The empirical use of colistin with or without a carbapenem was not associated with survival following severe infections with carbapenem-resistant Gram-negative bacteria (CRGNB), according to research published in Clinical Infectious Diseases.
A secondary analysis of a randomized controlled trial including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB was performed to determine the association between covering empirical antibiotics and mortality.
A total of 406 patients with CRGNB infections was included in the study. The majority of infections (77%) were caused by Acinetobacter baumannii. Covering empirical antibiotics was administered to 51.5% of patients, of whom 95.7% received in vitro antibiotics consisting of colistin.
Mortality in patients receiving non-covering empirical antibiotics was 42.6% and 45.9% in patients receiving covering empirical antibiotics (P =.504). Adjusted analysis using multivariable regression and propensity scoring indicated that covering empirical antibiotics was not associated with survival (odds ratio [OR] 1.37; 95% CI, 1.02-1.84). The results were similar using colistin monotherapy and a colistin-carbapenem combination. In a propensity score matched cohort (N=338) investigators found no significant differences between the groups and covering antibiotics were not associated with mortality (OR 1.42; 95% CI, 0.91-2.22).
The study may be biased towards showing no effect because participants were participating in a randomized control trial comparing colistin monotherapy to colistin-meropenem combination therapy, which means that all patients survived to pathogen identification and received targeted covering therapy. Therefore, it is unknown whether empirical therapy can prevent early deaths, which may introduce bias. The study was also not powered for analysis of separate sources of infection, although the results in the subgroup with bloodstream infections were similar.
Investigators concluded that there was no association between the start of colistin before final culture results and survival and believe that “restricting empirical use of colistin and avoiding carbapenems for CRGNB infection are important strategies for antibiotic stewardship in hospitals.”
Disclosures: George L. Daikos has received research funding from Pfizer, Achaogen, Rempex, MSD and Gilead. Emanuele Durante-Mangoni has received research funding from MSD, Pfizer, Bio-Merieux, Abbvie, Sanofi-Aventis, Medtronic and DiaSorin. Yehuda Carmeli has received research funding from MSD, AstraZeneca, Allecra Therapeutics, DaVoltera, Intercell AG, BioMerieux SA, Rempex pharmaceuticals, Nariva, Achoagen, Roche, Pfizer and Shionogi.
Zak-Doron Y, Benattar Y, Pfeffer I, et al; AIDA study group. The association between empirical antibiotic treatment and mortality in severe infections caused by carbapenem-resistant gram-negative bacteria: A prospective study [published online April 27 2018]. Clin Infect Dis. doi:10.1093/cid/ciy371