Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy

Abstract

Pseudomonas aeruginosa and Acinetobacter baumannii are major nosocomial pathogens worldwide. Both are intrinsically resistant to many drugs and are able to become resistant to virtually any antimicrobial agent. An increasing prevalence of infections caused by multidrug-resistant (MDR) isolates has been reported in many countries. The resistance mechanisms of P. aeruginosa and A. baumannii include the production of β-lactamases, efflux pumps, and target-site or outer membrane modifications. Resistance to multiple drugs is usually the result of the combination of different mechanisms in a single isolate or the action of a single potent resistance mechanism. There are many challenges in the treatment of MDR P. aeruginosa and A. baumannii, especially considering the absence of new antimicrobials in the drug-development pipeline. In this review, we present the major resistance mechanisms of P. aeruginosa and A. baumannii, and discuss how they can affect antimicrobial therapy, considering recent clinical, microbiological, pharmacokinetic and pharmacodynamic findings of the main drugs used to treat MDR isolates.

Keywords::

• β-lactamases
• carbapenems
• efflux pumps
• outer membrane protein
• polymyxins
• therapy
• tigecycline

Financial & competing interests disclosure

Alexandre Zavascki has received speaking honoraria from Forest Laboratories (UK). Ana Gales has received research funding, speaking grants, conference supporting and consulting fees from Janssen Cylag, Novartis, Sanofi-Aventis and Wyeth. Alexandre Zavascki and Ana Gales are research fellows of the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil (301829/2008-0 and 307714/2006-3, respectively). 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.

No writing assistance was utilized in the production of this manuscript.