Journal Article

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

Viscoli, Claudio, Malacarne, Paolo, Corcione, Antonio, De Cristoforo, Maria, Gallo, Ciro, Signoriello, Giuseppe, Bassetti, Matteo, Utili, Riccardo, Andini, Roberto, Mattei, Annunziata, Murino, Patrizia, Galdieri, Nicola, Mocavero, Paola, Zarrilli, Raffaele, Petrosillo, Nicola, Durante-Mangoni, Emanuele

2013

Overview

Background. Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. Methods. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. Results. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46–1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. Conclusions. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. Clinical Trials Registration. NCT01577862.

• Publisher: Oxford University Press
• Subject: Acinetobacter / Acinetobacter baumannii / Acinetobacter baumannii - drug effects / Acinetobacter baumannii - isolation & purification / Acinetobacter Infections - drug therapy / Acinetobacter Infections - mortality / Adult / Aged / Aged, 80 and over / Anti-Bacterial Agents - therapeutic use / Antibacterial agents / Antibiotics. Antiinfectious agents. Antiparasitic agents / Arm / ARTICLES AND COMMENTARIES / Bacterial infections / Biological and medical sciences / Clinical trials / Colistin - therapeutic use / Critical Illness / Dosage / Drug resistance / Drug Resistance, Multiple, Bacterial / Drug Therapy, Combination - methods / Female / Health outcomes / Hospitalization / Hospitals / Humans / Infections / Infectious diseases / Intensive care / Intensive Care Units / Length of Stay / Male / Medical sciences / Microbial sensitivity tests / Middle Aged / Mortality / Multivariate analysis / Patients / Pharmacology. Drug treatments / Rifampin - therapeutic use / Survival Analysis / Tertiary Care Centers / Treatment Outcome