Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system.

Retrospective cohort study.

All patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT).

A total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16–15.82; P<.01). Other independent risk factors for clinical failure included infection with Citrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64–7.33; P<.01).

Community-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.

To describe the pattern of blood culture utilization in an academic university hospital setting.

Retrospective cohort study.

A 789-bed tertiary-care university hospital that processes 40,000+blood cultures annually.

We analyzed blood cultures collected from adult inpatients at the Hospital of the University of Pennsylvania between July 1, 2014, and June 30, 2015. Descriptive statistics and regression models were used to analyze patterns of blood culture utilization: frequency of blood cultures, use of repeat cultures following a true-positive culture, and number of sets drawn per day.

In total, 38,939 blood culture sets were drawn during 126,537 patient days (incidence rate, 307.7 sets per 1,000 patient days). The median number of blood culture sets drawn per hospital encounter was 2 (range, 1–76 sets). The median interval between blood cultures was 2 days (range, 1–71 days). Oncology services and cultures with gram-positive cocci were significantly associated with greater odds of having repeat blood cultures drawn the following day. Emergency services had the highest rate of drawing single blood-culture sets (16.9%), while oncology services had the highest frequency of drawing ≥5 blood culture sets within 24 hours (0.91%). Approximately 10% of encounters had at least 1 true-positive culture, and 89.2% of those encounters had repeat blood cultures drawn. The relative risk of a patient having repeat blood cultures was lower for those in emergency, surgery, and oncology services than for those in general medicine.

Ordering practices differed by service and culture results. Analyzing blood culture utilization can contribute to the development of guidelines and benchmarks for appropriate usage.

To evaluate risk factors for and molecular characteristics of community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) urinary tract infections (UTIs) in a US health system.

Case-control study.

All patients presenting to the emergency department or outpatient practices with EB UTIs from December 21, 2010, through April 22, 2013, were included. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched 1:1 on study year.

Risk factors for ESC-R EB UTI were assessed using multivariable conditional logistic regression. A subset of case isolates was evaluated for extended-spectrum beta-lactamases.

A total of 302 patients with community-onset EB UTI were included, of which 151 were cases. On multivariable analysis, risk factors for ESC-R EB UTI included trimethoprim-sulfamethoxazole use in the prior 6 months (odds ratio, 2.40 [95% CI, 1.22–4.70]; P=.01), older age (1.03 [1.01–1.04]; P<.001), diabetes (2.91 [1.32–6.41]; P=.008), and presentation to the emergency department ( 2.42 [1.31–4.46]; P=.005). The prevalence of extended-spectrum beta-lactamases among 120 case isolates was 52% CTX-M, 29% TEM, 20% OXA, and 13% SHV. The prevalence of AmpC was 25%. Pulsed-field gel electrophoresis of the CTX-M Escherichia coli isolates showed no distinct clusters.

Use of trimethoprim-sulfamethoxazole, older age, diabetes, and presentation to the emergency department were associated with community-onset ESC-R EB UTI. There was a high prevalence of CTX-M among our community isolates. Further studies are needed to determine strategies to limit emergence of these organisms in the community.

Infect Control Hosp Epidemiol 2016;1433–1439

To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.

Three-arm nonmasked randomized controlled trial.

Five academic medical centers in Southeastern Pennsylvania.

Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.

Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.

Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.

Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).

Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance

Trial registration. ClinicalTrials.gov identifier: NCT00966446

Infect Control Hosp Epidemiol 2016;1–8

To identify risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization.

Prospective cohort study conducted from January 1, 2010, through December 31, 2012.

Five adult and pediatric academic medical centers.

Subjects (ie, index cases) who presented with acute community-onset MRSA skin and soft-tissue infection.

Index cases and all household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as 2 consecutive sampling periods with negative surveillance cultures. Recurrent colonization was defined as any positive MRSA surveillance culture after clearance. Index cases with recurrent MRSA colonization were compared with those without recurrence on the basis of antibiotic exposure, household demographic characteristics, and presence of MRSA colonization in household members.

The study cohort comprised 195 index cases; recurrent MRSA colonization occurred in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36–84 days). Treatment with clindamycin was associated with lower risk of recurrence (odds ratio, 0.52; 95% CI, 0.29–0.93). Higher percentage of household members younger than 18 was associated with increased risk of recurrence (odds ratio, 1.01; 95% CI, 1.00–1.02). The association between MRSA colonization in household members and recurrent colonization in index cases did not reach statistical significance in primary analyses.

A large proportion of patients initially presenting with MRSA skin and soft-tissue infection will have recurrent colonization after clearance. The reduced rate of recurrent colonization associated with clindamycin may indicate a unique role for this antibiotic in the treatment of such infection.

Infect. Control Hosp. Epidemiol. 2015;36(7):786–793

The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations.

Case-case-control study

Two adult academic acute-care hospitals

Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more.

Each case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared.

Of 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04–1.13; OR, 1.14; 95% CI, 1.03–1.26; case 2 OR, 1.09; 95% CI, 1.03–1.14; OR, 1.13; 95% CI, 1.01–1.25, respectively).

Exposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.

Infect Control Hosp Epidemiol 2015;00(0): 1–7

Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization.

A prospective cohort study was conducted from 2002 to 2004 within a university health system.

Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates.

Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1–1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21–0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10–1.29]; P<.001) or cefepime (HR, 1.05 [95% CI, 1.00–1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization.

The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

Comparison of studies evaluating patient-to-patient transmission of organisms is difficult, given the lack of standardized criteria. We used fluoroquinolone-resistant Escherichia coli (FQREC) as a model to characterize variability in definitions of relatedness across studies and to evaluate the resultant impact on study conclusions.

Narrative review and cohort study.

The narrative review compared relatedness criteria across studies of FQREC. Additionally, an existing database was used to compare relatedness of isolates on the basis of molecular criteria alone versus molecular plus clinical criteria with different temporal cutoffs (hospitalization overlap of ≥1 day or allowance for nonoverlap of hospitalization dates of ≤7 days or ≤30 days).

Forty-six articles met narrative review inclusion criteria. Sixteen studies exclusively utilized molecular criteria to define relatedness. Thirty studies included molecular and clinical criteria. Of these, 6 included temporal data (ie, time period of isolate identification), 10 included patient location, and 14 included proximity and temporal criteria. For the database analysis, 353 patients were colonized with FQREC. There were 2 main clusters containing 48 and 17 related isolates within 49 pulsed-field gel electrophoresis types. Among the clusters, 18.4% of isolates were related by molecular criteria. Incorporating clinical criteria, fewer isolates were considered related: 5.7% of isolates using 30-day criteria, 3.1% using 7-day criteria, and 1.4% using 1-day overlap.

There is considerable variability in definitions of relatedness of FQREC. Utilizing molecular criteria alone to define relatedness overestimates transmission compared with definitions including clinical criteria. Standard definitions of relatedness in studies of antimicrobial-resistant organisms are needed.

The prevalence of fluoroquinolone (FQ) resistance in Escherichia coli has increased markedly in recent years. Despite the important role of gastrointestinal tract colonization with FQ-resistant E. coli (FQREC), the prevalence of and risk factors for FQREC colonization among the general hospitalized patient population have not been described, to our knowledge. The objective of this study was to identify the prevalence of and risk factors for FQREC colonization among hospitalized patients.

Three-year case-control study. Case patients (ie, all subjects with FQREC colonization) were compared with control patients (ie, all subjects without FQREC colonization).

Two large medical centers within an academic health system.

All patients hospitalized at the 2 study hospitals.

Three annual fecal surveillance surveys were conducted. All patients colonized with FQREC (levofloxacin minimum inhibitory concentration, ≥ 8 μg/mL) were identified.

Of the 774 subjects, 89 (11.5%) were colonized with FQREC. Although there was a significant association between prior FQ use and FQREC colonization on bivariable analysis (odds ratio [OR], 2.02 [95% confidence interval {CI}, 1.14–3.46]; P = .01), there was statistically significant effect modification by year of study (P = .005). In multivariable analyses, after controlling for the hospital and for the duration of hospitalization prior to sampling, the association between FQ use and FQREC colonization was as follows: adjusted OR (aOR), 0.97 (95% CI, 0.29–3.23) in 2002; aOR, 1.41 (95% CI, 0.57–3.50) in 2003; and aOR, 9.87 (95% CI, 3.67–26.55) in 2004.

The association between prior FQ use and FQREC colonization varied significantly by study year, suggesting that the clinical epidemiology of resistant organisms may change over time. Furthermore, in the context of recent work showing significant changes in FQREC prevalence as well as changes in FQ resistance mechanisms (specifically, efflux overexpression) over the same time period, these results suggest a previously unrecognized complexity in the relationship between the clinical and molecular epidemiology of FQ resistance.

To identify risk factors for infection or colonization with aztreonam-resistant Pseudomonas aeruginosa and examine the impact of this organism on mortality.

A case-control study was performed to identify risk factors for infection or colonization with aztreonam-resistant P. aeruginosa. A cohort study was subsequently performed to examine the impact of aztreonam resistance on outcomes.

A tertiary referral center in southeastern Pennsylvania.

Inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.

Of 720 P. aeruginosa, isolates, 183 (25.4%) were aztreonam-resistant and 537 (74.6%) were aztreonam susceptible. In a multivariable model, prior fluoroquinolone use (adjusted odds ratio [aOR], 1.81 [95% confidence interval {CI}, 1.17-2.80]), prior use of an antianaerobic agent (aOR, 1.56 [95% CI, 1.06-2.29]), and renal insufficiency (aOR, 1.59 [95% CI, 1.10-2.29]) were associated with infection or colonization with aztreonam-resistant P. aeruginosa, while older age (aOR, 0.98 [95% CI, 0.97-0.99] per year of age) was negatively associated with infection or colonization with this organism. In-hospital mortality was higher among subjects infected or colonized with aztreonam-resistant P. aeruginosa, compared with those who were infected or colonized with aztreonam-susceptible P. aeruginos (25.7% vs 16.8%;P = .009), but in multivariable analysis, no significant association was found between infection or colonization with aztreonam-resistant P. aeruginosa and mortality.

Curbing the use of fluoroquinolones and antimicrobials with antianaerobic activity may be an effective strategy to limit the emergence of aztreonam-resistant P. aeruginosa.

To identify risk factors for infection with imipenem-resistant Pseudomonas aeruginosa and determine the impact of imipenem resistance on clinical and economic outcomes among patients infected with P. aeruginosa.

An ecologic study, a case-control study, and a retrospective cohort study.

A 625-bed tertiary care medical center.

All patients who had an inpatient clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.

From 1991 through 2000, the annual prevalence of imipenem resistance among P. aeruginosa isolates increased significantly (P<.001 by the χ2 test for trend). Among 879 patients infected with P. aeruginosa during 1999-2000, a total of 142 had imipenem-resistant P. aeruginosa infection (the case group), whereas 737 had imipenem-susceptible P. aeruginosa infection (the control group). The only independent risk factor for imipenem-resistant P. aeruginosa infection was prior fluoroquinolone use (adjusted odds ratio, 2.52 [95% confidence interval {CI}, 1.61-3.92]; P<.001). Compared with patients infected with imipenem-susceptible P. aeruginosa, patients infected with imipenem-resistant P. aeruginosa had longer subsequent hospitalization durations (15.5 days vs 9 days; P = .02) and greater hospital costs ($81,330 vs $48,381; P<.001). The mortality rate among patients infected with imipenem-resistant P. aeruginosa was 31.1%, compared with 16.7% for patients infected with imipenem-susceptible P. aeruginosa (relative risk, 1.86 [95% CI, 1.38-2.51]; P<.001). In multivariable analyses, there remained an independent association between infection with imipenem-resistant P. aeruginosa and mortality.

The prevalence of imipenem resistance among P. aeruginosa strains has increased markedly in recent years and has had a significant impact on both clinical and economic outcomes. Our results suggest that curtailing use of other antibiotics (particularly fluoroquinolones) may be important in attempts to curb further emergence of imipenem resistance.

To identify differences between unit-specific and hospital-wide antibiograms and to determine the potential impact of these differences on selection of empirical antimicrobial therapy.

A 625-bed tertiary care medical center.

Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram.

A total of 9,970 bacterial isolates were evaluated in this study, including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates resistant to antimicrobials were significantly higher in the medical ICU and surgical ICU than the hospital-wide antibiogram would have predicted, whereas the percentages of isolates susceptible to antimicrobials were significantly higher in the non-ICU units, compared with the hospital overall. However, on general medicine units, the prevalence of susceptibility to levofloxacin was significantly lower than that for the hospital overall.

Unit-specific antibiograms are important for making informed decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram may mask important differences in susceptibility rates across different units. These differences may have important implications for selecting the optimal empirical antimicrobial therapy.

To identify differences between unit-specific and hospital-wide antibiograms and to determine the potential impact of these differences on selection of empirical antimicrobial therapy.

A 625-bed tertiary care medical center.

Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram.

A total of 9,970 bacterial isolates were evaluated in this study, including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates resistant to antimicrobials were significantly higher in the medical ICU and surgical ICU than the hospital-wide antibiogram would have predicted, whereas the percentages of isolates susceptible to antimicrobials were significantly higher in the non-ICU units, compared with the hospital overall. However, on general medicine units, the prevalence of susceptibility to levofloxacin was significantly lower than that for the hospital overall.

Unit-specific antibiograms are important for making informed decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram may mask important differences in susceptibility rates across different units. These differences may have important implications for selecting the optimal empirical antimicrobial therapy.

Effective methods to control the emergence of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions.

To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included.

After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P< .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]).

The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

The prevalence of vancomycin-resistant enterococci (VRE) has increased markedly during the past decade. Few data exist regarding the epidemiology of resistance of VRE to chloramphenicol, one of the few therapeutic options.

Survey and case-control study.

A 725-bed, tertiary-care academie medical center and a 344-bed urban community hospital.

Hospitalized patients with blood cultures demonstrating VRE.

We examined the trends in the prevalence of chloramphenicol resistance in VRE blood isolates at our institution from 1991 through 2002 and conducted a case-control study to identify risk factors for chloramphenicol resistance among these isolates.

From 1991 through 2002, the annual prevalence of chloramphenicol-resistant VRE increased from 0% to 12% (P < .001, chi-square test for trend). Twenty-two case-patients with chloramphenicol-resistant VRE bloodstream isolates were compared with 79 randomly selected control-patients with chloramphenicol-susceptible VRE. Independent risk factors for chloramphenicol-resistant VRE were prior chloramphenicol use (odds ratio [OR], 10.9; 95% confidence interval [CI95], 1.72-68.91; P = .01) and prior fluoroquinolone use (OR, 4.74; CI95, 1.15-19.42; P = .03). Chloramphenicol-resistant VRE isolates were more likely to be susceptible to beta-lactams and resistant to tetracycline than were chloramphenicol-susceptible VRE isolates.

Significant increases in the prevalence of chloramphenicol-resistant VRE may limit the future utility of chloramphenicol in the treatment of VRE infections, and close monitoring of susceptibility trends should continue. The association between fluoroquinolone use and chloramphenicol-resistant VRE, reflecting possible co-selection of resistance, suggests that recent dramatic increases in fluoroquinolone use may have broader implications than previously recognized.