The Association between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria: A Prospective Study.

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The Association between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria: A Prospective Study.

Clin Infect Dis. 2018 Apr 27;:

Authors: Zak-Doron Y, Dishon Benattar Y, Pfeffer I, Daikos GL, Skiada A, Antoniadou A, Durante-Mangoni E, Andini R, Cavezza G, Leibovici L, Yahav D, Elyakim-Raz N, Carmeli Y, Nutman A, Paul M, AIDA study group

Abstract
Background: Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB).
Methods: Secondary analysis of a randomized-controlled trial, including adults with bloodstream infections (BSI), pneumonia or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day all-cause mortality. We adjusted the analyses by multivariable regression analysis and propensity score (PS)-matching.
Results: The study included 406 inpatients with severe CRGNB infections, mostly A. baumannii (312/406, 77%). Covering EAT was given to 209 (51.5%) patients, consisting of colistin as the in-vitro covering antibiotic in 200 (95.7%). Patients receiving non-covering EAT were older, more frequently unconscious and dependent, carrying more catheters and mechanically-ventilated with pneumonia. Mortality was 84/197 (42.6%) with non-covering, compared to 96/209 (45.9%) with covering EAT (p=0.504). Covering EAT was not associated with survival in the adjusted analysis, rather there was a weak association with mortality (OR 1.37, 95% CI 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the PS-matched cohort (N=338), there were no significant differences between the groups and covering antibiotics were not significantly associated with mortality, OR 1.42 (95% CI 0.91-2.22). Similar results were obtained in an analysis of 14-day mortality.
Conclusions: Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

PMID: 29718143 [PubMed - as supplied by publisher]

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