Mark E. Rupp

Effect of a Second-Generation Venous Catheter Impregnated with Chlorhexidine and Silver Sulfadiazine on Central Catheter–Related Infections: A Randomized, Controlled Trial

Context Bacterial colonization of central venous catheters is relatively common, and subsequent bacteremia is a serious iatrogenic complication of critical illness. Initial studies of antimicrobial-coated catheters have suggested that this approach might decrease catheter-associated infection. Contribution This randomized, double-blind, controlled study of a new antiseptic-coated catheter versus an uncoated catheter shows a substantial decrease in bacterial colonization in patients receiving the coated device. Caution The study was unable to show a substantial decrease in bloodstream infections, possibly because of the low infection rate as a result of meticulous aseptic techniques used during catheter insertion. The Editors Infections associated with central venous catheters are a substantial problem. Each year in the United States, at least 80 000 patients in intensive care units experience central venous catheterassociated bacteremia (1, 2). These infections are associated with an overall attributable mortality of approximately 3% (3), but estimates vary from 0% to greater than 30% depending on patient population, definitions, and pathogens (4). The attributable cost per infection ranges from

Improving Cleaning of the Environment Surrounding Patients in 36 Acute Care Hospitals

3240 to more than

Outbreak of Bloodstream Infection Temporally Associated with the Use of an Intravascular Needleless Valve

50 000 (5-8). Many strategies have been used to prevent catheter-associated infection. These measures can be divided into 2 groups: those that prevent microbes from gaining access to the catheters and those that discourage microbes from adhering and proliferating on the catheter, such as coating the catheters with various antimicrobial agents. The latter approach has shown promise and has included the use of chlorhexidine and silver sulfadiazine. In a randomized clinical trial, Maki and colleagues (9) observed a statistically significant decrease in colonization and bacteremia in patients who received a catheter coated with chlorhexidine and silver sulfadiazine compared with controls who received an uncoated catheter. In a randomized, comparative trial, Darouiche and colleagues (10) found that catheters impregnated with minocycline and rifampin were associated with fewer infectious complications than catheters coated with chlorhexidine and silver sulfadiazine. However, one of the main differences between the catheters was that the chlorhexidinesilver sulfadiazine coating involved only the external surface of the catheter, whereas the minocycline and rifampin catheter was coated on the internal and external surfaces. More recently, a second-generation antiseptic catheter was formulated that increased the chlorhexidine concentration on the external surface of the catheter 3-fold and incorporated chlorhexidine on the luminal surface of the catheter, extension lines, and hubs. This trial was conducted to assess the efficacy and safety of the second-generation antiseptic catheter compared with an uncoated control catheter. Methods Patients and Study Design This study was a randomized, double-blind, controlled trial conducted between July 1998 and June 2001 at 9 university-affiliated hospitals. The objective was to determine whether the second-generation antiseptic central venous catheter was effective in preventing microbial colonization and bloodstream infection in comparison with an uncoated control catheter. The null hypothesis was that the incidence of bloodstream infection would be the same or worse for the patients who received the antiseptic catheter compared with the patients who received the control catheter. Secondary goals consisted of product safety evaluation, assessment of the microbiology of catheter-associated infection, and microbial susceptibility to chlorhexidine and silver sulfadiazine. The institutional review boards at each hospital approved the protocol. Adult patients who were cared for in critical care units and who required a triple-lumen central venous catheter were eligible for participation. Patients who were pregnant, were allergic to chlorhexidine or sulfa drugs, were hospitalized for burn injuries, had a chronic inflammatory skin disorder at the catheter insertion site, were suspected of having a catheter-associated infection, or were enrolled in another investigational trial were not eligible for participation. All patients or their authorized surrogates granted informed consent. The study sample size was calculated on the basis of an expected catheter-related bloodstream infection rate of approximately 4.5% in the control group and 1.5% in the antiseptic catheter group. Allowing for a 12% dropout rate, 793 patients were required to yield a study with an 80% power at the 0.05 level of statistical significance. Catheters All catheters were 7-French, 20-cm long polyurethane triple-lumen central venous catheters manufactured by Arrow International, Inc. (Reading, Pennsylvania). Control catheters were standard, uncoated triple-lumen catheters. Antiseptic catheters (ARROWgard II Blue Plus, Arrow International, Inc.) were coated with chlorhexidine acetate and silver sulfadiazine on the external surface and chlorhexidine and chlorhexidine acetate on the luminal surfaces. All catheters were indistinguishable in appearance and packaging. Randomization, Catheter Insertion, and Care Procedures Patients were randomly assigned to receive an individually numbered catheter and had an equal probability of assignment to either group. The randomization code was developed by using a computerized random-number generator to select permuted blocks. The block length was 4. Randomization stratification ensured that antiseptic and control catheters were evenly distributed in the de novo and guidewire exchange groups. Patients were randomly assigned in a 1:1 ratio within each of the study centers. Catheter allocation was concealed, and patients, study personnel, and all health care workers were unaware of whether the catheters were coated or uncoated. A subset of patients at each institution (approximately one third of patients) was allowed to receive an initial study catheter through guidewire exchange. Four institutions were also allotted a small number of exchange insertions in which a study catheter could be exchanged for a matched study catheter (randomization and blinding were protected). Figure 1 shows the distribution of patients. Catheters were inserted by using full sterile barrier precautions, which included the operators wearing a sterile long-sleeve gown, sterile gloves, hat, and mask, and using a large sterile drape. Before insertion, the skin was cleansed with 10% povidone-iodine (chlorhexidine-based antiseptics were not approved by the U.S. Food and Drug Administration for insertion-site preparation). Before a study catheter was inserted over a guidewire into a preexisting site, the hub of the first catheter was cleansed with povidone-iodine. The tip of the preexisting catheter was submitted for microbiological testing. Insertion sites were dressed with a transparent polyurethane dressing (OpSite 3000, Smith & Nephew, Inc., Largo, Florida). No antimicrobial ointment was applied at the insertion site. Depending on institutional routine, dressings were changed every 72 to 96 hours using a standardized kit. At the time of dressing change, the insertion site was cleansed with povidone-iodine. The patients attending physician made the decision to remove the catheter. Figure 1. Distribution of initial study catheters by type and method of insertion. Measurements and Definitions At the time of catheter insertion, the following data were recorded: patient demographic characteristics, indication for catheter insertion, underlying medical conditions, indication for admission to the intensive care unit, length of hospital stay and length of intensive care unit stay, and severity of illness score (Acute Physiology and Chronic Health Evaluation [APACHE] II score). Study catheters were inspected daily. Local and systemic signs and symptoms of infection were recorded. The presence of other intravascular and indwelling devices was noted, and the antibiotics that were administered were recorded. At the time of catheter removal, a 20-cm2 circular template was placed at the catheter insertion site and a moistened swab (Culturette, Becton Dickinson and Co., Sparks, Massachusetts) was used to sample the pericatheter insertion site. The swab was sent to the institutional microbiology laboratory, where it was used to inoculate a blood agar plate. Catheters were removed by using an aseptic technique. The subcutaneous portion of the catheter was cut from the rest of the catheter, and the 2 portions were placed in separate sterile plastic bags for transport to the laboratory. The subcutaneous portion of the catheter was divided into four 2.5-cm segments. A neutralizing media (D/E Neutralizing Broth or Agar, Remel, Lenexa, Kansas) was used to minimize any potential antimicrobial carryover effect. Proximal and distal segments were cultured by using the roll-plate method (11), and similarly, proximal and distal segments were cultured by using a sonication technique (12). At 2 centers, the catheter hubs were cultured by using moistened swabs. Blood cultures were obtained from the catheter and from a peripheral vein on any patient with suspected catheter-associated infection. Signs and symptoms of a catheter-associated infection included fever (temperature > 38 oC) without another obvious source and local signs of infection, such as erythema, cellulitis, purulent drainage, or excessive tenderness. All microbes recovered from cultures of the patients blood, catheter, skin, or other sites were shipped to a central laboratory (University of Iowa, Iowa City, Iowa) for confirmatory identification and susceptibility testing. Catheters were defined as colonized if cultures revealed at least 15 colony-forming units per segment by the roll-plate method or at least 100 colony-forming units per segment by the sonication method. Catheter-related bloodstream infection was defined as catheter colonization with positive blo

Epidemiology and Predictors of Multidrug-Resistant Community-Acquired and Health Care-Associated Pneumonia

OBJECTIVE The prevalence of serious infections caused by multidrug-resistant pathogens transmitted in the hospital setting has reached alarming levels, despite intensified interventions. In the context of mandates that hospitals ensure compliance with disinfection procedures of surfaces in the environment surrounding the patient, we implemented a multihospital project to both evaluate and improve current cleaning practices. DESIGN Prospective quasi-experimental, before-after, study. SETTING Thirty-six acute care hospitals in the United States ranging in size from 25 to 721 beds. METHODS We used a fluorescent targeting method to objectively evaluate the thoroughness of terminal room disinfection cleaning before and after structured educational and procedural interventions. RESULTS Of 20,646 standardized environmental surfaces (14 types of objects), only 9,910 (48%) were cleaned at baseline (95% confidence interval, 43.4-51.8). Thoroughness of cleaning at baseline correlated only with hospital expenditures for environmental services personnel (P = .02). After implementation of interventions and provision of objective performance feedback to the environmental services staff, it was determined that 7,287 (77%) of 9,464 standardized environmental surfaces were cleaned (P < .001). Improvement was unrelated to any demographic, fiscal, or staffing parameter but was related to the degree to which cleaning was suboptimal at baseline (P < .001). CONCLUSIONS Significant improvements in disinfection cleaning can be achieved in most hospitals, without a substantial added fiscal commitment, by the use of a structured approach that incorporates a simple, highly objective surface targeting method, repeated performance feedback to environmental services personnel, and administrative interventions. However, administrative leadership and institutional flexibility are necessary to achieve success, and sustainability requires an ongoing programmatic commitment from each institution.

Molecular epidemiology in the public health and hospital environments

BACKGROUND Needleless intravascular catheter connector valves have been introduced into clinical practice to minimize the risk of needlestick injury. However, infection-control risks associated with these valves may be underappreciated. In March 2005, a dramatic increase in bloodstream infections was noted in multiple patient care units of a hospital in temporal association with the introduction of a needleless valve into use. METHODS Surveillance for primary bloodstream infection was conducted using standard methods throughout the hospital. Blood culture contamination rates were monitored. Cultures were performed using samples obtained from intravascular catheter connector valves. RESULTS The relative risk of bloodstream infection for the time period in which the suspect connector valve was in use, compared with baseline, was 2.79 (95% confidence interval, 2.27-3.43). In critical care units, the rate of primary bloodstream infection increased with the introduction of the valve from 3.87 infections per 1000 catheter-days to 10.64 infections per 1000 catheter-days (P<.001), and it decreased to 5.59 infections per 1000 catheter-days (P=.02) in the 6 months following removal of the device from use. Similarly, in inpatient nursing units, the rate of bloodstream infection increased from 3.47 infections per 1000 catheter-days to 7.3 infections per 1000 catheter-days (P=.02) following introduction of the device, and it decreased to 2.88 infections per 1000 catheter-days (P=.57) following removal of the device from use. Similar events occurred in the cooperative care units. The rate of blood culture contamination did not substantially change over the course of the study. Of 37 valves that were subjected to microbiological sample testing, 24.3% yielded microbes, predominantly coagulase-negative staphylococci. CONCLUSION A significant association between primary bloodstream infection and a needleless connector valve was observed. Evaluation of needleless connector valves should include a thorough assessment of infection risks in prospective randomized trials prior to their introduction to the market.

Utilization of the internal transcribed spacer regions as molecular targets to detect and identify human fungal pathogens

ABSTRACT There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from January 2010 to December 2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate whether HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score-adjusted multivariate analyses were performed. A total of 521 patients (50.5% CAP and 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDROs were isolated in 20 (3.8%) patients overall, and MDROs occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. The presence of an MDRO was not associated with HCAP classification (odds ratio [OR] = 1.95; 95% confidence interval [95% CI], 0.66 to 5.80; P = 0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48-h hospitalization in the last 90 days). Independent predictors of MDRO included the following: Pseudomonas aeruginosa colonization/infection in the previous year (OR = 7.43; 95% CI, 2.24 to 24.61; P < 0.001), antimicrobial use in the previous 90 days (OR = 2.90; 95% CI, 1.13 to 7.45; P = 0.027), admission from a nursing home (OR = 4.19; 95% CI, 1.55 to 11.31; P = 0.005), and duration of hospitalization in the previous 90 or 180 days (P = 0.013 and P = 0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.

Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance.

The increasing speed and ease of genomic sequencing coupled with available funding to sequence multiple, unrelated strains of the same species will lead inevitably to the identification of candidate genes that can be used as molecular typing tools (MLST, SLST, microarray approach). However, it is important to note that even the most sophisticated typing tool should never replace a full epidemiologic investigation in which all available information is taken into account. Nevertheless, the typing methods discussed in this article and those yet to be developed have significantly improved the quality of health care worldwide.