Treatment Outcomes of Colistin- and Carbapenem-resistant Acinetobacter baumannii Infections: An Exploratory Subgroup Analysis of a Randomized Clinical Trial
Authors: Dickstein Yaakov , Lellouche Jonathan , Ben Dalak Amar Maayan , Schwartz David , Nutman Amir , Daitch Vered , Yahav Dafna , Leibovici Leonard , Skiada Anna , Antoniadou Anastasia , Daikos George L , Andini Roberto , Zampino Rosa , Durante-Mangoni Emanuele , Mouton Johan W , Friberg Lena E , Dishon Benattar Yael , Bitterman Roni , Neuberger Ami , Carmeli Yehuda , Paul Mical ,   AIDA Study Group, Paul Mical , Dishon Benattar Yael , Dickstein Yaakov , Bitterman Roni , Zayyad Hiba , Koppel Fidi , Zak-Doron Yael , Altunin Sergey , Andria Nizar , Neuberger Ami , Stern Anat , Petersiel Neta , Raines Marina , Karban Amir , Leibovici Leonard , Yahav Dafna , Eliakim-Raz Noa , Zusman Oren , Elbaz Michal , Atamna Heyam , Daitch Vered , Babich Tanya , Carmeli Yehuda , Nutman Amir , Adler Amos , Levi Inbar , Daikos George L , Skiada Anna , Pavleas Ioannis , Antoniadou Anastasia , Kotsaki Antigoni , Durante-Mangoni Emanuele , Andini Roberto , Iossa Domenico , Bernardo Mariano , Cavezza Giusi , Bertolino Lorenzo , Giuffre Giuseppe , Giurazza Roberto , Cuccurullo Susanna , Galdo Maria , Murino Patrizia , Cristinziano Adriano , Corcione Antonio , Zampino Rosa , Clara Pafundi Pia 
Published: November 2018

Abstract

Background
We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy.

Methods
This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality.

Results
Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]).

Conclusions
Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy.

Clinical Trials Registration
NCT01732250