Hemodialysis Infection Prevention with Polysporin Ointment
Charmaine E. Lok*,,
Kenneth E. Stanley,
Janet E. Hux*,
Robert Richardson*,
Sheldon W. Tobe* and
John Conly*
*University of Toronto, Toronto, Canada; and Harvard School of Public Health, Boston, Massachusetts.
Correspondence to Dr, Charmaine E. Lok, Department of Medicine, Division of Nephrology, The Toronto General Hospital, 11 EN-216, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. Phone: 416-340-4140; Fax: 416-586-9827;
ABSTRACT. Hemodialysis patients in whom permanent vascular accesscannot be achieved are dependent on a central venous catheter.In such patients, catheter-related infections are a common andserious complication. This study was a randomized clinical trialto determine if topical Polysporin Triple antibiotic ointmentapplied to the central venous catheter insertion site couldreduce the incidence of catheter-related infections. A totalof 169 patients receiving hemodialysis through a central venouscatheter were randomized to receive Polysporin Triple or placebousing a double-blind study design. In the 6-mo study period,infections were observed in more patients in the placebo groupthan in the Polysporin Triple group (34 versus 12%; relativerisk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The number ofinfections per 1000 catheter days (4.10 versus 1.02; P <0.0001) and the number of bacteremias per 1000 catheter days(2.48 versus 0.63; P = 0.0004) were also greater in the placebogroup. Within the 6-mo study period, there were 13 deaths inthe placebo group as compared with 3 deaths in the PolysporinTriple group (P = 0.0041). When all available follow-up informationwas included, the difference in survival remained significant(19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infectionswere observed in 7 of the 13 placebo subjects who died (54%)as compared with no infections in the three Polysporin Triplesubjects who died. The prophylactic application of topical PolysporinTriple antibiotic ointment to the central venous catheter insertionsite reduced the rate of infections and was associated withimproved survival in hemodialysis patients. E-mail: charmaine.lok@uhn.on.ca
Infection is the most common cause of morbidity and the secondmost common cause of death in hemodialysis (HD) patients (1–5).Bacteremia accounts for more than 75% of these infectious deaths(4). Hemodialysis vascular access is implicated as the sourceof bacteremias in 48 to 73% (3,6–7) of cases with patientsdependent on central venous catheters (CVC) being at highestrisk (2,7–9). Currently, approximately 20% of patientsare dialyzed using permanent catheters; both their placementrate and length of use has increased (1,4). Staphylococcus aureushas previously been the primary etiologic agent implicated incausing approximately half of the bacteremic episodes (7,10)and 70% of the vascular access site infections (11–12).However, recent studies have reported a greater percentage andvariety of Gram-negative bacteria isolated in catheter-relatedinfections (13–16). Polysporin Triple (PT) is an antibioticointment composed of 500 U/g bacitracin, 0.25 mg/g gramicidin,and 10,000 U/g polymyxin B and is active topically against mostskin flora (e.g., S. aureus, coagulase negative staphylococcus,and most Gram-negative bacteria). Previous studies have demonstratedsuccess in preventing catheter-related infections using topicalpovidone-iodine (17) or mupirocin (12,18,19), antibiotic orsilver-coated catheters (20–22), and other novel methods(23–25). However, the optimal strategy for long-term infectionprophylaxis for tunneled permanent catheters has not been establishedin the current environment of changing microbes and clinicalpractice. The objective of this study was to determine if topicalPT ointment applied at the catheter exit site could reduce theincidence of hemodialysis catheter-related infections over a6-mo period.
Study Design
This multicenter study was a double-blind, placebo-controlled,randomized clinical trial. The patients, clinicians, microbiologists,pharmacist, and data managers were unaware of the treatmentallocation. Patients were stratified into two groups beforerandomization on the basis of the time interval between CVCinsertion and study enrollment (7 d was called "incident catheter,"and others were called "prevalent catheter"). Patient randomizationwas performed at an independent central randomization facilityvia a computer-generated random number list, using blocked randomizationwith a block size of 4. Written informed consent was obtainedfrom all patients or their legal representative. The study protocolwas approved by the Research Ethics Boards of the participatingCanadian institutions and the funding agency. The use of a placeboointment on a chlorhexidine-cleansed site was justified at thetime, as the study was designed and approved before the CanadianSociety of Nephrology guidelines for vascular access (26) werepublished.
Study Population
The study population consisted of consecutive individuals withend-stage renal disease (ESRD) who required hemodialysis andused a permanent tunneled cuffed catheter in the internal jugularvein as their vascular access for dialysis. All such patientswho met the inclusion criteria were approached to enter thestudy. The inclusion criteria were age greater than 18 yr anda need for a cuffed catheter as the primary source of vascularaccess for one of the following reasons: ESRD without permanentvascular access, recent conversion from peritoneal dialysisto HD, or recent loss of an arteriovenous fistula or graft.Exclusion criteria were as follow: acute renal failure, antibioticuse by any route in the week before enrolling in the study,known allergy to any component of PT, use of a temporary HDcatheter (non-cuffed), use of the CVC for purposes other thanaccess for HD, e.g., chemotherapy or TPN, active malignancy,or involvement in another drug trial.
Study Treatment and Outcomes
A placebo ointment was prepared that matched the PT ointmentwith respect to appearance and consistency. The study ointment(treatment or matched placebo) was contained in brown opaque50-g glass jars marked only with the patient’s name andstudy number to ensure masking of the study from trained hemodialysisnurses who applied the ointment. After enrollment, the studyointment was applied at the end of each dialysis session for2 consecutive weeks (6 sessions) and then with the patient’sweekly dressing change and when dressing changes were clinicallyindicated. A high compliance with ointment application was assuredby obtaining input from the HD nurses during the study designphase and random checks comparing the amount of ointment usedfor patients enrolled at similar times.
The study dressing protocol was standardized to reflect thecurrent practice of the two institutions and included cleansingaround the exit site with a Chlorhexidine gluconate (0.5% in70% alcohol) applicator, a 1-cm cotton swab application of studyointment to the CVC exit site, and then application of a 2 x2 in. dry gauze dressing secured with a porous, nontransparentadhesive (hypafix). To avoid erosion and to ensure compatibilitywith the chlorhexidine and PT, the catheters used were not glycolbased. All catheters (Uldall Cook, Cook Canada Inc.) and Cardiomed(Cardiomed Supplies Inc.) were placed by interventional radiologistsusing aseptic techniques (sterile gowns, gloves, mask, cap,drape). Suspected cases of infection were identified by trainedHD nurses who would then notify the attending physician to examinethe patient. The findings were documented by the nurse on aquestionnaire and submitted to the primary investigator forreview, confirmation, and classification. The primary endpointwas the proportion of patients with a catheter-related infectionwithin 6 mo after entry into the study. These infections included:(1) exit site infection (ESI); (2) tunnel infections; and (3)bacteremia. This endpoint was evaluated in a blinded fashionby the primary investigator (CL) according to the Canadian definitionsfor catheter-related infections (27). Cases with "definite"and "probable" infections (Table 1) were classified as infections,as was agreed before the commencement of the study.
Table 1. Definitions of catheter-related infections
All catheter-related infections were treated by the patient’sattending staff nephrologist according to their usual practice.If a new catheter was clinically indicated, the patient continuedto receive the same ointment to which they had been assigned.Swabs for cultures and sensitivities at the catheter exit sitewere taken if an exit or tunnel infection was suspected andblood cultures if a bacteremia was suspected. Surveillance nasaland catheter exit site swabs were obtained at the time of patientenrollment and every 3 mo for the duration of the study. Site-specificlaboratories were used for microbiologic identification of organismsusing standard methods (28). The study ended when the last enrolledsubject completed the minimum 6-mo study period.
Statistical Analyses
A minimum of 36 patients in each treatment group was requiredto detect a 50% difference between the treatment and placebogroups with respect to infections per patient with 80% powerusing a two-sided test with an of 0.05 (based on the previousyear’s average of 0.7 infections/patient per yr betweenthe two institutions). The follow-up period for the primaryendpoint was defined from the beginning of the study to be 6mo. A follow-up period of 12 mo was considered too long forreliable results, because beyond 6 mo the rate of infectionappears to decline, the need for secondary catheters rises,and there is substantially greater risk that confounding factorscould cloud the study results. We assessed differences in proportionsusing Fisher’s exact test and the number of infectionsper 1000 catheter-days using the exact binomial test (29). Time-to-eventdistributions were estimated using the Kaplan-Meier method andcompared using the log-rank test (30). The relative risk reductionand number of patients needed to treat (NNT) to prevent oneinfection, bacteremia, and death were determined (31). Analyseswere based on an intention-to-treat approach, except for theexclusion of seven blinded subjects who never started treatment.Analyses were performed using SAS, version 8.e (SAS Institute,Cary, NC).
Of 172 patients approached to participate in this clinical trial,169 (98%) consented and entered the study between November 1999and November 2000 (154 patients from the University Health Network-TorontoGeneral Hospital and 15 from Sunnybrook and Women’s CollegeHealth Sciences Center). Of the 169 patients randomized, studytreatment (blinded PT or placebo ointment) was not initiatedfor seven patients. The reasons for patients not beginning assignedtreatment were recovery of kidney function not requiring dialysis(two cases, one in each group), changed mind shortly after randomization(one case assigned to placebo), renal transplant (one case assignedto PT), and requiring long-term antibiotics for non–dialysis-relatedmedical reasons (three cases, one assigned to PT). Of thesecases, two from each group did not yet have their catheter insertedat the time of withdrawal. These seven blinded patients whodid not initiate protocol treatment were excluded from the analyses;however, in sensitivity analyses including these 7 patients,the results remain unchanged. Analysis and results of the remaining162 patients are reported here. Overall, 94 (58%) of the patientsremained in the study for at least 6 mo: 44% of the placebogroup, and 71% of the PT group. The most common reasons forless than 6 mo of follow-up were a mature, usable permanentaccess (15% of the 162 cases), death (10%), and transfer toa nonstudy dialysis unit (7%). Any infectious complicationsthat resulted in less than 6 mo follow-up were related to deathsas noted in a later section of this paper. No patients werelost to follow-up (Figure 1).
Figure 1. Flow and status of patients. *Other: recovery of renal function (two in each group), skin sensitivity to ointment (one in each group), developed active malignancy and use of long-term antibiotics (one in placebo), kidney transplant (one in placebo), required long-term antibiotics for active skin disorder (one in PT group) and for leg amputation (one in PT group), and began using novel access (one in placebo).
Table 2 gives the baseline patient characteristics by treatmentgroup. Rates of infection were not statistically different bybaseline characteristics (Table 3).
Table 3. Rate of infection by patient baseline characteristics
Infections
A higher proportion of patients experienced an infection inthe placebo group as compared with the PT group (34% versus12%; P = 0.0013; Table 4). This represented a 65% relative riskreduction (relative risk, 0.35; 95% CI, 0.18 to 0.68); the NNTwith PT to prevent one infection was 5 (95% CI, 3 to 11). Sixteenof the 27 patients with an infection in the placebo group and8 of the 10 patients with infections in the PT group experiencedonly a single infection. In the placebo group, the number ofinfections per 1000 catheter-days was greater (4.10 versus 1.02;P < 0.0001) and the time to first infection was shorter (P= 0.0002, log-rank test; Figure 2). The above-mentioned treatmentcomparisons were also consistently significant when all availablefollow-up was used for the analysis.
Figure 2. Percentage of patients with an infection.
Of the 43 infections in the placebo group, 26 were bacteremiaand 17 were exit site infections. Fourteen (54%) of bacteremiasand 14 (82%) of the ESI were defined as "definite" in this group.Of the 13 infections in the PT group, eight were bacteremiaand five were ESI. Three (38%) of bacteremias and four (80%)of ESI were defined as "definite" in the PT group. The majorityof infections (54%) were caused by coagulase-negative staphylococci,and S. aureus accounted for 18% of infections (Table 5).
Bacteremias
The proportion of patients who experienced a bacteremia wassignificantly higher in the placebo group than in the PT group(24% versus 10%; P = 0.020; Table 3). This represented a 60%relative risk reduction (relative risk, 0.40; 95% CI, 0.19 to0.86) and a NNT of 7 (95% CI, 4 to 33). The rate of bacteremiaswas 2.48 per 1000 catheter-days in the placebo group as comparedwith 0.63 in the PT group (P = 0.0004). The time to first bacteremiawas significantly shorter in the placebo group (P = 0.0056,log-rank test; Figure 3).
Mortality
There were 13 deaths in the placebo group as compared with 3deaths in the PT group within the 6-mo study period (P = 0.0041,log-rank test; Figure 4). This represented a 78% relative riskreduction and a NNT of 8 (95% CI, 5 to 27). No infections wereobserved in the three patients who died in the PT group (Table 6).In contrast, 7 (54%) of the 13 patients in the placebo groupwho died within the first 6 mo had infections before death.Of those with a preceding infection, all were hospitalized and100% had bacteremias in the placebo group versus no hospitalizationsand no bacteremias in the treatment group. When all availablefollow-up information was used, the survival advantage demonstratedby the PT group persisted (19 deaths in the placebo group and9 in the PT group; P = 0.0027, log-rank test).
Table 6. Causes of death, infections, and organisms for patients who died within 6 mo
Morbidity Related to Infections
More patients in the placebo group than in the PT group requiredhospitalization (24% versus 7%; P = 0.0041) and required catheterremoval due to infections (27% versus 10%; P = 0.0071; Table 4).
Prevalence of S. aureus Nasal and Exit Site Carriage
Fifteen percent of patients in the placebo group and 13% ofpatients in the PT group had S. aureus nasal carriage at baseline.The prevalence remained stable over time and similar betweenthe two treatment groups (data not shown). Five percent of patientsin the placebo group and 4% of patients in the PT had S. aureuscolonized at the catheter exit site at baseline. The catheterprevalence dropped markedly in the first few months for bothgroups. Within the first 6 mo, there was a consistent 22 to25% colonization of non–S. aureus organisms at the exitsite in the placebo-treated group compared with 10 to 11% inthe PT group.
Worldwide, increasing numbers of people are reaching ESRD andrequiring renal replacement therapy. In the United States, thereare more than 215,000 people who require hemodialysis (4). Oncedialysis is required, a safe and reliable means of vascularaccess is essential; central venous catheterization providesrapid access and is an accepted procedure while patients awaitmore definitive access (1,4,32). However, this approach is associatedwith infection risks (9,33,34). For example, catheter exit siteinfections are commonly associated with bacteremias (8 to 21%of cases) and are important causes of catheter loss (8,13).Bacteremias and tunnel infections are not only the leading causeof catheter loss, but they are associated with recurrence ofinfection, serious metastatic complications, and death (2,6–9,32).
Previous studies have evaluated prophylactic therapies to reducecatheter-related infections. Many have demonstrated importantreductions in S. aureus skin colonization, exit site infections,and bacteremias using various agents. Current guidelines (26,35)for the use of povidone-iodine in the prevention of HD catheter-relatedinfections are based primarily on the study by Levin et al.(17). They evaluated 10% povidone-iodine ointment applied togauze adjacent to the skin entry site compared with gauze alonein a randomized trial of 129 patients. All patients had singlelumen nontunelled subclavian catheters and had their skin andcatheter hub prepped with povidone-iodine solution at each dressingchange (3 times per wk). They found a septicemia rate of 1/63in the treated group versus 11/66 in the control group and significantreductions in exit site infections and catheter tip colonization.The mean catheter duration was 38.6 d in the treatment groupand 36.2 d in the control group. Other studies have demonstrateda reduction in infection rates when topical mupirocin has beenapplied to the catheter exit site (19) and nares (11,12,18).For example, Sesso et al. found a marked increase in S. aureusbacteremia when mupirocin was not used (hazard ratio of 7.2)in their trial of mupirocin versus povidone-iodine applied tothe exit site of temporary catheters. However, the results ofthese studies are difficult to generalize because they examinedprimarily non-cuffed, temporary catheters at subclavian sites,which carry a different risk of infection (8,36–38) andare not recommended in current guidelines (26,35). Thus, currentguidelines are imperfect in that they advocate tunneled cuffedvenous catheters inserted at the internal jugular vein as themethod of choice for permanent catheter use (>3 wk duration)(35) but recommend an agent (povidone-iodine) for infectionprophylaxis that is unproven in that situation. For this andother reasons, this study was ethically justified. In addition,the value of previously studied single-drug antibiotic prophylaxisis limited by the increasing prevalence of resistance to agentssuch as mupirocin (39–41). Other studies that have demonstrateda reduced rate of skin colonization and bacteremias includethose involving catheters coated with chorhexidine-silver sulfadiazine(21,22,42,43) or minocycline and rifampin (20). These studiesare limited by their short-term catheterization and efficacy(42), reduced antimicrobial activity over time (43,44), potentialfor microbial resistance (45), and generalizability to the chronichemodialysis population.
The key strengths of our study are the long duration of follow-up,use of guideline-recommended cuffed, tunneled catheters at theinternal jugular site, and evaluation of a simple, low cost,prophylactic agent less susceptible to microbial resistancein a placebo-controlled design. Our study patients appear representativeof the general dialysis population (Table 2). Furthermore, inthe placebo group, the rate of bacteremia was similar to ourbaseline rate (2.7/1000 catheter-days in the year before thestudy) and the overall rate of infection (4.1/1000 catheter-days)was consistent with our two institutions’ pretrial infectionrate and with that reported in the literature (8,13–15).
This is the first study of prophylactic topical therapy in theprevention of permanent HD catheter-related infections thatappears to have demonstrated an improvement in mortality. Althoughcardiac causes accounted for the majority of deaths (46%), manyof these patients had a preceding catheter-related infection,particularly serious bacteremias requiring hospitalization.Septicemias have been found to double the risk of death fromany cause and increase the future risk of death from septicemiaby 5 to 9 times (2). Mortality due to septicemia in a dialysispatient is 30-fold to 50-fold higher than in the general population(46). Patients on hemodialysis are often considered frail and"immunocompromised" (47). Thus, serious infection may furthercompromise a poor baseline health state, rendering them lessable to cope with intercurrent illnesses. We postulated thatbecause the PT-allocated group was protected from serious infections(bacteremias) they may have maintained a better general healthstate than patients in the placebo group, who suffered fromcatheter-related infections. This trial was designed to determinewhether topical PT antibiotic ointment applied to the centralvenous catheter insertion site could reduce the incidence ofcatheter-related infections and was found to do so. We alsofound an association between the use of PT and improved survival.Because survival was identified a priori to be a secondary endpointrather than the primary endpoint further evaluation is necessaryin this area due to the relatively low event rate and becauseother factors may have played a role in the observed differencein survival between the two study groups.
Correlations between organisms cultured from the skin at thecatheter exit site and those subsequently isolated from thetip (17,19,48) suggest a pathogenic role between exit site colonizationand bacteremia. Organisms may enter the bloodstream by migratingfrom the skin insertion site along the external surface of thecatheter, colonize the lumen and distal intravascular tip, andultimately lead to a serious bacteremia. Our study demonstrateda lower rate of S. aureus nasal and catheter colonization; thismay therefore explain, in part, the lower rate of S. aureusinfections in our study compared with some of the literature(9,12,13,17). However, our study is consistent with others withstaphylococcal species being the predominant (60 to 100%) bacterialisolates responsible for the infectious events (8,9,13,32,46).The reasons for such a low rate of S. aureus colonization comparedwith the earlier literature is unclear; however, we speculatethat shifts in organism types colonizing these sites may berelated to the rigorous cleansing around the exit sites withagents such as chlorhexidine (49). The organisms obtained duringthe baseline and surveillance swabs (nares and exit site) arebeing identified by molecular subtyping techniques (pulsed fieldgel electrophoresis) for ongoing work to gain a better understandingof this change in flora. PT was effective in a dialysis populationwhere the catheter exit sites were colonized with a varietyof organisms (Table 5). The benefits of the triple antibioticformulation include providing the broad-spectrum coverage tomake this possible and the reduced likelihood of organisms developingresistance (28). Topical agents with narrower microbial coveragemay have been less effective. However, the primary concern withthe use of broad-spectrum antibiotics is the potential for increasingyeast infection. As noted in Table 5, there was no differencein the number of yeast infections in the placebo versus PT group;most individuals who did develop a yeast infection were immunocompromisedor had a predisposing risk factor. One patient in the placebogroup and two in the PT group experienced a yeast-related infection.The patient in the placebo group with a yeast-related infectionhad an embedded piece of catheter and was previously infectedwith yeast species. In the PT group, one was HIV-positive andone was on long-term tapering steroids for four previous failedtransplants. In patients predisposed to yeast infection, multipleand/or broad-spectrum antibiotics, even topical, should be avoidedif possible.
The applications of our study must be considered in the contextof hemodialysis patients using a permanent tunneled internaljugular dialysis catheter (none of our patients had temporaryor subclavian lines). This study population received skin preparationwith chlorhexidine only, thus we cannot answer questions ofsuperiority of PT versus another agent for infection prophylaxis.Lastly, we did not formally evaluate the relationships betweenrecurrent catheter problems, recurrent infection, dialysis adequacy,and its effect on the probability of infection; however, weare encouraged by our analysis of time to first infection andbacteremia when comparing the effect of PT with placebo in preventingcatheter-related infections.
In summary, we have demonstrated a significant decrease in catheter-relatedinfections, bacteremic episodes, catheter loss, and hospitalizationswhile possibly influencing mortality by the use of PT to thecatheter exit site in catheter-dependent chronic hemodialysispatients. Application of this ointment for prophylactic treatmentof permanent hemodialysis catheters should be considered, givenits simplicity, low expense, and potential to dramatically reduceinfectious complications and their related costs.
Acknowledgments
We would like to acknowledge the valuable assistance of CynthiaBhola, Nancy Perkins, JoAnne Burt, Melanee Eng Chong, ChrisJohnston, and the hemodialysis staff. Polysporin Triple andmatching placebo were provided by Pfizer Consumer Healthcare,Pfizer Canada Inc. Study Locations: Department of Medicine,Division of Nephrology, University Health Network, The TorontoGeneral Hospital; and Department of Medicine, Division of Nephrology,Sunnybrook and Womens’s College Health Sciences Centre,Toronto, Canada. This study was supported in part by Physician’sServices Incorporated grant R00-08.
DESchaubel, Fenton SSA: Trends in mortality rates on hemodialysis in Canada, 1981–1997. Kidney Int 57: S66–S73, 2000
Powe NR, Jaar B, Furth SL, Hermann J, Briggs W: Septicemia in dialysis patients: Incidence, risk factors, and prognosis. Kidney Int 55: 1081–1099, 1999[CrossRef][Medline]
Bloembergen BE, Port FK: Epidemiological perspective on infection in chronic dialysis patients. Adv Renal Replac Ther 3: 201–207, 1996
U.S. Renal Data System: 2001 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD, National Institutes of Health, NIDDK, 2001
Mailloux LU, Bellucci AG, Wilkes BM, Napolitano B, Mossey RT, Lesser M, Bluestone PA: Mortality in dialysis patients: Analysis of the causes of death. Am J Kidney Dis 18: 326–335, 1991[Medline]
Kessler M, Hoen B, Mayeux D, Hestin D, Fontenaille C: Bacteremia in patients on chronic hemodialysis: A multicentre prospective survey. Nephron 64: 95–100, 1993[Medline]
Marr Ka, Kong L, Fowler VG, Gopal A, Sexton DJ, Conlon PJ, Crey GR: Incidence and outcome of Staphylococcus aureus in hemodialysis patients. Kidney Int 54: 1684–1689, 1998[CrossRef][Medline]
Kairaitis LK, Gottlieb T: Outcome and complications of temporary hemodialysis catheters. Nephrol Dial Transplant 14: 1710–1714, 1999[Abstract/Free Full Text]
Hoen B, Paul-Dauphin A, Hestin D, Kessler M: EPIBACDIAL: A multicentre prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol 9: 869–876, 1998[Abstract]
Chow JW, Yu VL: Staphylococcus aureus nasal carriage in hemodialysis patients. Its role in infection and approaches to prophylaxis. Arch Intern Med 149: 1258–1262, 1989[CrossRef][Medline]
Yu VL, Goetz A, Wagener M, Smith PB, Rihs JD, Hanchett J, Zuravlef JJ: Staphylococcus aureus nasal carriage and infection in patients on hemodialysis. N Engl J Med 315: 91–96, 1986[Abstract]
Beathard, G: Management of bacteremia associated with tunneled cuffed hemodialysis catheters. J Am Soc Nephrol 10: 1045–1049, 1999[Abstract/Free Full Text]
Marr KA, Sexton D, Conlon P, Corey GR, Schwab SJ, Kirkland KB: Catheter-related bacteremia and outcome of attempted catheter salvage in patients undergoing hemodialysis. Ann Intern Med 127: 275–280, 1997[Abstract/Free Full Text]
Saad TF: Bacteremia associated with tunneled, cuffed hemodialysis catheters. Am J Kidney Dis 34: 1114–1124, 1999[Medline]
Krishnasami Z, Carlton D, Bimbo L, Taylor ME, Balkovetz DF, Barker J, Allon M: Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution. Kidney Int 61: 1136–1142, 2002[CrossRef][Medline]
Levin A, Mason AJ, Jindal KK, Fong IW, Goldstein MB: Prevevention of hemodialysis subclavian vein catheter infections by topical providone-iodine. Kidney International 40: 934–938, 1991[Medline]
Boelaert JR, Van Landuyt HW, Godard CA, Daneels RF, Schurgers ML, Matthys EG, De Baere YA, Gheyle DW, Gordts BZ, Herwaldt LA: Nasal mupirocin ointment decreases the incidence of Staphylococcus aureus bacteremias in haemodialysis patients. Nephrol Dial Transplant 8: 235–239, 1993[Abstract/Free Full Text]
Sesso R, Barbosa D, Leme IL, Sader H, Canziani ME, Manfredi S, Draibe S, Pignatari AC: Staphylococcus aureus prophylaxis in hemodialysis patients using central venous catheter: Effect of mupirocin ointment. J Am Soc Nephrol 9: 1085–1092, 1998[Abstract]
Raad I, Darouiche R, Dypppuis J, Abi-Said D, Gabrielli A, Hachem R: Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. Ann Int Med 127: 267–274, 1997[Abstract/Free Full Text]
Maki DG, Stolz SM, Wheeler S, Mermel LA: Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. Ann Int Med 127: 257–266, 1997[Abstract/Free Full Text]
Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD: Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infections: a meta-analysis. JAMA 281: 261–267, 1999[Abstract/Free Full Text]
Sodemann K, Lubrich-Birker I, Berger O, Baumert J, Feldmer B, Von Hodenberg E: Gentamicin/sodium citrate mixture as antibiotic-lock technique for salvage and prevention of catheter related infections. A four year trial [Abstract]. J Am Soc Nephrol 8: 173A, 1997
Ash SR, Mankus RA, Sutton JM, Criswell RE, Crull CC, Velasquez KA, Smeltzer BD, Ing TS: Concentrated sodium citrate (23%) for catheter lock. Hemodial Int 4: 22–31, 2000
Sodemann K, Polaschegg HD, Feldmer B: Two years’ experience with Dialock and CLS (a new antimicrobial lock solution). Blood Purif 19: 251–254, 2001[CrossRef][Medline]
Ethier JH, Lindsay RM, Barre PE, Kappel JE, Carlisle EJ, Common A: Clinical practice guidelines for vascular access. J Am Soc Nephrol 10: S297–S305, 1999[Medline]
Preventing infections associated with indwelling intravascular access devices. Can CommunDis Rep 23S8: 1–7, 1997
Doern G, Ferraro MJ, Gilligan PH, Janda JM, Von Graevenitz A: Bacteriology. In: Manual of Clinical Microbiology, 7th ed., edited by Murray PR, Baron EJ, Pfaller M, Tenover F, Yolken R, Washington, ASM Press, 1996, pp 246–776
Mehta CR, Patel, NR: A network algorithm for the exact treatment of Fisher’s exact test in RxC contingency tables. J Am Stat Assn 78: 427–434, 1982[CrossRef]
Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data. New York, John Wiley, 1980
Laupacis A, Sackett DL, Roberts RS: An assessment of clinically useful measures of the consequences of treatment. J Engl J Med 318: 1728–1733, 1988[Medline]
Uldall PR, Dyck RF, Woods RN: A subclavian cannula for temporary vascular access for hemodialysis or plasmapheresis. Dial Transplant 8: 963–968, 1979
Taylor GD, McKenzie M, Buchanan-Chell M, Caballo L, Chui L, Kowalewska-Grochowska K: Central venous catheters as a source of hemodialysis related bacteremia. Infect Control Hosp Epidemiol 19: 643–646, 1998[Medline]
Dittmer ID, Sharp D, McNulty CAM, Williams AJ, Banks RA: A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia. Clin Nephrol 51: 34–39, 1999[Medline]
National Kidney Foundation. K/DOQI Clinical practice guidelines for vascular access, 2000. Am J Kidney Dis 27: S137–S181, 2001
Oliver MJ, Callery SM, Thorpe KE, Schwab SJ, Churchill DN: Risk of bacteremia from temporary hemodialysis catheters by site of insertion and duration of use: A prospective study. Kidney Int 58: 2543–3545, 2000[CrossRef][Medline]
Schwab SJ, Buller GL, McCann RL, Bollinger RR, Stickel DL: Prospective evaluation of a Dacron cuffed hemodialysis catheter for prolonged use. Am J Kidney Dis 11: 166–169, 1988[Medline]
Dhingra RK, Young EW, Hulbert-Shearon TE, Leavey SF, Port FK: Type of vascular access and mortality in U.S. hemodialysis patients. Kidney Int 60: 1443–1451, 2001[CrossRef][Medline]
Gilbart J, Perry CR, Slocombe B: High level mupirocin resistance in Staphylococcus aureus; evidence for two distinct isoleucyl-TRNA synthetases. Anitmicrob Agents Chemother 37: 32–38, 1993[Abstract/Free Full Text]
Zakrzewska-Bode A, Muytjens HL, Liem KD, Hoogkamp-Korstanje JA: Mupirocin resistance in coagulase-negative staphylococci after topical prophylaxis for the reduction of colonization of central venous catheters. J Hosp Infect 31: 189–193, 1995[CrossRef][Medline]
Ramos RL, Teixeira LA, Ormonde LR, Siqeira PL, Santos MS, Marangoni D, Figgueiredo AM: Emergence of mupirocin resistance in multiresistant Staphylococcus aureus clinical isolates belonging to Brazilian epidemic clone III:B:A. J Med Microbiol 48: 303–307, 1999[Medline]
Pemberton LB, RossV, Cuddy P, Kremer H, Fessler T, McGurk E: No difference in catheter sepsis between standard and antiseptic central venous catheters. A prospective randomized study. Arch Surg 131: 986–989, 1996[Abstract]
Bach A, Schmiddt H, Bottiger B, Schrieber B, Bohrer H, Motsch J, Martin E, Sonntag HG: Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters. J Antimicrob Chemother 37: 315–322, 1996[Abstract/Free Full Text]
Sampath L, Tambe S, Modak S: In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: Evaluation of the risk of bacterial resistance to the antimicrobials in the catheters. Infect Control Hosp Epidemiol 22: 640–646, 2001[CrossRef][Medline]
Tattawasart U, Maillard JY, Furr JR, Russell AD: Development of resistance to chlorhexidine diacetate and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility. J Hosp Infect 42: 219–229, 1999[CrossRef][Medline]
Sarnak MJ, Jaber BL: Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 58: 1758–1764, 2000[CrossRef][Medline]
Vandholder R, Ringoir S: Infectious morbidity and defects of phagocytic function in end stage renal disease: A review. J Am Soc Nephrol 3: 1541–1554, 1993[Abstract]
Goldman DA, Pier GB: Pathogenesis of infections related to intravascular catheterization. Clin Microbiol Rev 6: 176–192, 1993[Abstract/Free Full Text]
Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S: Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: A meta-analysis. Ann Intern Med 136: 792–801, 2002[Abstract/Free Full Text]
Received for publication June 5, 2002.
Accepted for publication September 6, 2002.
This article has been cited by other articles:
M. T. James, J. Conley, M. Tonelli, B. J. Manns, J. MacRae, B. R. Hemmelgarn, and for the Alberta Kidney Disease Network Meta-analysis: Antibiotics for Prophylaxis against Hemodialysis Catheter-Related Infections
Ann Intern Med,
April 15, 2008;
148(8):
596 - 605.
[Abstract][Full Text][PDF]
A. X. Garg, T. Greene, and N. W. Levin A well-conducted randomized trial that establishes no benefit of therapy is an important medical advance
Nephrol. Dial. Transplant.,
January 1, 2008;
23(1):
52 - 55.
[Full Text][PDF]
A. J. Bleyer Use of Antimicrobial Catheter Lock Solutions to Prevent Catheter-Related Bacteremia
Clin. J. Am. Soc. Nephrol.,
September 1, 2007;
2(5):
1073 - 1078.
[Abstract][Full Text][PDF]
C. E. Lok, D. Appleton, C. Bhola, B. Khoo, and R. M. A. Richardson Trisodium citrate 4%--an alternative to heparin capping of haemodialysis catheters
Nephrol. Dial. Transplant.,
February 1, 2007;
22(2):
477 - 483.
[Abstract][Full Text][PDF]
K. Jindal, C. T. Chan, C. Deziel, D. Hirsch, S. D. Soroka, M. Tonelli, and B. F. Culleton CHAPTER 4: Vascular Access
J. Am. Soc. Nephrol.,
March 1, 2006;
17(3_suppl_1):
S16 - S23.
[Full Text][PDF]
R. N. Foley, H. Guo, J. J. Snyder, D. T. Gilbertson, and A. J. Collins Septicemia in the United States Dialysis Population, 1991 to 1999
J. Am. Soc. Nephrol.,
April 1, 2004;
15(4):
1038 - 1045.
[Abstract][Full Text][PDF]
Top
Abstract
Introduction
7 d was called "incident catheter," and others were called "prevalent catheter"). Patient randomization was performed at an independent central randomization facility via a computer-generated random number list, using blocked randomization with a block size of 4. Written informed consent was obtained from all patients or their legal representative. The study protocol was approved by the Research Ethics Boards of the participating Canadian institutions and the funding agency. The use of a placebo ointment on a chlorhexidine-cleansed site was justified at the time, as the study was designed and approved before the Canadian Society of Nephrology guidelines for vascular access (26) were published. 
of 0.05 (based on the previous year’s average of 0.7 infections/patient per yr between the two institutions). The follow-up period for the primary endpoint was defined from the beginning of the study to be 6 mo. A follow-up period of 12 mo was considered too long for reliable results, because beyond 6 mo the rate of infection appears to decline, the need for secondary catheters rises, and there is substantially greater risk that confounding factors could cloud the study results. We assessed differences in proportions using Fisher’s exact test and the number of infections per 1000 catheter-days using the exact binomial test (29). Time-to-event distributions were estimated using the Kaplan-Meier method and compared using the log-rank test (30). The relative risk reduction and number of patients needed to treat (NNT) to prevent one infection, bacteremia, and death were determined (31). Analyses were based on an intention-to-treat approach, except for the exclusion of seven blinded subjects who never started treatment. Analyses were performed using SAS, version 8.e (SAS Institute, Cary, NC). 
