Clonal composition and community clustering of drug-susceptible and -resistant Escherichia coli isolates from bloodstream infections.

Multidrug-resistant Escherichia coli strains belonging to a single lineage frequently account for a large proportion of extraintestinal E. coli infections in many parts of the world. However, limited information exists on the community prevalence and clonal composition of drug-susceptible E. coli strains. Between July 2007 and September 2010, we analyzed all consecutively collected Gram-negative bacterial isolates from patients with bloodstream infection (BSI) admitted to a public hospital in San Francisco for drug susceptibility and associated drug resistance genes. The E. coli isolates were genotyped for fimH single nucleotide polymorphisms (SNPs) and multilocus sequence types (MLSTs). Among 539 isolates, E. coli accounted for 249 (46%); 74 (30%) of them were susceptible to all tested drugs, and 129 (52%) were multidrug resistant (MDR). Only five MLST genotypes accounted for two-thirds of the E. coli isolates; the most common were ST131 (23%) and ST95 (18%). Forty-seven (92%) of 51 ST131 isolates, as opposed to only 8 (20%) of 40 ST95 isolates, were MDR (P < 0.0001). The Simpson's diversity index for drug-susceptible ST genotypes was 87%, while the index for MDR ST genotypes was 81%. ST95 strains were comprised of four fimH types, and one of these (f-6) accounted for 67% of the 21 susceptible isolates (P < 0.003). A large proportion (>70%) of both MDR and susceptible E. coli BSI isolates represented community-onset infections. These observations show that factors other than the selective pressures of antimicrobial agents used in hospitals contribute to community-onset extraintestinal infections caused by clonal groups of E. coli regardless of their drug resistance.

Concurrent epidemics of skin and soft tissue infection and bloodstream infection due to community-associated methicillin-resistant Staphylococcus aureus.

BACKGROUND: Since its emergence in 2000, epidemic spread of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 has led to a high burden of skin and soft tissue infections (SSTIs) in the United States, yet its impact on MRSA bloodstream infections (BSIs) is poorly characterized. METHODS: To assess clonality of the MRSA isolates causing SSTI and BSI during the epidemic period, a stratified, random sample of 1350 unique infection isolates (from a total of 7252) recovered at the Community Health Network of San Francisco from 2000 to 2008 were selected for genotyping. Risk factors and outcomes for 549 BSI cases caused by the USA300 epidemic clone and non-USA300 MRSA clones were assessed by retrospective review of patient medical records. RESULTS: From 2000 to 2008, secular trends of USA300 SSTI and USA300 BSI were strongly correlated (Pearson r = 0.953). USA300 accounted for 55% (304/549) of BSIs as it was the predominant MRSA clone that caused community-associated (115/160), healthcare-associated community-onset (125/207), and hospital-onset (64/182) BSIs. Length of hospitalization after BSI diagnosis and mortality rates for USA300 and non-USA300 were similar. Two independent risk factors for USA300 BSI were identified: concurrent SSTI (adjusted relative risk, 1.4 [95% confidence interval {CI}, 1.2-1.6]) and anti-MRSA antimicrobial use in the preceding 30 days (0.7 [95% CI, .6-.8]). Isolates from concurrent SSTI were indistinguishable genotypically from the USA300 isolates that caused BSI. CONCLUSIONS: USA300 SSTIs serve as a source for BSI. Strategies to control the USA300 SSTI epidemic may lessen the severity of the concurrent USA300 BSI epidemic.

Methicillin-resistant Staphylococcus aureus USA300 clone in long-term care facility.

We performed a longitudinal analysis of 661 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients in a long-term care facility. USA300 clone increased from 11.3% of all MRSA isolates in 2002 to 64.0% in 2006 (p<0.0001) and was mostly recovered from skin or skin structures (64.3% vs. 27.0% for non-USA300 MRSA; p<0.0001).

Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men.

BACKGROUND: Infection with multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus (MRSA) has been reported but seems to be isolated. OBJECTIVE: To determine the incidence of a multidrug-resistant MRSA clone (USA300) in San Francisco, and to determine risk factors for the infection. DESIGN: Population-based survey and cross-sectional study using chart review. SETTING: 9 hospitals in San Francisco (population-based survey) and 2 outpatient clinics in San Francisco and Boston (cross-sectional study). PATIENTS: Persons with culture-proven MRSA infections in 2004 to 2006. MEASUREMENTS: Annual incidence, spatial clustering, and risk factors for multidrug-resistant USA300 infection. Pulsed-field gel electrophoresis, polymerase chain reaction assays, and DNA sequencing were used to characterize MRSA isolates. RESULTS: The overall incidence of multidrug-resistant USA300 infection in San Francisco was 26 cases per 100,000 persons (95% CI, 16 to 36 cases per 100,000 persons); the incidence was higher in 8 contiguous ZIP codes with a higher proportion of male same-sex couples. Male-male sex was a risk factor for multidrug-resistant USA300 infection (relative risk, 13.2 [CI, 1.7 to 101.6]; P < 0.001) independent of past MRSA infection (relative risk, 2.1 [CI, 1.2 to 3.7]; P = 0.007) or clindamycin use (relative risk, 2.1 [1.2 to 3.6]; P = 0.007). The risk seemed to be independent of HIV infection. In San Francisco, multidrug-resistant USA300 manifested most often as infection of the buttocks, genitals, or perineum. In Boston, the infection was recovered exclusively from men who had sex with men. LIMITATIONS: The study was retrospective, and sexual risk behavior was not assessed. CONCLUSION: Infection with multidrug-resistant USA300 MRSA is common among men who have sex with men, and multidrug-resistant MRSA infection might be sexually transmitted in this population. Further research is needed to determine whether existing efforts to control epidemics of other sexually transmitted infections can control spread of community-associated, multidrug-resistant MRSA.

A population-based study of the incidence and molecular epidemiology of methicillin-resistant Staphylococcus aureus disease in San Francisco, 2004-2005.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a major public health problem in both the community and hospitals. Few studies have characterized the incidence and clonal composition of disease-causing strains in an entire population. Our objective was to perform a population-based survey of the clinical and molecular epidemiology of MRSA disease in San Francisco, California. METHODS: We prospectively collected 3985 MRSA isolates and associated clinical and demographic information over a 12-month period (2004-2005) at 9 San Francisco-area medical centers. A random sample of 801 isolates was selected for molecular analysis. RESULTS: The annual incidence of community-onset MRSA disease among San Francisco residents was 316 cases per 100,000 population, compared with 31 cases per 100,000 population for hospital-onset disease. Persons who were aged 35-44 years, were men, and were black had the highest incidence of community-onset disease. The USA300 MRSA clone accounted for 234 cases of community-onset disease and 15 cases of hospital-onset disease per 100,000 population, constituting an estimated 78.5% and 43.4% of all cases of MRSA disease, respectively. Patients with community-onset USA300 MRSA versus non-USA300 MRSA disease were more likely to be male, be of younger age, and have skin and soft-tissue infections. USA300 strains were generally more susceptible to multiple antibiotics, although decreased susceptibility to tetracycline was observed in both community-onset (P = .008) and hospital-onset (P = .03) USA300 compared to non-USA300 strains. CONCLUSIONS: The annual incidence of community-onset MRSA disease in San Francisco is substantial, surpassing that of hospital-onset disease. USA300 is the predominant clone in both the community and hospitals. The dissemination of USA300 from the community into the hospital setting has blurred its distinction as a community-associated pathogen.

Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles.

BACKGROUND: Necrotizing fasciitis is a life-threatening infection requiring urgent surgical and medical therapy. Staphylococcus aureus has been a very uncommon cause of necrotizing fasciitis, but we have recently noted an alarming number of these infections caused by community-associated methicillin-resistant S. aureus (MRSA). METHODS: We reviewed the records of 843 patients whose wound cultures grew MRSA at our center from January 15, 2003, to April 15, 2004. Among this cohort, 14 were identified as patients presenting from the community with clinical and intraoperative findings of necrotizing fasciitis, necrotizing myositis, or both. RESULTS: The median age of the patients was 46 years (range, 28 to 68), and 71 percent were men. Coexisting conditions or risk factors included current or past injection-drug use (43 percent); previous MRSA infection, diabetes, and chronic hepatitis C (21 percent each); and cancer and human immunodeficiency virus infection or the acquired immunodeficiency syndrome (7 percent each). Four patients (29 percent) had no serious coexisting conditions or risk factors. All patients received combined medical and surgical therapy, and none died, but they had serious complications, including the need for reconstructive surgery and prolonged stay in the intensive care unit. Wound cultures were monomicrobial for MRSA in 86 percent, and 40 percent of patients (4 of 10) for whom blood cultures were obtained had positive results. All MRSA isolates were susceptible in vitro to clindamycin, trimethoprim-sulfamethoxazole, and rifampin. All recovered isolates belonged to the same genotype (multilocus sequence type ST8, pulsed-field type USA300, and staphylococcal cassette chromosome mec type IV [SCCmecIV]) and carried the Panton-Valentine leukocidin (pvl), lukD, and lukE genes, but no other toxin genes were detected. CONCLUSIONS: Necrotizing fasciitis caused by community-associated MRSA is an emerging clinical entity. In areas in which community-associated MRSA infection is endemic, empirical treatment of suspected necrotizing fasciitis should include antibiotics predictably active against this pathogen.

Long-term follow-up of methicillin-resistant Staphylococcus aureus molecular epidemiology after emergence of clone USA300 in San Francisco jail populations.

We performed a longitudinal analysis of 502 unique methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates originating from San Francisco jail inmates between 2000 and 2007. Strain USA300, first encountered in 2001, accounted for 82.1% (412/502) of MRSA infections. Non-USA300 MRSA strains were rarely found after 2005 (one isolate in 2006, three in 2007).

In vitro production of panton-valentine leukocidin among strains of methicillin-resistant Staphylococcus aureus causing diverse infections.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus strains have recently been associated with severe necrotizing infections. Greater than 75% of these strains carry the genes for Panton-Valentine leukocidin (PVL), suggesting that this toxin may mediate these severe infections. However, to date, studies have not provided evidence of toxin production. METHODS: Twenty-nine community-acquired methicillin-resistant Staphylococcus aureus and 2 community-acquired methicillin-susceptible S. aureus strains were collected from patients with infections of varying severity. Strains were analyzed for the presence of lukF-PV and SCCmecA type. PVL production in lukF-PV gene-positive strains was measured by ELISA, and the amount produced was analyzed relative to severity of infection. RESULTS: Only 2 of the 31 strains tested, 1 methicillin-resistant Staphylococcus aureus abscess isolate and 1 nasal carriage methicillin-susceptible S. aureus isolate, were lukF-PV negative. All methicillin-resistant Staphylococcus aureus strains were SCCmec type IV. PVL was produced by all strains harboring lukF-PV, although a marked strain-to-strain variation was observed. Twenty-six (90%) of 29 strains produced 50-350 ng/mL of PVL; the remaining strains produced PVL in excess of 500 ng/mL. The quantity of PVL produced in vitro did not correlate with severity of infection. CONCLUSIONS: Although PVL likely plays an important role in the pathogenesis of these infections, its mere presence is not solely responsible for the increased severity. Factors that up-regulate toxin synthesis in vivo could contribute to more-severe disease and worse outcomes in patients with community-acquired methicillin-resistant Staphylococcus aureus infection.

Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus.

BACKGROUND: USA300, a clone of meticillin-resistant Staphylococcus aureus, is a major source of community-acquired infections in the USA, Canada, and Europe. Our aim was to sequence its genome and compare it with those of other strains of S aureus to try to identify genes responsible for its distinctive epidemiological and virulence properties. METHODS: We ascertained the genome sequence of FPR3757, a multidrug resistant USA300 strain, by random shotgun sequencing, then compared it with the sequences of ten other staphylococcal strains. FINDINGS: Compared with closely related S aureus, we noted that almost all of the unique genes in USA300 clustered in novel allotypes of mobile genetic elements. Some of the unique genes are involved in pathogenesis, including Panton-Valentine leucocidin and molecular variants of enterotoxin Q and K. The most striking feature of the USA300 genome is the horizontal acquisition of a novel mobile genetic element that encodes an arginine deiminase pathway and an oligopeptide permease system that could contribute to growth and survival of USA300. We did not detect this element, termed arginine catabolic mobile element (ACME), in other S aureus strains. We noted a high prevalence of ACME in S epidermidis, suggesting not only that ACME transfers into USA300 from S epidermidis, but also that this element confers a selective advantage to this ubiquitous commensal of the human skin. INTERPRETATION: USA300 has acquired mobile genetic elements that encode resistance and virulence determinants that could enhance fitness and pathogenicity.

Ophthalmic manifestations of infections caused by the USA300 clone of community-associated methicillin-resistant Staphylococcus aureus.

PURPOSE: To report the microbiological, clinical, and pathological characteristics of community-associated methicillin-resistant Staphylococcus aureus (CAMRSA) infections of the eye and orbit. DESIGN: Prospective case series. PARTICIPANTS: Nine patients with CAMRSA infections of the eye and orbit were identified during a 6-month period at 2 tertiary care hospitals in San Francisco. METHODS: Case identification was by prospective case selection and retrospective laboratory review of 549 MRSA cultures collected in the 2 hospitals. Ophthalmic microbial isolates were analyzed by pulsed-field gel electrophoresis and compared with a control CAMRSA clone (USA300). Clinical characteristics of patients infected with CAMRSA were reviewed, and all surgical specimens underwent pathological examination. MAIN OUTCOME MEASURES: Pulsed-field gel electrophoresis banding patterns of MRSA isolates, antibiotic sensitivity profiles, patient demographics, systemic and ocular complications of infection, and posttreatment visual acuities. RESULTS: Nine ophthalmic isolates were CAMRSA clone USA300. The infections included orbital cellulitis, endogenous endophthalmitis, panophthalmitis, lid abscesses, and septic venous thrombosis. Patients were treated with trimethoprim-sulfamethoxazole, rifampin, clindamycin, or vancomycin based on microbial sensitivity studies and severity of infection. Eight of the 9 patients had no history of hospitalization. Seven patients required hospitalization, 3 required surgery, and an additional 4 required invasive procedures. Eight patients had good visual outcomes, but 1 deteriorated to no light perception. Pathological analyses showed extensive necrosis in eyelid and orbital specimens, and disorganized atrophy bulbi in an enucleated eye. CONCLUSION: The USA300 CAMRSA clone, which carries Panton-Valentine leukocidin genes, can cause aggressive infections of the eye and orbit in hospital-naive patients. Treatment of infections often required debridement of necrotic tissues in addition to non-beta-lactam class antibiotics. In communities where CAMRSA is prevalent, ophthalmologists should obtain microbial cultures and sensitivity studies to help guide antibiotic therapy for severe ophthalmic infections.

Community-associated methicillin-resistant Staphylococcus aureus necrotizing fasciitis in a neonate.

Neonatal necrotizing fasciitis is rare and is predominantly associated with methicillin-susceptible Staphylococcus aureus (MSSA). Necrotizing fasciitis associated with community-associated methicillin-resistant S aureus (CA-MRSA) has only recently been reported in the literature, primarily among adults. We present a case of a previously healthy neonate with necrotizing fasciitis of the back caused by CA-MRSA, pulsed-field type USA-300. We describe a 5-day-old infant with necrotizing fasciitis of the back caused by CA-MRSA. Treatment of necrotizing fasciitis requires prompt medical evaluation, prompt surgical debridement, and appropriate antibiotic selection. The potential involvement of CA-MRSA in necrotizing fasciitis in children needs to be considered before institution of antibiotics.

Fatal community-associated methicillin-resistant Staphylococcus aureus pneumonia in an immunocompetent young adult.

Severe pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) was reported in children soon after this pathogen emerged in the United States in the 1990s. Genes for Panton Valentine leukocidin, which are present in the majority of community-associated MRSA, are thought to enhance the ability of S aureus to cause necrotizing pneumonia. Despite the rapid spread throughout the United States of community-associated MRSA and related skin and soft-tissue infections, reports of severe pneumonia in adults have been rare. We describe a case of a healthy young adult who initially was treated as an outpatient with levofloxacin for what appeared to be typical community-acquired pneumonia. He soon returned to the emergency department (ED) with rapidly fatal necrotizing pneumonia, associated with hemoptysis, leukopenia, and sepsis syndrome, that was caused by community-associated MRSA carrying genes for Panton Valentine leukocidin. This case highlights the typical features of this form of pneumonia and the need to consider MRSA when evaluating and treating severe pneumonia in the ED. It also raises the question of whether the incidence of this form of pneumonia might be increasing in communities with a high prevalence of community-associated MRSA and whether current pneumonia treatment guidelines should be modified.

High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections.

STUDY OBJECTIVE: We sought to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among emergency department (ED) patients with skin and soft tissue infections, identify demographic and clinical variables associated with MRSA, and characterize MRSA by antimicrobial susceptibility and genotype. METHODS: This was a prospective observational study involving a convenience sample of patients who presented with skin and soft tissue infections to a single urban public hospital ED in California. Nares and infection site cultures were obtained. A health and lifestyle questionnaire was administered, and predictor variables independently associated with MRSA were determined by multivariate logistic regression. All S aureus isolates underwent antibiotic susceptibility testing. Eighty-five MRSA isolates underwent genotyping by pulsed field gel electrophoresis, staphylococcal chromosomal cassette mec (SCC mec ) typing, and testing for Panton-Valentine leukocidin genes. RESULTS: Of 137 subjects, 18% were homeless, 28% injected illicit drugs, 63% presented with a deep or superficial abscess, and 26% required admission for the infection. MRSA was present in 51% of infection site cultures. Of 119 S aureus isolates (from infection site and nares), 89 (75%) were MRSA. Antimicrobial susceptibility among MRSA isolates was trimethoprim/sulfamethoxazole 100%, clindamycin 94%, tetracycline 86%, and levofloxacin 57%. Among predictor variables independently associated with MRSA infection, the strongest was infection type being furuncle (odds ratio 28.6). Seventy-six percent of MRSA cases fit the clinical definition of community associated. Ninety-nine percent of MRSA isolates possessed the SCC mec IV allele (typical of community-associated MRSA), 94.1% possessed Panton-Valentine leukocidin genes, and 87.1% belonged to a single clonal group (ST8:S). CONCLUSION: In this urban ED population, MRSA is a major pathogen in skin and soft tissue infections. Although studies from other practice settings are needed, MRSA should be considered when empiric antibiotic therapy is selected for such infections.

Clostridial myonecrosis cluster among injection drug users: a molecular epidemiology investigation.

A molecular epidemiologic investigation was performed on a cluster of severe necrotizing Clostridium infections in 5 injection drug users admitted to an urban community hospital. Interviews with survivors suggested a point source of infection. Pulsed-field gel electrophoresis of SmaI restriction digests was performed to determine the molecular relatedness of clinically obtained isolates and isolates obtained from heroin samples and the home environment. A common clonal strain was found in Clostridium sordellii isolates from 2 socially unrelated patients and from drug paraphernalia. Clonality of a Clostridium perfringens strain from another patient isolate was identical to an isolate from a syringe found in her home. Other C perfringens isolates from patients, heroin, and the environment were determined to be polyclonal. We postulate that rapid recognition and public health notification led to rapid resolution of the outbreak.

Clinical, epidemiologic, and molecular evaluation of a clonal outbreak of methicillin-resistant Staphylococcus aureus infection.

San Francisco General Hospital (San Francisco, CA) experienced an overall increase in the recovery of methicillin-resistant Staphylococcus aureus (MRSA) isolates that were shown by pulsed-field gel electrophoresis to have a genotype (genotype A1) that was new to this institution. We performed a case-control study to identify risk factors for acquiring genotype A1 MRSA infection from 1 October 2001 to 19 July 2002. Patients with genotype A1 MRSA infection were compared with 2 control groups: MRSA-infected control patients (i.e., patients with infection due to non-genotype A1 MRSA) and non-MRSA infected control patients (i.e., hospitalized patients without MRSA infection). There were 41 case patients infected with genotype A1 MRSA, 99 control patients infected with MRSA, and 41 control patients without MRSA infection. Pneumonia, surgical wound infections, and line infections occurred more frequently among case patients. Intensive care unit exposure and invasive procedures conferred the greatest risk for genotype A1 MRSA infection in multivariate models. Case patients were not associated with increased mortality, after adjusting for age, comorbidities, and intensive care unit exposure. Genotype A1 MRSA caused a large nosocomial outbreak of infection that was associated with distinct risk factors and clinical manifestations.

Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails.

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.

Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco.

The study objective was to determine the prevalence and risk factors for nasal colonization with Staphylococcus aureus and methicillin resistance among the urban poor and to compare antibiotic resistance and genetic similarity to concurrently collected clinical isolates of methicillin-resistant S. aureus (MRSA). A population-based community sample of 833 homeless and marginally housed adults were cultured and compared with 363 clinical isolates of MRSA; 22.8% of the urban poor were colonized with S. aureus. Of S. aureus isolates, 12.0% were methicillin resistant. Overall prevalence of MRSA was 2.8%. Significant multivariate risk factors for MRSA were injection drug use (odds ratio [OR], 9.7), prior endocarditis (OR, 4.1), and prior hospitalization within 1 year (OR, 2.4). Resistance to antimicrobials other than beta-lactams was uncommon. Only 2 individuals (0.24%) with MRSA had no known risk factors. A total of 22 of 23 community MRSA genotypically matched clinical MRSA isolates, with 15 of 23 isolates identical to MRSA clones endemic among hospitalized patients.

Origins of community strains of methicillin-resistant Staphylococcus aureus.

To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community, we identified predictors of isolating community MRSA and genotyped a sample of MRSA collected from a community-based, high-risk population. Computerized databases of the Community Health Network of San Francisco and the Clinical Microbiology Laboratory were searched electronically for the years 1992-1999 to identify community-onset infections caused by MRSA. Sequential analyses were performed to identify predictors of MRSA strains. The majority (58%) of infections were caused by strains traceable to the hospital or to long-term care facilities. Injection drug use was associated with infections that were not associated with health care settings. Genotypes for 20 of 35 MRSA isolates recovered from injection drug users did not match any of >600 genotypes of clinical isolates. In a nonoutbreak setting, the hospital was the main source of community MRSA; however, the presence of genetically distinct and diverse MRSA strains indicates MRSA strains now also originate from the community.

Impact of a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam on colonization with vancomycin-resistant enterococci.

BACKGROUND: The prevalence of vancomycin-resistant enterococci (VRE) is increasing, despite infection control measures. Limited data link ticarcillin-clavulanate to higher VRE prevalence. METHODS: Active surveillance for VRE was conducted before and after a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult patients admitted to intensive care units (ICUs) between November 1, 2000 and September 30, 2004. RESULTS: In the postswitch period, 38 of 497 (7.6%) patients acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch ( P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006). Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide, nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10-month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch period. Infection control practices and use of other antibiotics remained stable. CONCLUSIONS: VRE acquisition appeared to decrease in association with a formulary change from ticarcillin-clavulanate to piperacillin-tazobactam.