Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes.
Aged
Aged, 80 and over
Carbapenems
/ pharmacology
Colistin
/ administration & dosage
Cross Infection
Drug Resistance, Bacterial
Drug Synergism
Female
Gram-Negative Bacteria
/ drug effects
Gram-Negative Bacterial Infections
/ drug therapy
Humans
Male
Meropenem
/ administration & dosage
Microbial Sensitivity Tests
Middle Aged
Pneumonia, Bacterial
/ drug therapy
Treatment Outcome
Carbapenem resistance
Checkerboard assay
Colistin
Combination treatment
Gram-negative infections synergism
Journal
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
31
01
2020
revised:
21
03
2020
accepted:
27
03
2020
pubmed:
7
4
2020
medline:
3
7
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem. This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin-meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure. The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31-1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22-2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26-1.04) or 14-day mortality (aOR1.09, 95% CI 0.60-1.96). In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.
Identifiants
pubmed: 32251844
pii: S1198-743X(20)30181-6
doi: 10.1016/j.cmi.2020.03.035
pii:
doi:
Substances chimiques
Carbapenems
0
Meropenem
FV9J3JU8B1
Colistin
Z67X93HJG1
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1185-1191Investigateurs
Mical Paul
(M)
Yael Dishon Benattar
(YD)
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 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
(PC)
Johan Mouton
(J)
Lena Friberg
(L)
Anders Kristoffersson
(A)
Ursula Theuretzbacher
(U)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.