Is there really no benefit to combination therapy with colistin?

Abstract

Evaluation of: Colistin and Rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized, clinical trial. Clin. Infect. Dis. 57(3), 349–358 (2013).

Despite many theoretical and in vitro advantages, clinical data comparing combination therapy with colistin + rifampicin to colistin alone for infection due to extremely-drug resistant (XDR) Acinetobacter baumanni are scarce and limited by small numbers and/or low quality evidence. This article represents the first large, randomized, controlled, prospective study comparing colistin monotherapy and combination therapy. The reviewed article found no difference in all cause or infection related mortality, though there was an improved rate of microbiological clearance in the combination therapy arm. This study adds important new data to the literature and sets the stage for future studies that can be designed to overcome the limitations of this study, which are discussed in detail below. Based on this study, we cannot say definitively that combination therapy is not warranted for treatment of invasive infection due to A. baumannii, but the results do suggest that rifampicin is not an ideal agent to be combined with colistin.

Keywords::

• Acinetobacter
• colistin
• colistimethate
• combination therapy
• Gram-negative
• polymyxin
• rifampin
• rifampicin
• resistance

Financial & competing interests disclosure

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.

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

Key issues

• • Mortality rates for life-threatening infections due to extensively drug-resistant Acinetobacter baumannii (XDR-AB) remain extremely high.

• • Colistin combination therapy remains an attractive option to overcome pharmacokinetic/pharmacodynamic limitations of colistin, heteroresistance to colistin and the narrow therapeutic index of the agent.

• • Data are still lacking regarding the optimal polymyxin and dosage; the role (if any) of combination therapy and which agents are best to combine with polymyxins; and strategies to minimize polymyxin-associated nephrotoxicity.