Combination therapy for extensively-drug resistant gram-negative bacteria

ABSTRACT

Introduction: The ongoing crisis and emergence of extensively-drug resistant (XDR) gram-negative pathogens in the nosocomial setting is worrisome. The limited armamentarium in combination with the increasing resistance rates of last resort antibiotics has led clinicians to re-exploit existing antibiotic classes.

Areas covered: Current state of evidence concerning the administration of monotherapy versus combination therapy for the treatment of XDR gram-negative microorganism as well as salvage treatment are presented. Herein, the current knowledge concerning in vitro studies, animal models and clinical studies are discussed in detail.

Expert commentary: The efficacy of combination therapy in carbapenemase-producing K. pneumoniae is associated with reduced mortality in patients with septic shock and rapidly fatal underlying diseases. There is moderate evidence in support of the use of monotherapy for treating carbapenemase-producing Acinetobacter baumannii infections, however for septic shock patients, cancer patients and infections with an isolate with MIC in the upper limit of susceptibility combination therapy could be recommended. There are currently minimal and of low quality clinical evidence suggesting that combination treatment has no therapeutic advantage over monotherapy for XDR Pseudomonas aeruginosa infections. The in vivo validity of novel compounds and necessity for combination therapy is to be evaluated in future studies particularly for XDR infections.

KEYWORDS:

• XDR
• PDR
• combination
• monotherapy
• carbapenemase producing gram-negative
• Klebsiella pneumoniae
• Acinetobacter baumannii
• Pseudomonas aeruginosa
• double carbapenem combination
• colistin

Declaration of interest

H Giamarellou received research funding from Pfizer and MSD. A Antoniadou received funding from Gilead, honoraria and support for participation in congresses for Gilead, Bristol, Astellas, Pfizer and MSD. 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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The manuscript was not funded.