Use of meropenem in treating carbapenem-resistant Enterobacteriaceae infections

ABSTRACT

Introduction: The epidemiology of carbapenem-resistant Enterobacterales (CRE) is increasingly worldwide. Production of carbapenemases is the most common and efficient mechanism of carbapenem resistance, and could theoretically be overcome by optimizing the pharmacokinetic/pharmacodynamic (PK/PD) behavior of meropenem.

Areas covered: This article overviews the available literature concerning the potential role that meropenem may still have in the treatment carbapenem-resistant Enterobacteriaceae infections. Clinical studies published in English language until June 2019 were searched on PubMed database.

Expert commentary: High-dose continuous infusion meropenem-based combination regimens could still represent a valuable option for treating CRE infections in specific circumstances. Knowledge of the local prevalent mechanisms of carbapenem resistance, of patient clinical severity, of the site of infection, of an accurate minimum inhibitory concentration (MIC) value, coupled with the possibility of carrying-out a real-time therapeutic drug monitoring (TDM)-based PK/PD optimization of drug exposure must all be considered as fundamental for properly pursuing this goal.

KEYWORDS:

• Meropenem
• Combination therapy
• continuous infusion
• PK/PD optimization
• CRE treatment
• therapeutic drug monitoring

Article highlights

• Meropenem-based combinations could be considered for the treatment of CRE infections in specific circumstances. The partner drug should be chosen according to the in vitro activity, the infection site, and the PK/PD properties.

• Administration of high-dose meropenem by extended/continuous infusion is mandatory to increase the antibacterial activity and to counteract resistance development during therapy.

• TDM could be a valuable tool in improving PK/PD optimization of meropenem in a combination regimen for the treatment of CRE infections.

• Current clinical and pharmacological data support the safety of high dose extended/continuous infusion therapy with meropenem.

Declaration of interest

F Pea participated in speaker bureau for Angelini, Basilea Pharmaceutica, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Pfizer, and Sanofi Aventis, and in advisory board for Angelini, Basilea Pharmaceutica, Correvio, Gilead, Merck Sharp & Dohme, Nordic Pharma, Novartis, Pfizer, and Thermo-Fisher. P Viale has served as a consultant for Biomerieux, Gilead, Merck Sharp & Dohme, Nabriva, Pfizer, Thermo-Fisher, and Venatorx, and received payment for serving on the speaker’s bureau for Correvio, Gilead, Merck Sharp & Dohme, and Pfizer. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.