Excess Mortality Associated with Colistin-Tigecycline Compared with Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study
Journal
Critical Care Medicine
Journal Volume
43
Journal Issue
6
Pages
1194-1204
Date Issued
2015
Author(s)
Yang C.-J.
Liao C.-H.
Yang J.-L.
Shen N.-J.
Abstract
Objectives: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Design: Prospective, observational, multicenter study. Setting, Patients, and Interventions: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to2 013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Measurements and Main Results: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p = 0.105) and 69% versus 50% (p = 0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p = 0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p = 0.009). Conclusions: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia. ? 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
SDGs
Other Subjects
carbapenem; colistin; tigecycline; antiinfective agent; carbapenem derivative; colistin; minocycline; tigecycline; Acinetobacter infection; adult; aged; antibiotic therapy; Article; comorbidity; concentration at steady-state; disease association; disease severity; human; major clinical study; minimum inhibitory concentration; mortality; multicenter study; nonhuman; observational study; primary infection; priority journal; prospective study; Sequential Organ Failure Assessment Score; Taiwan; Acinetobacter Infections; analogs and derivatives; clinical trial; drug combination; female; intensive care unit; Kaplan Meier method; male; microbial sensitivity test; middle aged; mortality; multidrug resistance; organ dysfunction score; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Organ Dysfunction Scores; Prospective Studies; Taiwan
Type
journal article