TY - JOUR
T1 - Colistin resistance development following colistin-meropenem combination therapy versus colistin monotherapy in patients with infections caused by carbapenem-resistant organisms
AU - the AIDA Study Group
AU - Dickstein, Yaakov
AU - Lellouche, Jonathan
AU - Schwartz, David
AU - Nutman, Amir
AU - Rakovitsky, Nadya
AU - Benattar, Yael Dishon
AU - Altunin, Sergey
AU - Bernardo, Mariano
AU - Iossa, Domenico
AU - Durante-Mangoni, Emanuele
AU - Antoniadou, Anastasia
AU - Skiada, Anna
AU - Deliolanis, Ioannis
AU - Daikos, George L.
AU - Daitch, Vered
AU - Yahav, Dafna
AU - Leibovici, Leonard
AU - Rognås, Viktor
AU - Friberg, Lena E.
AU - Mouton, Johan W.
AU - Paul, Mical
AU - Carmeli, Yehuda
AU - Paul, Mical
AU - Benattar, Yael Dishon
AU - Dickstein, Yaakov
AU - Bitterman, Roni
AU - Zayyad, Hiba
AU - Koppel, Fidi
AU - Zak-Doron, Yael
AU - Altunin, Sergey
AU - Andria, Nizar
AU - Neuberger, Ami
AU - Stern, Anat
AU - Petersiel, Neta
AU - Raines, Marina
AU - Karban, Amir
AU - Leibovici, Leonard
AU - Yahav, Dafna
AU - Eliakim-Raz, Noa
AU - Zusman, Oren
AU - Elbaz, Michal
AU - Atamna, Heyam
AU - Daitch, Vered
AU - Babich, Tanya
AU - Adler, Amos
AU - Levi, Inbar
AU - Daikos, George L.
AU - Skiada, Anna
N1 - Publisher Copyright:
© The Author(s) 2019.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/11/15
Y1 - 2020/11/15
N2 - 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.
AB - 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.
KW - Carbapenem
KW - Colistin
KW - Enterobacteriaceae
KW - Gram-negative
KW - Resistance
UR - http://www.scopus.com/inward/record.url?scp=85086927427&partnerID=8YFLogxK
U2 - 10.1093/cid/ciz1146
DO - 10.1093/cid/ciz1146
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C2 - 31758195
AN - SCOPUS:85086927427
SN - 1058-4838
VL - 71
SP - 2599
EP - 2607
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -