Colistin Resistance Development Following Colistin-Meropenem Combination Therapy Versus Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms.
Enterobacteriaceae
Gram-negative
carbapenem
colistin
resistance
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
17 12 2020
17 12 2020
Historique:
received:
14
08
2019
accepted:
21
11
2019
pubmed:
24
11
2019
medline:
28
4
2021
entrez:
24
11
2019
Statut:
ppublish
Résumé
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. 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). 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31758195
pii: 5638072
doi: 10.1093/cid/ciz1146
doi:
Substances chimiques
Anti-Bacterial Agents
0
Carbapenems
0
Meropenem
FV9J3JU8B1
Colistin
Z67X93HJG1
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2599-2607Investigateurs
Mical Paul
(M)
Yael Dishon Benattar
(Y)
Yaakov Dickstein
(Y)
Roni Bitterman
(R)
Hiba Zayyad
(H)
Fidi Koppel
(F)
Yael Zak-Doron
(Y)
Sergey Altunin
(S)
Nizar Andria
(N)
Ami Neuberger
(A)
Anat Stern
(A)
Neta Petersiel
(N)
Marina Raines
(M)
Amir Karban
(A)
Leonard Leibovici
(L)
Dafna Yahav
(D)
Noa Eliakim-Raz
(N)
Oren Zusman
(O)
Michal Elbaz
(M)
Heyam Atamna
(H)
Vered Daitch
(V)
Tanya Babich
(T)
Yehuda Carmeli
(Y)
Amir Nutman
(A)
Amos Adler
(A)
Inbar Levi
(I)
George L Daikos
(GL)
Anna Skiada
(A)
Ioannis Deliolanis
(I)
Ioannis Pavleas
(I)
Anastasia Antoniadou
(A)
Antigoni Kotsaki
(A)
Emanuele Durante-Mangoni
(E)
Roberto Andini
(R)
Domenico Iossa
(D)
Mariano Bernardo
(M)
Giusi Cavezza
(G)
Lorenzo Bertolino
(L)
Giuseppe Giuffre
(G)
Roberto Giurazza
(R)
Susanna Cuccurullo
(S)
Maria Galdo
(M)
Patrizia Murino
(P)
Adriano Cristinziano
(A)
Antonio Corcione
(A)
Rosa Zampino
(R)
Pia Clara Pafundi
(P)
Johan Mouton
(J)
Lena Friberg
(L)
Anders Kristoffersson
(A)
Ursula Theuretzbacher
(U)
Informations de copyright
© 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.