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Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia

A Multicenter Prospective Observational Study*

Cheng, Aristine M.B.B.Chir1,2; Chuang, Yu-Chung MD3; Sun, Hsin-Yun MD1; Sheng, Wang-Huei MD, PhD1; Yang, Chia-Jui MD4; Liao, Chun-Hsing MD4; Hsueh, Po-Ren MD1,6; Yang, Jia-Ling MD5; Shen, Ni-Jiin MD5; Wang, Jann-Tay MD, PhD1; Hung, Chien-Ching MD, PhD1; Chen, Yee-Chun MD, PhD1; Chang, Shan-Chwen MD, PhD1

doi: 10.1097/CCM.0000000000000933
Clinical Investigations

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 to 2013 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.

1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

2Department of Internal Medicine, National Taiwan University Hospital Hsin-chu Branch, Hsin-chu, Taiwan.

3Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

4Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

5Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-lin, Taiwan.

6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.

* See also p. 1332.

Drs. Cheng and Chuang are co-first authors.

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Dr. Cheng received support for travel (Interscience Conference of Antimicrobial Agents and Chemotherapy 2011 Travel Grant and European Congress of Clinical Microbiology and Infectious Diseases 2012 Travel Grant). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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