Treatment Outcomes of Colistin- And Carbapenem-resistant Acinetobacter baumannii Infections: An Exploratory Subgroup Analysis of a Randomized Clinical Trial

Yaakov Dickstein, Jonathan Lellouche, Maayan Ben Dalak Amar, David Schwartz, Amir Nutman, Vered Daitch, Dafna Yahav, Leonard Leibovici, Anna Skiada, Anastasia Antoniadou, George L. Daikos, Roberto Andini, Rosa Zampino, Emanuele Durante-Mangoni, Johan W. Mouton, Lena E. Friberg, Yael Dishon Benattar, Roni Bitterman, Ami Neuberger, Yehuda CarmeliMical Paul, Hiba Zayyad, Fidi Koppel, Yael Zak-Doron, Sergey Altunin, Nizar Andria, Anat Stern, Neta Petersiel, Marina Raines, Amir Karban, Noa Eliakim-Raz, Oren Zusman, Michal Elbaz, Heyam Atamna, Tanya Babich, Amos Adler, Inbar Levi, Ioannis Pavleas, Antigoni Kotsaki, Domenico Iossa, Mariano Bernardo, Giusi Cavezza, Lorenzo Bertolino, Giuseppe Giuffre, Roberto Giurazza, Susanna Cuccurullo, Maria Galdo, Patrizia Murino, Adriano Cristinziano, Antonio Corcione, Pia Clara Pafundi

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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.

Original languageEnglish
Article numberciy988
Pages (from-to)769-777
Number of pages9
JournalClinical Infectious Diseases
Volume69
Issue number5
DOIs
StatePublished - 16 Aug 2019

Bibliographical note

Publisher Copyright:
© 2018 The Author(s) 2018.

Funding

Financial support. This work was funded by the European Commission FP7 AIDA Project (Preserving Old Antibiotics for the Future: Assessment of Clinical Efficacy by a Pharmacokinetic/Pharmacodynamic Approach to Optimize Effectiveness and Reduce Resistance for Off-Patent Antibiotics) (grant number Health-F3-2011–278348).

FundersFunder number
European Commission FP7 AIDAHealth-F3-2011–278348

    Keywords

    • Acinetobacter
    • XDR-TB
    • carbapenem-resistant
    • colistin
    • gram-negative bacteria

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