Colistin Resistance Development Following Colistin-Meropenem Combination Therapy Versus Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms. (23rd November 2019)

• Record Type: Journal Article
• Authors: Dickstein, Yaakov; Lellouche, Jonathan; Schwartz, David; Nutman, Amir; Rakovitsky, Nadya; Dishon Benattar, Yael; Altunin, Sergey; Bernardo, Mariano; Iossa, Domenico; Durante-Mangoni, Emanuele; Antoniadou, Anastasia; Skiada, Anna; Deliolanis, Ioannis; Daikos, George L; Daitch, Vered; Yahav, Dafna; Leibovici, Leonard; Rognås, Viktor; Friberg, Lena E; Mouton, Johan W; Paul, Mical; Carmeli, Yehuda
• Is Part Of: Clinical infectious diseases. Volume 71:Number 10(2020)
• Page Start: 2599
• Page End: 2607
• Publication Date: 2019-11-23
• Subjects: carbapenem -- colistin -- Enterobacteriaceae -- Gram-negative -- resistance; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciz1146
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: We evaluated whether carbapenem-colistin combination therapy reduces the emergence of colistin resistance, compared to colistin monotherapy, when given to patients with infections due to carbapenem-resistant Gram-negative organisms. 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 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%) versus patients randomized to colistin-meropenem combination therapy (12/108, 11.1%; P = .669). ColR-E organisms were detected in 18/249 (7.2%) patients available for analysis. No difference was observed between the 2 treatment arms (colistin monotherapy 6/128 [4.7%] vs combination therapy 12/121 [9.9%]; P = .111). Enterobacteriaceae, as the index isolate, was found to be associated with development of ColR-E (hazard ratio, 3.875; 95% confidence interval, 1.475–10.184; P = .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. Abstract : In a randomized, controlled trial, we evaluated whether colistin-meropenem combination therapy, compared to colistin monotherapy, for infections due to carbapenem-resistant Gram-negative bacteria reduces the emergence of colistin resistance. No evidence to support a reduction with combination therapy was found.