Extended spectrum β-lactamase producing enterobacteriaceae: carbapenem sparing options

ABSTRACT

Introduction: Carbapenems have an important place in our antibiotic armamentarium and have been trusted to effectively treat infections caused by ESBL-producing Enterobacteriaceae for many years. However, the utility of carbapenems has been compromised by the emergence of resistance especially in Enterobacteriaceae. Therefore, carbapenem-sparing alternative antibiotics are of extreme importance in clinical practice.

Areas covered: We reviewed studies addressing currently available antibiotic options used as both empiric and definitive therapy for the treatment of infections due to ESBL-producing Enterobacteriaceae published in the PubMed/MEDLINE, Web of Science and Scopus databases without any date restriction. Current treatment alternatives included beta-lactam/beta-lactamase inhibitor combinations, cefepime, cephamycins, fluoroquinolones, aminoglycosides, fosfomycin, pivmecillinam, temocillin and, various oral alternative agents. We also summarized the clinical and molecular epidemiology, early prediction methods and impact of initial empirical therapy and de-escalation approach for ESBL-producing Enterobacteriaceae infections.

Expert opinion: The current literature would endorse the carbapenem utilization for patients with severe and high inoculum-high risk infections. However, for milder infections particularly for urinary tract infections, various carbapenem-sparing antibiotics can be considered in selected cases. For infections including easily drainable intra-abdominal infections and catheter-related infections in which catheter removal is readily available more reliable data are needed to recommend non-carbapenem antibiotics confidently.

KEYWORDS:

• Extended-spectrum-beta-lactamases
• Beta-lactamase inhibitors
• carbapenems
• carbapenem-sparing options
• bloodstream infections

Article highlights

• Determining the appropriate empirical therapy for ESBL-producing Enterobacteriaceae infections is a great challenge in modern era.

• The utility of carbapenems has been compromised by the emergence of resistance especially in Enterobacteriaceae. Therefore, carbapenem-sparing alternative antibiotics are of extreme importance in clinical practice.

• Currently, available scientific evidence indicates that type-2 carbapenems remain the best alternatives for treating severe infections caused by ESBL-producing Enterobacteriaceae. However, this conclusion is mostly derived by observational studies and only one randomized, prospective trial with some limitations supported this suggestion.

• Alternatives to carbapenems in this setting include PTZ, fosfomycin and amikacin and they seem to be considered only for low risk-low inoculum infections such as UTIs.

• For infections including easily drainable intra-abdominal infections and catheter-related infections in which catheter removal is readily available more reliable data are needed to recommend non-carbapenem antibiotics confidently.

• Newer BLBLIs (ceftazidime-avibactam and ceftolozane-tazobactam) should be reserved only for infections with carbapenem-resistant organisms and resistant P. aeruginosa infections, respectively.

• Oral treatment alternatives merit further studies in community-onset infections caused by ESBL-producing Enterobacteriacea.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.