• Clin. Infect. Dis. · Dec 2020

    Randomized Controlled Trial

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

    • Yaakov Dickstein, Jonathan Lellouche, David Schwartz, Amir Nutman, Nadya Rakovitsky, Dishon Benattar Yael Y Institute of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel., Sergey Altunin, Mariano Bernardo, Domenico Iossa, Emanuele Durante-Mangoni, Anastasia Antoniadou, Anna Skiada, Ioannis Deliolanis, George L Daikos, Vered Daitch, Dafna Yahav, Leonard Leibovici, Viktor Rognås, Lena E Friberg, Johan W Mouton, Mical Paul, Yehuda Carmeli, and AIDA Study Group.
    • Institute of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel.
    • Clin. Infect. Dis. 2020 Dec 17; 71 (10): 2599-2607.

    BackgroundWe 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.MethodsThis 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).ResultsData 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).ConclusionsCarbapenem-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.© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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