"The Impact of In Vitro Synergy Between Colistin and Meropenem on Clini" by Jason M. Pogue, Michael J. Rybak et al.
 

The Impact of In Vitro Synergy Between Colistin and Meropenem on Clinical Outcomes in Invasive Carbapenem-Resistant Gram-Negative Infections: A Report From the OVERCOME Trial

Document Type

Conference Proceeding

Publication Date

11-2021

Publication Title

Open Forum Infectious Diseases

Abstract

Background

Consensus guidelines caution against colistin (COL) monotherapy due to efficacy and resistance development concerns. The COL + meropenem (MEM) combination often displays in vitro synergy against carbapenem-resistant (CR) Gram-negative bacilli (GNB). We recently completed a clinical trial comparing outcomes in patients receiving COL vs. COL + MEM. Herein we assess if, amongst patients receiving COL + MEM, outcomes differed as a function of the presence (or absence) of in vitro synergy against the index pathogen.

Methods

OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL + placebo and COL + MEM for the treatment of pneumonia and/or bloodstream infection (BSI) due to CR GNB. Baseline isolates were COL susceptible (MIC ≤ 2 mg/L) and underwent synergy testing to COL + MEM in 24-hour time kill experiments (TKE). Synergy was defined as a >2-log CFU/ml reduction with combination therapy compared to the most active single agent. Outcomes assessed included 28-day mortality, clinical failure, and the development of COL resistance (MIC ≥ 4 mg/L) for both the overall cohort and the subgroup with A. baumannii.

Results

Of the 211 patients who received COL + MEM in OVERCOME, 186 had baseline synergy testing performed and were eligible for this analysis. The median age of the cohort was 70 years, 35% were female, 48% were white, and 44% Asian. Sixty-eight percent were in the intensive care unit (ICU) at infection onset. A. baumannii was the most common pathogen (78%) and pneumonia was the most common infection (68%). Synergy was demonstrated in most isolates (76%). Baseline characteristics, clinical, and microbiological outcomes were similar amongst patients infected with isolates against which COL + MEM demonstrated synergy and those where no synergy was demonstrated (Table 1). In patients with A. baumannii infections, the presence of in vitro synergy was associated with a decrease in clinical failure (53% vs. 79%; p = 0.04). No significant impact of synergy on 28-day mortality or development of COL resistance was demonstrated (Table 2).

Conclusion

The presence of in vitro synergy via TKE was associated with a decrease in clinical failure in patients treated with COL + MEM for invasive infections due to CR A. baumannii.

Volume

8

Issue

suppl 1

First Page

S421

Comments

IDWeek 2021, Virtual, September 29 - October 3, 2021.

Last Page

S422

DOI

10.1093/ofid/ofab466.835

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