Noncarbapenems for the Treatment of Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Bacteria

C. Whitney White, PharmD, BCPS; Jeffrey A. Kyle, PharmD, BCPS; Crystal M. Deas, PharmD, BCPS; Jacob Campbell, PharmD

Disclosures

South Med J. 2019;112(8):438-443. 

In This Article

Abstract and Introduction

Abstract

Objectives: Urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are resistant to many conventional therapies, including third-generation cephalosporins. Carbapenems are considered first-line agents for ESBL infections, but their use is associated with increased multidrug resistance and should be reserved when absolutely necessary. Because of the increased rates of UTIs caused by ESBL-producing organisms and incidence of carbapenem resistance, safe and effective alternatives to carbapenems are needed. This study was conducted to evaluate the outcomes associated with the treatment of ESBL UTIs with noncarbapenem antibiotics.

Methods: A retrospective cohort study of adults with ESBL UTIs was conducted at a community hospital. Patients were categorized as those receiving definitive carbapenem therapy and those receiving definitive noncarbapenem therapy. Calculated measurements included infection-related mortality, length of hospital stay, and duration of definitive antibiotic therapy. Microbiological failure was assessed as a secondary outcome. Data on the safety of antibiotic therapy were not collected. P < 0.05 was considered significant.

Results: Fifty patients met inclusion criteria for the study, divided evenly between the two cohorts. No statistical differences were observed for length of hospital stay (P = 0.601), duration of therapy (P = 0.398), or rate of microbiological failure between the groups (P = 0.115).

Conclusions: Noncarbapenems did not demonstrate significant differences compared with carbapenems in the treatment of adults with ESBL UTIs. In certain patient populations, noncarbapenems that demonstrate in vitro activity may be appropriate for UTIs caused by ESBL-producing organisms.

Introduction

Extended-spectrum β-lactamases (ESBLs) are hydrolyzing enzymes produced by some Enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae, which confer resistance to most β-lactam antibiotics, including third-generation cephalosporins.[1] Since their discovery in the 1980s, infections caused by ESBL-producing organisms have increased in prevalence and have been associated with treatment failure and poor outcomes.[2] ESBL-producing organisms may cause a wide variety of infections, including pneumonia, wound infections, bacteremia, and intraabdominal infections, but they are most prevalent in urinary tract infections (UTIs). These UTIs include both healthcare-associated and, increasingly, community-acquired infections.[3–5]

By common definition, ESBLs are resistant to third-generation cephalosporins.[1,2] As such, they are resistant to some of the most commonly used agents for the treatment of UTIs, including ceftriaxone. In addition, ESBLs are often highly resistant to fluoroquinolones, aminoglycosides, and other antimicrobials used in UTIs, thus limiting treatment options.[6] Historically, carbapenems have been considered the antibiotics of choice for the treatment of ESBL infections because of their ability to resist hydrolysis by β-lactamases and their high rates of both in vitro activity and clinical success; however, the increasingly widespread use of carbapenems poses a number of concerns.[7] First, because of their broad spectrum of activity, carbapenems have been associated with an increase in multidrug-resistant infections. Second, some ESBL-producing Enterobacteriaceae are now able to produce carbapenemases, which render carbapenems ineffective, creating an urgent need for viable alternatives for ESBL infections should carbapenems fail.[8–10]

Concerns regarding multidrug resistance and emerging carbapenem-resistant ESBLs have led clinicians to explore other treatment options for ESBL infections, including UTIs.[11,12] A number of in vitro and in silico studies have examined the potential efficacy of noncarbapenem antibiotics in ESBL UTIs, and some have produced promising results. In vitro success does not necessarily translate to clinical success, however.[12–14] Several studies have assessed the clinical efficacy of noncarbapenems, but studies are still relatively few and most have been retrospective and observational in nature, while producing incomplete and sometimes conflicting results.[4,15–26]

As ESBL infections and widespread carbapenem use become increasing concerns, and because the existing literature yields incomplete conclusions, more studies are needed to evaluate the potential treatment of ESBL infections with noncarbapenem antibiotics. Data from a nonacademic setting may be useful to other similar institutions that lack resources such as a multidisciplinary antimicrobial stewardship team and oversight of an infectious diseases–trained pharmacist. The purpose of this study was to compare the efficacy of noncarbapenem therapy and carbapenem therapy in patients with UTIs caused by ESBL-producing bacteria in the setting of a community hospital.

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