Michael W. Climo

Effect of Daily Chlorhexidine Bathing on Hospital-Acquired Infection

BACKGROUND Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs). METHODS We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine-impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis. RESULTS A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period. CONCLUSIONS Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.).

Hospital-wide Restriction of Clindamycin: Effect on the Incidence of Clostridium difficile-Associated Diarrhea and Cost

Clostridium difficile is an important cause of nosocomial infection and is the organism most often linked to antibiotic-associated diarrhea and pseudomembranous colitis [1-3]. As many as 25% of cases of nosocomial diarrhea may be caused by C. difficile, leading to increased hospital costs, morbidity, and mortality [2-5]. Acquisition of C. difficile may result in asymptomatic carriage or more clinically significant manifestations, including antibiotic-associated diarrhea, colitis, pseudomembranous colitis, and toxic megacolon [6-9]. The most frequently identified risk factor for the development of C. difficile-associated diarrhea is the antecedent use of antibiotics that alter the normal intrinsic colonic microflora. Antibiotics commonly associated with C. difficile-associated diarrhea include penicillins, cephalosporins, and clindamycin [2, 3, 10-12]. Previous attempts to control nosocomial outbreaks of C. difficile-associated diarrhea have included emphasis on handwashing, enforced barrier precautions, enhanced educational initiatives, and increased environmental cleaning [12-14]. Recently, several investigations showed a substantial decrease in the incidence of C. difficile-associated diarrhea after hospital formulary restriction of clindamycin [11, 15]. Aside from the issue of efficacy, hospital formulary control of antibiotics as a strategy to decrease the incidence of nosocomial infections raises several other questions. What effect does restriction have on the use of other antibiotics? Does restriction of certain classes of antibiotics lead to increased use of more expensive antimicrobial agents? Does formulary control save money? Does restriction affect the antimicrobial susceptibility of nosocomial isolates? Beginning in 1993, our hospital had an unusually high number of cases of nosocomial C. difficile-associated diarrhea, which continued despite the use of barrier precautions, educational programs, and enhanced terminal cleaning of patient rooms. When our investigation identified clindamycin use as a significant risk factor among hospitalized patients, we instituted hospital-wide restriction of clindamycin as an infection control measure. In this study, we investigated the effects of hospital formulary control on the incidence of C. difficile-associated diarrhea and the antimicrobial susceptibility of nosocomial isolates of C. difficile. We also examined the overall economic impact of such restrictions on antibiotic use. Methods The Hunter Holmes McGuire Veterans Affairs Medical Center is a 703-bed tertiary care hospital affiliated with the Medical College of Virginia in Richmond, Virginia. Infection control at the hospital is directed by the hospital epidemiologist (a physician) and administered by four infection control nurses. The monthly incidence of C. difficile-associated diarrhea for the past 10 years is known because of the routine review of C. difficile cytotoxin assay results or stool cultures positive for C. difficile from patients with symptomatic diarrhea. In November 1993, we initiated a prospective cohort study. All inpatients who had been hospitalized for at least 48 hours and had had stool samples sent to the microbiology laboratory for C. difficile cytotoxin assay were studied. Case-patients were defined as patients who had diarrhea (three or four loose [unformed] stools) within a 24-hour period, a history of antibiotic use within 8 weeks, and a positive result on a cytotoxin assay. Symptomatic patients with negative results on cytotoxin assay with or without a history of antibiotic use were designated as controls. Hospital charts, microbiological laboratory test results, and hospital pharmacy records were reviewed to obtain data on demographic variables; admitting service and diagnosis; documented infections; use of antibiotics before the onset of diarrhea; use of medications, including antacids, H2 blockers, and stool softeners; concurrent medical illnesses; invasive procedures and devices placed during hospitalization; presence of nasogastric or feeding tubes; ambulation status; room type (single or multi-bed); discharge status; and time from admission to onset of diarrhea. All stool samples were tested for cytotoxin production by using tissue cell culture assay [16]. Stool specimens with positive results on cytotoxin assay were cultured on CCFA (cycloserine, cefoxitin, fructose) blood agar [17] and incubated under anaerobic conditions for 48 hours. Isolates were presumptively identified as C. difficile by colony morphology, Gram stain, and biochemical identification with the RapID ANA II system (Innovative Diagnostic Systems, Norcross, Georgia). All isolates presumptively identified as C. difficile underwent C. difficile cytotoxin assay to verify toxin production. Isolates of C. difficile were maintained in chopped-meat broth and were typed by using pulsed-field gel electrophoresis after restriction endonuclease digestion with SmaI [18]. Pulsed-field gel electrophoresis of all isolates was completed over 20 hours with ramped pulsed-field times (initial 1 second to final 20 seconds). Antimicrobial susceptibility testing was done on all isolates by using an anaerobic agar dilution method according to guidelines from the National Committee for Clinical Laboratory Standards. Isolates were tested for susceptibility to clindamycin, metronidazole, and vancomycin and were considered resistant if the minimal inhibitory concentration (MIC) was greater than 4.0 g/mL for clindamycin and vancomycin or greater than 1.0 g/mL for metronidazole. The Fisher exact test was used to test for differences in proportions. The means of continuous variables were compared by using the Student t-test. Risk factors among the patient groups were compared by using the Cochran-Mantel-Haenszel chisquare test. Two-sided P values less than 0.05 were considered statistically significant. Results The Outbreak In September 1993, our hospital had the most cases of C. difficile-associated diarrhea (18 cases; 19 cases per 1000 discharges) seen since the introduction of surveillance for this condition. A review of hospital records showed a gradual increase in the number of cases of C. difficile-associated diarrhea since 1991 (Figure 1). The hospital averaged 4.3 cases of C. difficile-associated diarrhea per month in 1991 (4.5 infections per 1000 discharges), 6.4 cases per month in 1992 (6.5 infections per 1000 discharges), and 10.6 cases per month in 1993 (10.8 infections per 1000 discharges). The number of patients seen in the hospital between 1991 and 1996 was relatively constant, with a difference of less than 9% in the number of inpatient discharges per year over the entire period. Figure 1. Cases of Clostridium difficile -associated diarrhea, reported by quarter. C. difficile In response to the increasing number of cases of C. difficile-associated diarrhea, several control measures were instituted. All hospital staff were educated about the importance of barrier precautions and the appropriate isolation of patients with C. difficile-associated diarrhea. All patients identified as having C. difficile-associated diarrhea were placed in private rooms, and the use of barrier precautions was strictly enforced. Emphasis was placed on proper handwashing and the appropriate use of gloves. In addition, attempts were made to decrease environmental contamination with C. difficile; these attempts included terminal cleaning of the rooms of patients with C. difficile-associated diarrhea on selected wards. Despite these measures, the number of new cases of C. difficile-associated diarrhea remained high. In the first 3 months of 1994, 11.3 cases per month occurred and 25% of all stool specimens sent to the microbiology laboratory for C. difficile toxin assay had positive results. In March 1994, 35% of all stool specimens sent for C. difficile toxin assay had positive results. Over a 5-month period from November 1993 to March 1994, the microbiology laboratory received 159 stool samples for C. difficile toxin assay. Twenty-one of the samples were reported as formed stool and therefore were not satisfactory for testing. Of the remaining 138 samples, 52 (38%) were positive and 86 (62%) were negative for C. difficile toxin. Twenty percent of patients (10 of 50) had a relapse of C. difficile-associated diarrhea during the 5-month period. Patients identified with C. difficile-associated diarrhea were found on all wards of the hospital. Most patients (73%) were on medical wards (17.5 infections per 1000 discharges), but patients with C. difficile-associated diarrhea were also found on surgical wards (1.6 infections per 1000 discharges); on neurology wards (5.2 infections per 1000 discharges); in intensive care units (10.5 infections per 1000 discharges); and in long-term care facilities, including a nursing home and a spinal cord injury unit (24.4 infections per 1000 discharges). All patients identified with C. difficile-associated diarrhea were initially treated with oral metronidazole; regimens varied from 250 mg given orally every 8 hours to 500 mg given orally every 6 hours. Risk Factors for Clostridium difficile-Associated Diarrhea We did a prospective cohort study of 138 consecutive patients admitted to the hospital between November 1993 and March 1994 to determine the risk factors associated with C. difficile-associated diarrhea in hospitalized patients with symptomatic diarrhea. Increased age, bedridden status, documented underlying infection, and increased antibiotic use were significantly associated with C. difficile-associated diarrhea. Patients with C. difficile-associated diarrhea were older than controls (71 years compared with 63 years; P < 0.001) and were more likely to be bedridden (86% compared with 54%; P < 0.001; odds ratio, 5.2). No statistically significant differences were seen for admitting diagnosis, admitting service, discharge status, or death within 1 year of the onset of diarrhea. Patients with C. difficile-a

A multicenter intervention to prevent catheter-associated bloodstream infections.

BACKGROUND Education-based interventions can reduce the incidence of catheter-associated bloodstream infection. The generalizability of findings from single-center studies is limited. OBJECTIVE To assess the effect of a multicenter intervention to prevent catheter-associated bloodstream infections. DESIGN An observational study with a planned intervention. SETTING Twelve intensive care units and 1 bone marrow transplantation unit at 6 academic medical centers. PATIENTS Patients admitted during the study period. INTERVENTION Updates of written policies, distribution of a 9-page self-study module with accompanying pretest and posttest, didactic lectures, and incorporation into practice of evidence-based guidelines regarding central venous catheter (CVC) insertion and care. MEASUREMENTS Standard data collection tools and definitions were used to measure the process of care (ie, the proportion of nontunneled catheters inserted into the femoral vein and the condition of the CVC insertion site dressing for both tunneled and nontunneled catheters) and the incidence of catheter-associated bloodstream infection. RESULTS Between the preintervention period and the postintervention period, the percentage of CVCs inserted into the femoral vein decreased from 12.9% to 9.4% (relative ratio, 0.73; 95% confidence interval [CI], 0.61-0.88); the total proportion of catheter insertion site dressings properly dated increased from 26.6% to 34.4% (relative ratio, 1.29; 95% CI, 1.17-1.42), and the overall rate of catheter-associated bloodstream infections decreased from 11.2 to 8.9 infections per 1,000 catheter-days (relative rate, 0.79; 95% CI, 0.67-0.93). The effect of the intervention varied among individual units. CONCLUSIONS An education-based intervention that uses evidence-based practices can be successfully implemented in a diverse group of medical and surgical units and reduce catheter-associated bloodstream infection rates.

Selective Use of Intranasal Mupirocin and Chlorhexidine Bathing and the Incidence of Methicillin-Resistant Staphylococcus aureus Colonization and Infection Among Intensive Care Unit Patients

OBJECTIVE To determine whether the use of chlorhexidine bathing and intranasal mupirocin therapy among patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) would decrease the incidence of MRSA colonization and infection among intensive care unit (ICU) patients. METHODS After a 9-month baseline period (January 13, 2003, through October 12, 2003) during which all incident cases of MRSA colonization or infection were identified through the use of active-surveillance cultures in a combined medical-coronary ICU, all patients colonized with MRSA were treated with intranasal mupirocin and underwent daily chlorhexidine bathing. RESULTS After the intervention, incident cases of MRSA colonization or infection decreased 52% (incidence density, 8.45 vs 4.05 cases per 1,000 patient-days; P=.048). All MRSA isolates remained susceptible to chlorhexidine; the overall rate of mupirocin resistance was low (4.4%) among isolates identified by surveillance cultures and did not increase during the intervention period. CONCLUSIONS We conclude that the selective use of intranasal mupirocin and daily chlorhexidine bathing for patients colonized with MRSA reduced the incidence of MRSA colonization and infection and contributed to reductions identified by active-surveillance cultures. This finding suggests that additional strategies to reduce the incidence of MRSA infection and colonization--beyond expanded surveillance--may be needed.

Prevalence of the use of central venous access devices within and outside of the intensive care unit: Results of a survey among hospitals in the prevention epicenter program of the Centers for Disease Control and Prevention

OBJECTIVE To determine the prevalence of central venous catheter (CVC) use among patients both within and outside the ICU setting. DESIGN A 1-day prevalence survey of CVC use among adult inpatients at six medical centers participating in the Prevention Epicenter Program of the CDC. Using a standardized form, observers at each Epicenter performed a hospital-wide survey, collecting data on CVC use. SETTING Inpatient wards and ICUs of six large urban teaching hospitals. RESULTS At the six medical centers, 2,459 patients were surveyed; 29% had CVCs. Among the hospitals, from 43% to 80% (mean, 59.3%) of ICU patients and from 7% to 39% (mean, 23.7%) of non-ICU patients had CVCs. Despite the lower rate of CVC use on non-ICU wards, the actual number of CVCs outside the ICUs exceeded that of the ICUs. Most catheters were inserted in the subclavian (55%) or jugular (22%) site, with femoral (6%) and peripheral (15%) sites less commonly used. The jugular (33.0% vs 16.6%; P < .001) and femoral (13.8% vs 2.7%; P < .001) sites were more frequently used in ICU patients, whereas peripherally inserted (19.9% vs 5.9%; P < .001) and subclavian (60.7% vs 47.3%; P < .001) catheters were more commonly used in non-ICU patients. CONCLUSIONS Current surveillance and infection control efforts to reduce morbidity and mortality associated with bloodstream infections concentrate on the high-risk ICU patients with CVCs. Our survey demonstrated that two-thirds of identified CVCs were not in ICU patients and suggests that more efforts should be directed to patients with CVCs who are outside the ICU.

Microarray Transcription Analysis of Clinical Staphylococcus aureus Isolates Resistant to Vancomycin

The transcriptomes of vancomycin intermediate-resistance Staphylococcus aureus (VISA) clinical isolates HIP5827 and Mu50 (MIC = 8 micro g/ml) were compared to those of highly vancomycin-resistant S. aureus (VRSA; MIC = 32 micro g/ml) passage derivatives by microarray. There were 35 genes with increased transcription and 16 genes with decreased transcription in common between the two VRSAs compared to those of their VISA parents. Of the 35 genes with increased transcription, 15 involved purine biosynthesis or transport, and the regulator (purR) of the major purine biosynthetic operon (purE-purD) was mutant. We hypothesize that increased energy (ATP) is required to generate the thicker cell walls that characterize resistant mutants.

Legislative mandates for use of active surveillance cultures to screen for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: Position statement from the joint SHEA and APIC task force

Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association of Professionals in Infection Control and Epidemiology (APIC) have developed this joint position statement. Both organizations are dedicated to combating healthcare-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, APIC and SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) SHEA and APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) APIC and SHEA welcome efforts by healthcare consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and healthcare-associated infections. (4) SHEA and APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and cost-effectiveness of using active surveillance cultures to screen both lower-risk and high-risk populations. (5) APIC and SHEA support stronger collaboration between state and local public health authorities and institutional infection prevention and control experts.

Occurrence of Extended-Spectrum and AmpC Beta-Lactamases in Bloodstream Isolates of Klebsiella pneumoniae: Isolates Harbor Plasmid-Mediated FOX-5 and ACT-1 AmpC Beta-Lactamases

ABSTRACT We tested 190 Klebsiella pneumoniae bloodstream isolates recovered from 189 patients in 30 U.S. hospitals in 23 states to determine the occurrence of extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase producers. Based on growth inhibition by clavulanic acid by disk and MIC test methods, 18 (9.5%) of the isolates produced ESBLs. Although the disk diffusion method with standard breakpoints identified 28 cefoxitin-nonsusceptible isolates, only 5 (18%) of these were confirmed as AmpC producers. Of two AmpC confirmatory tests, the three-dimensional extract test was easier to perform than was the double-disk approximation test using a novel inhibitor, Syn2190. Three of the five AmpC producers carried the blaFOX-5 gene, while the other two isolates harbored the blaACT-1 gene. All AmpC genes were transferable. In vitro susceptibility testing with standard inocula showed that all five AmpC-producing strains were susceptible to cefepime, imipenem, and ertapenem but that with a high inoculum, more of these strains were susceptible to the carbapenems than to cefepime. All but 1 of 14 screen-positive AmpC nonproducers (and ESBL nonproducers) were susceptible to ceftriaxone and cefepime at the standard inoculum as were 6 of 6 isolates that were randomly selected and tested with a high inoculum. These results indicate that (i) a significant number of K. pneumoniae bloodstream isolates harbor ESBL or AmpC β-lactamases, (ii) confirmatory tests are necessary to identify true AmpC producers, and (iii) in vitro, carbapenems are active against AmpC-producing strains of K. pneumoniae.

Efficacy of Linezolid Alone or in Combination with Vancomycin for Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACT The levels of effectiveness of linezolid, vancomycin, and the combination of linezolid and vancomycin were compared in the rabbit model of endocarditis caused by a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate. Vancomycin alone was more effective than either linezolid alone or the combination of linezolid and vancomycin for the treatment of endocarditis due to MRSA.

Improved surveillance for surgical site infections after orthopedic implantation procedures: Extending applications for automated data

BACKGROUND Screening methods that use automated data may streamline surgical site infection (SSI) surveillance and improve the accuracy and comparability of data on SSIs. We evaluated the use of automated inpatient diagnosis codes and pharmacy data to identify SSIs after arthroplasty. METHODS This retrospective cohort study at 8 hospitals involved weighted, random samples of medical records from 2128 total hip arthroplasty (THA) procedures performed from 1 July 2002 through 30 June 2004, and 4194 total knee arthroplasty (TKA) procedures performed from 1 July 2003 through 30 June 2005. We compared routine surveillance with screening of inpatient pharmacy data and diagnoses codes followed by medical record review to confirm SSI status. RESULTS Records from 696 THA and 1009 TKA procedures were reviewed. The SSI rates were nearly double those determined by routine surveillance (1.32% [95% confidence interval, 0.83%-1.81%] vs. 0.75% for THA; 1.83% [95% confidence interval, 1.43%-2.23%] vs. 0.71% for TKA). An inpatient diagnosis code for infection within a year after the operation had substantially higher sensitivity (THA, 89%; TKA, 81%), compared with routine surveillance (THA, 56%; TKA, 39%). Adding antimicrobial exposure of 7 days after the procedure increased the sensitivity (THA, 93%; TKA, 86%). Record review confirmed SSIs after 51% of THAs and 55% of TKAs that met diagnosis code criteria and after 25% of THAs and 39% of TKAs that met antimicrobial exposure and/or diagnosis code criteria. CONCLUSIONS Focused surveillance among a subset of patients who met diagnosis code screening criteria with or without the addition of antimicrobial exposure-based screening was more sensitive than routine surveillance for detecting SSIs after arthroplasty and could be an efficient and readily standardized adjunct to traditional methods.