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[Online ahead of print]

Colistin Resistance Development Following Colistin-Meropenem Combination Therapy vs. Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms

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Colistin Resistance Development Following Colistin-Meropenem Combination Therapy vs. Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms

Yaakov Dickstein et al. Clin Infect Dis.

Abstract

Background: We evaluated whether carbapenem-colistin combination therapy given to patients with infections due to carbapenem-resistant Gram-negative organisms reduces the emergence of colistin resistance compared to colistin monotherapy.

Methods: This is a pre-planned analysis of a secondary outcome from a randomized controlled trial comparing colistin monotherapy with colistin-meropenem combination for the treatment of severe infections caused by carbapenem-resistant, colistin-susceptible Gram-negative bacteria. We evaluated rectal swabs taken on day 7 from enrollment or later for the presence of new colistin-resistant (ColR) isolates. We evaluated the emergence of any ColR isolate and the emergence of ColR Enterobacteriaceae (ColR-E).

Results: Data were available for 214 patients for the primary analysis; emergent ColR organisms were detected in 22 (10.3%). No difference was observed between patients randomized to treatment with colistin monotherapy (10/106, 9.4%) vs. patients randomized to colistin-meropenem combination therapy (12/108, 11.1%), p=0.669. ColR-E organisms were detected in 18/249 (7.2%) patients available for analysis. No difference was observed between the two treatment arms (colistin monotherapy 6/128 [4.7%] vs. combination therapy 12/121 [9.9%], p=0.111). Enterobacteriaceae as the index isolate was found to be associated with development of ColR-E (HR 3.875 95% CI 1.475-10.184, p=0.006).

Conclusions: Carbapenem-colistin combination therapy did not reduce the incidence of colistin resistance emergence in patients with infections due to carbapenem-resistant organisms. Further studies are necessary to elucidate the development of colistin resistance and methods for its prevention.

Keywords: Carbapenem; Colistin; Enterobacteriaceae; Gram-negative; Resistance.

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