Bacteriology
Prevalence, mechanisms, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa

https://doi.org/10.1016/j.diagmicrobio.2007.05.006Get rights and content

Abstract

We examined the prevalence of various carbapenem resistance mechanisms in Pseudomonas aeruginosa bloodstream isolates from a university-affiliated hospital. Isolates obtained in 2003 and 2004 were screened for meropenem/imipenem resistance, and clonality was assessed by repetitive-element–based polymerase chain reaction. The presence of carbapenemase and AmpC overexpression was ascertained by spectrophotometric assays. Outer membrane protein profiles were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and efflux pump overexpression was confirmed by Western blotting. We examined 129 nonrepeat isolates; 21 isolates (from 13 distinct clones) were resistant to meropenem or imipenem (prevalence rate = 16.3%). Nineteen (90.5%) carbapenem-resistant isolates had reduced OprD expression, and 6 (28.6%) isolates had overexpression of MexB. Increased length of hospital stay was identified as a significant risk factor for bacteremia due to carbapenem-resistant P. aeruginosa. Understanding the prevalence and mechanism of carbapenem resistance in P. aeruginosa may guide empiric therapy for nosocomial infections in our hospital.

Introduction

Pseudomonas aeruginosa is an important pathogen associated with serious nosocomial infections. In 2003, P. aeruginosa was reported to be the most commonly isolated Gram-negative bacteria (18.1%) for nosocomial pneumonia and the second most commonly isolated Gram-negative bacteria (16.3%) for nosocomial urinary tract infection in the United States (Gaynes and Edwards, 2005). Treatment of infections due to P. aeruginosa can be difficult; bloodstream infections due to P. aeruginosa are especially detrimental and associated with mortality rates that range from 18% to 62% (Vidal et al., 1996).

Carbapenems are traditionally one of the last lines of agents that are used for difficult-to-manage pseudomonal infections. Carbapenem resistance in P. aeruginosa was reported to increase steadily over the years across the United States (Livermore, 2002, Gaynes and Edwards, 2005), but the relative contribution of different carbapenem resistance mechanisms is not well established. Consequently, the primary objective of the study was to determine the prevalence and mechanisms of carbapenem resistance in bloodstream isolates obtained from our institution. A secondary objective of the study was to identify risk factors associated with carbapenem resistance. It is anticipated that an improved understanding of the prevalence, mechanism, and risk factors of carbapenem resistance in P. aeruginosa may guide formulary decisions and the choice of empiric therapy for nosocomial infections in hospitals.

Section snippets

Study site

St. Luke's Episcopal Hospital is an 800-bed university-affiliated teaching hospital in Houston, TX. There are more than 120 intensive care unit beds in the hospital, and more than 100 open-heart surgeries are performed each month. This study was approved by the institutional review board of the hospital and the University of Houston, Houston, TX.

Bacteria and resistance screening

All nonrepeat (>7 days apart) bloodstream isolates of P. aeruginosa from 2003 and 2004 and their susceptibilities were obtained from the clinical

Bacteria, resistance screening, and genotyping

A total of 129 nonrepeat P. aeruginosa isolates were available, of which 21 (from 18 unique patients) were resistant to meropenem or imipenem (prevalence rate = 16.3%). All patients were hospitalized at least 48 h, and cross-resistance between meropenem and imipenem was found in 19 of 21 isolates. (Twenty isolates were resistant to meropenem and 20 isolates were resistant to imipenem.) In addition, cross-resistance to other antimicrobial agents was common: piperacillin/tazobactam (57%),

Discussion

P. aeruginosa is one of the most common pathogens implicated in serious nosocomial infections such as pneumonia and sepsis. Resistance to the commonly used agents has become more prevalent (Gales et al., 2002). If the rapid spread of antimicrobial resistance is unchecked, the serious threat to turn our era back to the preantibiotic age exists, wiping out the quantum leaps achieved a generation ago in the control of infectious diseases (Landman et al., 2002). Clearly, understanding the

Acknowledgments

The authors thank Stacie Frye, Ph.D. (Bacterial Barcodes) for technical assistance in interpreting the genotyping results. This study was supported in part by the Infectious Diseases Practice and Research Network, American College of Clinical Pharmacy Research Institute (Lenexa, KS) minisabbatical to V.H.T. K.P. is supported by the Canadian Cystic Fibrosis Foundation.

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