Lori A. Larosa

Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins.

This study sought to assess the impact of restricting use of vancomycin and third-generation cephalosporins on vancomycin-resistant enterococci (VRE) prevalence. All clinical enterococcal isolates identified at a large academic medical center during a 10-year period were analyzed. Changes in VRE prevalence after sequential restrictions on use of vancomycin and third-generation cephalosporins were evaluated. The correlation between antibiotic use and VRE prevalence was also investigated. Vancomycin use initially decreased by 23.9% but returned to preintervention levels by the end of the study. Third-generation cephalosporin use decreased by 85.8%. However, VRE prevalence increased steadily from 17.4% to 29.6% during the 10-year period (P<.001). Clindamycin use was significantly correlated with VRE prevalence. Restricting the use of vancomycin and third-generations cephalosporins had little impact on VRE prevalence. The association between clindamycin use and the prevalence of VRE suggests that restriction of this and perhaps other antianaerobic agents might be an important component of future antimicrobial interventions.

Longitudinal Trends in Fluoroquinolone Resistance among Enterobacteriaceae Isolates from Inpatients and Outpatients, 1989–2000: Differences in the Emergence and Epidemiology of Resistance across Organisms

We conducted a 12-year study to identify and compare trends in annual prevalence of fluoroquinolone (FQ) resistance among Enterobacteriaceae isolates obtained from inpatients and outpatients in our health care system. A total of 46,070 clinical Enterobacteriaceae isolates underwent susceptibility testing. Although there were significant increases in inpatient FQ resistance for all Enterobacteriaceae, FQ resistance trends differed significantly across Enterobacteriaceae (P<.001). For isolates obtained from outpatients, only Escherichia coli and Proteus mirabilis demonstrated significant increases in FQ resistance (P<.001 for each). Trends in outpatient FQ resistance also differed significantly across Enterobacteriaceae (P<.001). There were significant differences between inpatient and outpatient FQ resistance trends for all Enterobacteriaceae except P. mirabilis and Enterobacter cloacae. Although hospital-wide use of certain antibiotics correlated significantly with inpatient FQ resistance, these correlations differed substantially across organisms. Efforts to elucidate the epidemiology of FQ resistance and identify targets for intervention must recognize and account for the variability of FQ resistance across organisms and clinical settings.

Comparison of unit-specific and hospital-wide antibiograms: potential implications for selection of empirical antimicrobial therapy.

OBJECTIVE 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. SETTING A 625-bed tertiary care medical center. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Limiting the Emergence of Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceae: Influence of Patient Population Characteristics on the Response to Antimicrobial Formulary Interventions

BACKGROUND Effective methods to control the emergence of extended-spectrum beta -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. METHODS 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. RESULTS 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]). CONCLUSIONS 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.

Evaluation of Antimicrobial Therapy Orders Circumventing an Antimicrobial Stewardship Program: Investigating the Strategy of “Stealth Dosing”

OBJECTIVE Prior-approval antimicrobial stewardship programs (ASPs) improve patient outcomes and decrease antimicrobial resistance. These benefits would be limited if physicians circumvented ASP efforts. We evaluated whether prescribers wait until after the prior-approval period to order restricted antimicrobial therapy that is in conflict with guidelines or unnecessary. DESIGN A cross-sectional study design and a retrospective cohort study design. SETTING A tertiary care, academic medical center with a prior-approval ASP that was active between 8 am and 10 pm. METHODS We evaluated whether there was an increase in the proportion of orders for antimicrobial therapy that involve restricted (vs nonrestricted) antimicrobials during the first hour that the ASP is inactive (ie, the first hour that prior approval is not required), compared with the remainder of the day. We also evaluated whether restricted antimicrobial therapy ordered during this first hour is less likely to be continued when the ASP becomes active the next day, compared with that ordered during the preceding hour. RESULTS A greater proportion of the antimicrobial therapy orders placed between 10:00 pm and 10:59 pm were for restricted agents, compared with orders placed during other periods (57.0% vs 49.9%; P=.02). Surgical patients for whom antimicrobial therapy orders were placed between 10:00 pm and 10:59 pm were less likely to have that antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 pm and 9:59 pm (60.0% vs 98.1%; P<.001). Nonsurgical patients whose therapy orders were placed between 10:00 pm and 10:59 pm were also less likely to have the ordered antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 pm and 9:59 pm (70.8% vs 84.2%; P=.01). CONCLUSION Physicians avoid having to obtain prior approval for therapy involving restricted antimicrobials by waiting until restrictions are no longer active to place orders. Compared with restricted antimicrobial therapy ordered when the ASP is active, these courses of therapy are less often continued by the ASP, suggesting that they are more likely to be in conflict with guidelines or unnecessary.

High rate of coadministration of di- or tri-valent cation-containing compounds with oral fluoroquinolones: Risk factors and potential implications

BACKGROUND The characteristics of fluoroquinolone use that increase the risk of selecting for fluoroquinolone resistance remain unclear. Exposure to subtherapeutic levels of fluoroquinolone promotes bacterial development of fluoroquinolone resistance. Oral fluoroquinolone absorption is significantly impaired by coadministration with many common di- or tri-valent cation-containing compounds (DTCCs), and this interaction has been associated with therapeutic failure. However, the prevalence of, and risk factors for, in-hospital coadministration of oral fluoroquinolones with DTCCs is unknown. DESIGN Case-control study. SETTING A 625-bed, tertiary-care medical center. PATIENTS All inpatients who were dispensed oral levofloxacin from July 1, 1999, to June 30, 2001, were included. Coadministration was defined by documented administration of any DTCC within 2 hours of levofloxacin. Complete coadministration was defined as coadministration complicating every dose of a course of levofloxacin. RESULTS A subset of 3,227 (41.0%) of 7,871 doses of levofloxacin that occurred during the same calendar day as any DTCC was selected for further review. Overall, 1,904 (77.1%) of 2,470 doses of oral levofloxacin reviewed were complicated by coadministration with at least one DTCC. On multivariable analysis, an increased number of prescribed medications was significantly associated with complete coadministration (per increase of one medication: OR, 1.05; CI95, 1.01-1.10; P = .036), whereas patient location in an ICU was protective (OR, 0.51; CI95, 0.30-0.87; P = .013). If our prevalence results are extrapolated to all patients receiving oral levofloxacin at our hospital, approximately one in three doses was complicated by coadministration. CONCLUSION Coadministration of fluoroquinolones with DTCCs is extremely common and significantly associated with polypharmacy.