uncomplicated bacteremia: the firstoption is to remove the catheter and delay its replacementat a new site or by means of a guidewire exchange; thesecond is to attempt antibiotic lock therapy for 14 dayswithout removing the catheter. CVC removal is manda-tory if the symptoms persist for more than 36 h after the

start of antimicrobial treatment, and in the case of clinicaldeterioration, or persistent or relapsing bacteremia. Fun-gal infections should prompt prolonged antimycotic ther-apy and catheter removal.

Conclusions

CVC-related infectious complications are a major sourceof morbidity among children treated with HD [4, 5, 6].Although several new strategies have been proposed in anattempt to reduce the risk of CVC-related infections, suchas catheters impregnated with antiseptics/antibiotics, lockantibiotic prophylaxis, nasal mupirocin, and the applica-tion of ointments at the exit site [7], their real efficacy stillhas to be demonstrated in the pediatric population. Themanagement of CVC-related infections is also still adifficult problem, mainly because a number of questionsare still under debate and there is a lack of studies of HDchildren. The unresolved issues include the choice ofoptimal antimicrobial therapy (because of the increasingisolation of multi-resistant bacterial strains) and its du-ration, whether the catheter has to be removed and thefeasibility of a guidewire exchange, and the usefulness ofantibiotic lock therapy. Only well-designed, prospectiveclinical trials specifically involving pediatric patients withESRD can contribute to clarifying optimal prevention andtreatment strategies for catheter-related infections in thispopulation.

Fig. 2 Possible approach tosuspected infections in childrenon hemodialysis with tunneledCVCs

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References

1. Work Group of the NFK-DOQI (2001) Clinical practiceguidelines for vascular access. Am J Kidney Dis 37 [Suppl 1]:S137–S181

2. Boudailliez B, Djeddi D, Lahoche A (2001) Central venousaccess for hemodialysis: use and practice with the child inFrance. Nephrologie 22:469–472

3. Goldstein SL, Macierowski CT, Jabs K (1997) Hemodialysiscatheter survival and complications in children and adolescents.Pediatr Nephrol 11:74–77

4. Nassar GM, Ayus JC (2001) Infectious complications of thehemodialysis access. Kidney Int 60:1–13

5. Fatkenheuer G, Cornely O, Seifert H (2002) Clinical manage-ment of catheter-related infections. Clin Microbiol Infect8:545–550

6. Blankestiin PJ (2001) Treatment and prevention of catheter-related infections in haemodialysis patients. Nephrol DialTransplant 16:1975–1978

7. McGee DC, Gould MK (2003) Preventing complications ofcentral venous catheterization. N Engl J Med 348:1123–1133

8. Mermel LA, Farr BM, Sherertz RJ, Raad II, O’Grady N, HarrisJS, Craven DE (2001) Guidelines for the management of in-travascular catheter-related infections. Clin Infect Dis 32:1249–1272

9. O’Grady NP, Alexander M, Dellinger EP, Gerberding JL,Heard SO, Maki DG, Masur H, McCormick RD, Mermel LA,Pearson ML, Raad II, Randolph A, Weinstein RA (2002)Guidelines for the prevention of intravascular catheter-relatedinfections. Pediatrics 110:e51

10. O’Grady NP, Alexander M, Dellinger EP, Gerberding JL,Heard SO, Maki DG, Masur H, McCormick RD, Mermel LA,Pearson ML, Raad II, Randolph A, Weinstein RA (2002)Guidelines for the prevention of intravascular catheter-relatedinfections. Clin Infect Dis 35:1281–1307

11. CDC (1999) National Nosocomial Infections Surveillance(NNIS) System report, data summary from January 1990-May1999, issued June 1999. Am J Infect Control 27:520–532

12. Joint Commission on the Accreditation of Healthcare Organi-zations (1994) Accreditation manual for hospitals. Joint Com-mission on the Accreditation of Healthcare Organizations,Chicago, pp 121–140

13. Sharma A, Zilleruelo G, Abitbol C, Montane B, Strauss J(1999) Survival and complications of cuffed catheters in chil-dren on chronic hemodialysis. Pediatr Nephrol 13:245–248

14. Tokars JI, Light P, Anderson J, Miller ER, Parrish J, ArmisteadN, Jarvis WR, Gehr T (2001) A prospective study of vascularaccess infections at seven outpatient hemodialysis centers. AmJ Kidney Dis 37:1232–1240

15. Chawla PG, Nevins TE (2000) Management of hemodialy-sis catheter-related bacteremia—a 10-year experience. PediatrNephrol 14:198–202

16. Hymes LC, Warshaw BL, Clowers B, Newsome P, KeyserlingHL (1996) Bacteremia in a pediatric hemodialysis unit sec-ondary to Enterococcus fecalis. Pediatr Nephrol 10:55–57

17. Mahan JD Jr, Mauer SM, Nevins TE (1983) The Hickmancatheter: a new hemodialysis access device for infants andsmall children. Kidney Int 24:694–697

18. Lally KP, Brennan LP, Sherman NJ, Grushkin C, Lieberman E,Atkinson JB (1987) Use of subclavian venous catheter forshort- and long-term hemodialysis in children. J Pediatr Surg22:603–605

19. Rovner MS, Brouhard BH, Cunningham RJ, Firor H (1992)Comparison of cuffed vs noncuffed catheters for extracorporealtherapy in pediatric patients. Dial Transplant 21:513–522

20. Vathada M, Neiberger RE, Pena DR, Fennel RS, Richard GA(1994) Complications of hemodialysis catheters in children.Dial Transplant 23:240–247

21. Bunchman TE (1996) Pediatric hemodialysis: lessons from thepast, ideas for the future. Kidney Int 53 [Suppl]:S64–S67

22. Berns JS (2003) Infection with antimicrobial-resistant micro-organism in dialysis patients. Semin Dial 16:30–37

23. Von Baum H, Schehl J, Geiss HK, Schaefer F (1999) Preva-lence of vancomycin-resistant enterococci among children withend-stage renal failure. Mid-European Pediatric PeritonealDialysis Study Group. Clin Infect Dis 29:912–916

24. Fridkin SK, Gaynes RP (1999) Antimicrobial resistance in in-tensive care units. Clin Chest Med 20:303–316

25. Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP(1998) National surveillance of nosocomial blood stream in-fection due to Candida albicans: frequency of occurrenceand antifungal susceptibility in the SCOPE Program. DiagnMicrobiol Infect Dis 31:327–332

26. Ashkenazi S, Weiss E, Drucker MM, Bodey GP (1986) Bac-terial adherence to intravenous catheters and needles and itsinfluence by cannula type and bacterial surface hydrophobicity.J Lab Clin Med 107:136–140

27. Nachnani GH, Lessin LS, Motomiya T, Jensen WN, Bodey GP(1972) Scanning electron microscopy of thrombogenesis onvascular catheter surfaces. N Engl J Med 286:139–140

28. Merrer J, De Jonghe B, Golliot F, Lefrant JY, Raffy B, Barre E,Rigaud JP, Caciani D, Misset B, Bosquet C, Outin H, Brun-Buisson C, Nitenberg G, French Catheter Study Group in In-tensive care (2001) Complications of femoral and subclavianvenous catheterization in critically ill patients: a randomizedcontrolled trial. JAMA 286:700–707

29. Shillinger F, Shillinger D, Montagnac R, Milcent T (1991) Postcatheterization venous stenosis in haemodialysis. Nephrol DialTransplant 6:722–724

30. Cimochowski GE, Worley E, Rutherford WE, Sartain J,Blondin J, Harter H. (1990) Superiority of internal jugular oversubclavian access for temporary dialysis. Nephron 54:154–161

31. Von Eiff C, Becker K, Machka K, Stammer H, Peters G (2001)Nasal carriage as a source of bacteremia. Study Group. N EnglJ Med 344:11–16

32. Boelart JR, Van Landuyt HW, Godard CA, Daneels RF,Schurgers ML, Matthys EG, De Baere YA, Gheyle DW, GordtsBZ, Herwaldt LA (1993) Nasal mupirocin ointment decreasesthe incidence of Staphylococcus aureus bacteremias in hemo-dialysis patients. Nephrol Dial Transplant 8:235–239

33. Nassar GM, Ayus JC (2002) Infectious complications of oldnonfunctioning arteriovenous grafts in renal transplant recipi-ents: a case series. Am J Kidney Dis 40:832–836

34. Nassar GM, Fishbane S, Ayus JC (2002) Occult infection of oldnonfunctioning arteriovenous grafts: a novel cause of erythro-poietin resistance and chronic inflammation in hemodialysispatients. Kidney Int [Suppl] 80:49–54

35. Sherertz RJ, Ely EW, Westbrook DM, Gledhill KS, Streed SA,Kiger B, Flynn L, Hayes S, Strong S, Cruz J, Bowton DL,Hulgan T, Haponik EF (2000) Education of physicians-in-training can decrease the risk for vascular catheter infection.Ann Intern Med 132:641–648

36. Maki DG, Ringer M, Alvarado CJ (1991) Prospective ran-domised trial of povidone-iodine, alcohol, and chlorhexidinefor prevention of infection associated with central venous andarterial catheters. Lancet 338:339–343

37. Mimoz O, Pieroni L, Lawrence C, Edouard A, Costa Y, SamiiK, Brun-Buisson C (1996) Prospective, randomized trial of twoantiseptic solutions for prevention of central venous or arterialcatheter colonization and infection in intensive care unit pa-tients. Crit Care Med 24:1818–1823

38. Oliver MJ, Callery SM, Thorpe KE, Schwab SJ, Churchill DN(2000) Risk of bacteremia from temporary hemodialysis ca-theters by site of insertion and duration of use: a prospectivestudy. Kidney Int 58:2543–2545

39. Sheath RD, Kale AS, Brewer ED, Brandt ML, Nuchtern JG,Goldstein SL (2001) Successful use of Tesio catheters in pe-diatric patients receiving chronic hemodialysis. Am J KidneyDis 38:553–559

40. Venkataraman ST, Thompson AE, Orr RA (1997) Femoralvascular catheterization in critically ill infants and children.Clin Pediatr (Phila) 36:311–319

1331

41. Goldstein AM, Weber JM, Sheridan RL (1997) Femoral venousaccess is safe in burned children: an analysis of 224 catheters.J Pediatr 130:442–446

42. Brittinger WD, Walker G, Twittenhoff WD, Konrad N (1997)Vascular access for hemodialysis in children. Pediatr Nephrol11:87–95

43. Kacica MA, Horgan MJ, Ochoa L, Sandler R, Lepow ML,Venezia RA (1994) Prevention of gram-positive sepsis inneonates weighing less than 1500 g. J Pediatr 125:253–258

44. Spafford PS, Sinkin RA, Cox C, Reubens L, Powell KR (1994)Prevention of central venous catheter-related coagulase-nega-tive staphylococcal sepsis in neonates. J Pediatr 125:259–263

45. Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD (1999)Efficacy of antiseptic-impregnated venous catheters in pre-venting catheter-related bloodstream infection: a meta-analysis.JAMA 281:261–267

46. Veenstra DL, Saint S, Sullivan SD (1999) Cost-effectiveness ofantiseptic-impregnated venous catheters for the prevention ofcatheter-related bloodstream infection. JAMA 282:554–560

47. Darouiche RO, Raad II, Heard SO, Thornby JI, Wenker OC,Gabrielli A, Berg J, Khardori N, Hanna H, Hachem R, HarrisRL, Mayhall G (1999) A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. NEngl J Med 340:1–8

48. Marciante KD, Veenstra DL, Lipsky BA, Saint S (2003) Whichantimicrobial impregnated central venous catheter should weuse? Modeling the costs and outcomes of antimicrobial catheteruse. Am J Infect Control 31:1–8

49. McConnell SA, Gubbins PO, Anaissie EJ (2003) Do antimi-crobial-impregnated central venous catheters prevent catheter-related bloodstream infections? Clin Infect Dis 37:65–72

50. Levin A, Mason AJ, Jindal KK, Foing IW, Goldstein MB(1991) Prevention of hemodialysis subclavian vein catheterinfections by topical povidone-iodine. Kidney Int 40:934–938

51. Sesso R, Barbosa D, Leme IL, Sader H, Caziana M, ManfrediS, Draibe S, Pignatari AC (1998) Staphylococcus aureus pro-phylaxis in hemodialysis patients using central venous catheter:effect of mupirocin ointment. J Am Soc Nephrol 9:1085–1092

52. Johnson DW, MacGinley R, Kay TD, Hawley CM, CampbellSB, Isbel NM, Hollett P (2002) A randomized controlled trial oftopical exit site mupirocin application in patients with tun-nelled, cuffed haemodialysis catheters. Nephrol Dial Transplant17:1802–1807

53. Silverberg D, Stozenko F, Blum M, Ben Tzion S, Schwartz D,Yachnin T, Baruch R, Shaked M, Iaina A, Siegman-Igra Y(2003) Mupirocin ointment application at the exit site of tem-porary central line hemodialysis catheters markedly reduces S.aureus bloodstream infections. Dial Transplant 32:484–489

54. Lok CE, Stanley KE, Hux JE, Richardson R, Tobe SW, Conly J(2003) Hemodialysis infections prevention with polysporinointment. J Am Soc Nephrol 14:169–179

55. Zakrzewska-Bode A, Muytjens HL, Liem KD, Hoogkamp-Korstanje JA (1995) Mupirocin resistance in coagulase-nega-tive staphylococci, after topical prophylaxis for the reduction ofcolonization of central venous catheters. J Hosp Infect 31:189–193

56. Perez-Fontan M, Rosales M, Rodriguez-Carmona A, Garcia-Falcon T, Valdez F (2002) Mupirocin resistance after long-termuse for Staphylococcus aureus colonization in patients under-going chronic peritoneal dialysis. Am J Kidney Dis 39:337–341

57. Annigeri R, Conly J, Vas S, Dedier H, Prakashan KP, BargmanJM, Jassal V, Oreopulos D (2001) Emergence of mupirocin-resistant Staphylococcus aureus in chronic peritoneal dialysispatients using mupirocin prophylaxis to prevent exit-site in-fection. Perit Dial Int 21:554–559

58. Flowers RH 3rd, Schwenzer KJ, Kopel RF, Fisch MJ, TuckerSI, Farr BM (1989) Efficacy of an attachable subcutaneous cufffor the prevention of intravascular catheter-related infection. Arandomized, controlled trial. JAMA 261:878–883

59. Rao SP, Oreopoulos DG (1997) Unusual complications of apolyurethane PD catheter. Perit Dial Int 17:410–412

60. Riu S, Ruiz CG, Martinez-Vera A, Peralta C, Oliver JA (1998)Spontaneous rupture of polyurethane peritoneal catheter. Apossible deleterious effect of mupirocin ointment. Nephrol DialTransplant 13:1870–1871

61. Rackoff WR, Weiman M, Jacobowski D, Hirschl R, StallingsV, Bilodeau J, Danz P, Bell L, Lange B (1995) A randomized,controlled trial of the efficacy of a heparin and vancomycinsolution in preventing central venous catheter infections inchildren. J Pediatr 127:147–151

62. Henrickson KJ, Axtell RA, Hoover SM, Kuhn SM, Pritchett J,Kehl SC, Klein JP (2000) Prevention of central venous cathe-ter-related infections and thrombotic events in immunocom-promised children by the use of vancomycin/ciprofloxacin/heparin flush solution: a randomized, multicenter, double-blindtrial. J Clin Oncol 18:1269–1278

63. Dogra GK, Herson H, Hutchinson B, Irish AB, Heath CH,Golledge C, Luxton G, Moody H (2002) Prevention of tun-nelled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: a randomizedcontrolled study. J Am Soc Nephrol 13:2133–2139

64. Allon M (2003) Prophylaxis against dialysis catheter-relatedbacteremia with a novel antimicrobial lock solution. Clin InfectDis 36:1539–1544

65. Randolph AG, Cook DJ, Gonzales CA, Andrew M (1998)Benefit of heparin in central venous and pulmonary artery ca-theters: a meta-analysis of randomized controlled trials. Chest113:165–171

66. Cook D, Randolph A, Kernerman P, Cupido C, King D, SoukupC, Brun-Buisson C (1997) Central venous catheter replacementstrategies: a systematic review of the literature. Crit Care Med25:1417–1424

67. Flynn PM, Shenep JL, Stokes DC, Barrett FF (1987) In situmanagement of confirmed central venous catheter-related bac-teremia. Pediatr Infect Dis J 6:729–734

68. Rubin LG, Shih S, Shende A, Karayalcin G, Lanzkowsky P(1999) Cure of implantable venous port-associated bloodstreaminfections in pediatric haematology-oncology patients withoutcatheter removal. Clin Infect Dis 29:102–105

69. Salzman MB, Rubin LG (1995) Intravenous catheter-relatedinfections. Adv Pediatr Infect Dis 10:337–368

70. Hiemenz J, Skelton J, Pizzo PA (1986) Perspective on themanagement of catheter-related infections in cancer patients.Pediatr Infect Dis 5:6–11

71. Prince A, Heller B, Levy J (1986) Management of fever inpatients with central vein catheters. Pediatr Infect Dis 5:20–24

72. Decker MD, Edwards KM (1988) Central venous catheter in-fections. Pediatr Clin North Am 35:579–612

73. Hartman GE, Shochat SJ (1987) Management of septic com-plications associated with Silastic catheters in childhood ma-lignancy. Pediatr Infect Dis J 6:1042–1047

74. Shaffer D (1995) Catheter-related sepsis complicating long-term, tunnelled central venous dialysis catheters: managementby guidewire exchange. Am J Kidney Dis 25:593–596

75. Robinson D, Suhocki P, Schwab SJ (1998) Treatment of in-fected tunneled venous access hemodialysis catheters withguidewire exchange. Kidney Int 53:1792–1794

76. Tanriover B, Carlton D, Saddekni S, Hamrick K, Oser R,Westfall AO, Allon M (2000) Bacteremia associated withtunnelled dialysis catheters: comparison of two treatment stra-tegies. Kidney Int 57:2151–2155

77. Beathard GA (1999) Management of bacteremia associatedwith tunnelled-cuffed hemodialysis catheters. J Am Soc Ne-phrol 10:1045–1049

78. Martinez E, Mensa J, Rovira M, Martinez JA, Marcos A,Almela M, Carreras E (1999) Central venous catheter exchangeby guidewire for treatment of catheter-related bacteraemia inpatients undergoing BMT or intensive chemotherapy. BoneMarrow Transplant 23:41–44

79. Michel LA, Bradpiece HA, Randour P, Pouthier F (1988)Safety of central venous catheter change over guidewire for

1332

suspected catheter-related sepsis. A prospective randomizedtrial. Int Surg 73:180–186

80. Johnson DC, Johnson FL, Goldman S (1994) Preliminary re-sults treating persistent central venous catheter infections withthe antibiotic lock technique in pediatric patients. Pediatr InfectDis J 13:930–931

81. Cuntz D, Michaud L, Guimber D, Husson MO, Gottrand F,Turck D (2002) Local antibiotic lock for the treatment of in-fections related to central catheters in parenteral nutrition inchildren. J Parenter Enteral Nutr 26:104–108

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