Yaakov Dickstein1, Jonathan Lellouche1,2, Maayan Ben Dalak Amar1,2, David Schwartz1,2, Amir Nutman1,3, Vered Daitch3,4, Dafna Yahav3,5, Leonard Leibovici3,4, Anna Skiada6,7, Anastasia Antoniadou7,8, George L Daikos6,7, Roberto Andini9, Rosa Zampino9, Emanuele Durante-Mangoni9, Johan W Mouton10, Lena E Friberg11, Yael Dishon Benattar12,13, Roni Bitterman12, Ami Neuberger12, Yehuda Carmeli1,2,3, Mical Paul12,14. 1. National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel-Aviv. 2. Molecular Epidemiology Laboratory, Tel-Aviv Sourasky Medical Center. 3. Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv. 4. Department of Medicine E, Beilinson Hospital, Petah Tikva, Israel. 5. Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 6. First Department of Medicine, Laikon General Hospital, Athens, Greece. 7. National and Kapodistrian University of Athens, Athens, Greece. 8. Fourth Department of Medicine, Attikon University General Hospital, Athens, Greece. 9. Department of Precision Medicine, University of Campania 'L Vanvitelli' and Azienda Ospedaliera di Rilievo Nazionale dei Colli-Monaldi Hospital, Napoli, Italy. 10. Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands. 11. Department of Pharmaceutical Biosciences, Uppsala University, Sweden. 12. Institute of Infectious Diseases, Rambam Health Care Campus. 13. Cheryl Spencer Department of Nursing, University of Haifa. 14. Faculty of Medicine, Technion, Israel Institute of Technology, Haifa.
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.
RCT Entities:
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.
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