Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options.

Yoav Golan

doi:10.1186/s12879-015-1054-1

Abstract

BackgroundEmpiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug–resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam.MethodsThis systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa.ResultsClinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded.ConclusionsPractitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.

Highlights

Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug–resistant organisms
The purpose of this review is to provide an overview of the clinical trial evidence supporting these established and emerging options for empiric therapy in patients with healthcare-associated complicated intraabdominal infections [complicated intra-abdominal infection (cIAI)] or healthcare-associated complicated urinary tract infections [cUTIs] in which treatment must account for the risk of Extended-spectrum βlactamase (ESBL)
Complicated intra-abdominal infection Among the indications included in this overview, cIAI had the largest set of high- and medium-quality supporting trials

Summary

Introduction

Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug–resistant organisms. The increasing prevalence of bacterial infections with resistance to currently available antibiotics and the limited number of new antibiotics in development are welldocumented [1, 2] This issue is especially acute for Gram-negative, healthcare-associated infections (HAIs), prompting the U.S Centers for Disease Control and Prevention (CDC) to issue warnings regarding Gramnegative organisms, highlighting both the ability of these organisms to develop drug resistance and the scarcity of new treatments to combat them [3]. Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria tend to harbor resistance to several classes of non–β-lactam antibiotics, including fluoroquinolones, aminoglycosides, and trimethoprim-sulfamethoxazole [6]. As a consequence, these classes of antibiotics are generally associated with worse outcomes when treatment needs to account for the possibility of an ESBLproducing strain [7,8,9,10]. Recent clinical trials have supported the use of novel or third-generation cephalosporins in combination with a β-lactamase inhibitor in this setting

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