Systematic Review: Antimicrobial Urinary Catheters To Prevent Catheter-Associated Urinary Tract Infection in Hospitalized Patients

Key Summary Points Randomized or quasi-randomized clinical trials of antimicrobial urinary catheters currently marketed in the United States (i.e., nitrofurazone-coated and silver alloycoated catheters) provide little or no data on these devices' effect on symptomatic urinary tract infection, morbidity, secondary bloodstream infection, mortality rates, or associated health care costs. Both nitrofurazone-coated and silver alloycoated catheters seem to reduce the development of asymptomatic bacteriuria during short-term (<30 days) use, in comparison with latex or silicone control catheters. The magnitude of this effect varies among studies, seemingly in relation to the type of antimicrobial catheter (nitrofurazone or silver), patient sample (urology or other), control group bacteriuria rate (high or low), and type of control catheter (latex or silicone). No trials directly compared nitrofurazone-coated and silver alloycoated catheters. Therefore, assessments of the comparative efficacy of nitrofurazone-coated and silver alloycoated catheters should be made cautiously. The clinical utility and cost-effectiveness of antimicrobial urinary catheters must be assessed in well-designed, adequately powered, randomized clinical trials. Indwelling urinary catheters, which are used in 15% to 25% of short-term care patients during their hospitalization, confer a predisposition to bacteriuria (1-3). Catheter-associated urinary tract infection (UTI) is the most common type of hospital-acquired infection, accounting for approximately 40% of such infections and for most of the 900000 patients with nosocomial bacteriuria in U.S. hospitals each year (2). Adverse consequences include local and systemic morbidity, secondary bloodstream infection, death, a reservoir of drug-resistant microorganisms, and increased health care costs (1-4). Among catheterized patients, clinical manifestations of UTI (pain, urgency, dysuria, fever, and leukocytosis) are uncommon even when bacteriuria or funguria is present and are no more prevalent with positive urine culture results than with negative results (5). Fewer than the traditionally estimated 1% to 5% of catheter-associated bacteriuria episodes produce secondary bloodstream infection (5). However, secondary bloodstream infection almost always involves gram-negative bacilli, making catheter-associated bacteriuria the primary source for nosocomial gram-negative bacteremia (6-8). The effect of catheter-associated bacteriuria on mortality is unclear. The 3-fold mortality increase documented in 1 study (9) was not observed in other studies (5, 10-12). Many deaths among patients with secondary bloodstream infection from catheter-associated bacteriuria are probably due to underlying diseases (6, 12). Although colonized catheter systems may provide a reservoir of resistant microorganisms for transmission to other patients (3, 13), the importance of this process to nosocomial infections is undefined. Estimated costs and length of stay attributable to catheter-associated bacteriuria vary greatly (13, 14). Only a fraction of catheter-associated bacteriuria episodes come to physicians' attention. Most that do are treated despite the absence of symptoms (5), and evidence suggests that untreated episodes do not increase costs or length of hospitalization (13). Recent data indicate that even treated episodes increase costs by a mean of only $589 (median, $356) without prolonging hospitalization (13). Nonetheless, the enormous aggregate numbers of episodes make catheter-associated bacteriuria a clinically significant medical problem (1-4). Preventive efforts have included reduced catheter use (15); proper catheter maintenance (16); and technical modifications, including antimicrobial catheter coatings (17, 18). Four antimicrobial urinary catheters are currently marketed in the United States. They are coated with silver alloy (3 latex- or silicone-base catheters) or nitrofurazone, a nitrofurantoin-like drug (1 silicone-base catheter). Two previous meta-analyses of randomized, controlled trials (RCTs) of antimicrobial catheters concluded that trial quality was modest, that silver oxidecoated catheters (which are no longer marketed) lack efficacy, and that silver alloycoated catheters are protective, and no conclusions were made about the prevention of symptomatic UTI, bloodstream infection, or death (19, 20). However, these meta-analyses included only trials published through 1993 (19) or 2000 (20). Moreover, they did not address nitrofurazone-coated catheters or assess outcomes in relation to study characteristics or specific microorganisms, specifically bacteremia-associated gram-negative bacilli. Accordingly, we conducted a systematic review of clinical trials to address these important questions. Methods Search and Selection Processes Sources included MEDLINE (since 1966), BIOSIS (since 1998), the Cochrane Library (since 1996), www.clinicaltrials. gov (since inception), and abstracts from meetings of relevant professional societies (as available since 1998). Search terms included catheter and urinary tract infection, limited when possible to human and clinical trial but not to English language. We contacted manufacturers of currently marketed antimicrobial catheters and experts for relevant data, and we reviewed bibliographies from these sources and from our personal files. We searched such gray literature (21) because of the anticipated paucity of published RCTs and because both previous meta-analyses included trials reported only as abstracts (19, 20). An author retrieved and screened publications that reported clinical trials of antimicrobial catheters. The latest search date was 5 June 2005. We required trials to be randomized or quasi-randomized and to involve an antimicrobial urinary catheter that is currently marketed in the United States, or its equivalent, for short-term (<30 days) (2) bladder drainage. Currently marketed catheters include the Lubricath IC (silver hydrogelcoated latex) and Lubrisil IC (silver hydrogelcoated silicone) catheters (Bard Medical, Covington, Georgia), the Kendall DOVER silver Foley catheter (silver hydrogel silicone) (Tyco Healthcare, Mansfield, Massachusetts), and the RELEASE-NF catheter (nitrofurazone-coated silicone) (Rochester Medical Corp., Stewartville, Minnesota). We excluded studies if data were insufficient for outcome assessment or if the catheter system included antimicrobial modifications other than the catheter coating (20). We accepted quasi-randomized trials because of the paucity of qualifying conventional RCTs and because previous meta-analyses included them (19, 20). Data Extraction An author assessed reports of qualifying studies for locale, funding source, study design (including allocation method, allocation concealment, and blinding), study sample (including age, sex, underlying diagnoses, reason for catheter use, and similarity of comparison groups), inclusion and exclusion criteria (before and after enrollment), definition of catheter-associated UTI, UTI ascertainment methods, duration of catheter use, and outcomes. Outcomes included proportion developing symptomatic UTI (primary outcome) or bacteriuria or funguria (secondary outcome, hereafter called bacteriuria), both overall and by organism type. We also sought data on secondary bloodstream infection, death, adverse events, selection for resistant microorganisms, and costs. We used a standardized data form. We sought relevant details that were not included in the primary report from previous meta-analyses, trialists, and study sponsors. We discussed disagreements about article content and quality until we reached consensus. We assessed study quality according to Schulz and colleagues (22). In addition, we assessed whether studies were blinded or reported intention-to-treat analyses and the proportion lost to follow-up. We presumed that trials not described as blinded were nonblinded. To estimate organism-specific outcomes when more isolates were reported than bacteriuria episodes, we assumed that episodes involved the reported microbial types in proportion to their respective prevalences. We based outcome analyses on the earliest reported result at day 5 or later to minimize the effect of patient dropout while capturing a usable number of events. For a trial that randomly assigned catheter type by ward and did not track participants (catheters) individually, we analyzed outcomes on an intention-to-treat basis as the number of catheter-associated bacteriuria episodes occurring on study wards divided by the number of study catheters used on study wards (14). For sensitivity analysis, we stratified trials by catheter coating. We further stratified silver catheter trials by publication year, with 1995 as the partition date, which divided the longest interval between any 2 trials (1993 to 1998) and yielded similar-sized comparison groups, with 1 group encompassing the past decade. Statistical Analysis We estimated the risk ratio (fixed effects) and associated 95% CI for individual studies by using Review Manager (RevMan) software, version 4.2 (Cochrane Collaboration, Oxford, United Kingdom). Because of the extensive heterogeneity among studies with respect to study design, patient samples, and data reporting, we did not perform quantitative pooling of results. Absolute risk reduction was the between-group difference in outcome incidence. We assessed the effect of various study characteristics on outcomes after stratifying the studies according to the characteristics of interest. We tested 2-group comparisons involving continuous variables by using the Mann-Whitney U test. Role of the Funding Source The corporate sponsor, Rochester Medical Corp. (manufacturer of the nitrofurazone-coated catheter), had no role in the design, analysis, or reporting of the study or in the decision to approve publication of the finished manuscript. Results Search Results The search identified 665 possibly relevant artic