Details

Autor(en) / Beteiligte

• Nutman, Amir
• Lellouche, Jonathan
• Temkin, Elizabeth
• Daikos, George
• Skiada, Anna
• Durante-Mangoni, Emanuele
• Dishon-Benattar, Yael
• Bitterman, Roni
• Yahav, Dafna
• Daitch, Vered
• Bernardo, Mariano
• Iossa, Domenico
• Zusman, Oren
• Friberg, Lena E.
• Mouton, Johan W.
• Theuretzbacher, Ursula
• Leibovici, Leonard
• Paul, Mical
• Carmeli, Yehuda
• Benattar, Yael Dishon
• Dickstein, Yaakov
• Zayyad, Hiba
• Koppel, Fidi
• Zak-Doron, Yael
• Altunin, Sergey
• Andria, Nizar
• Neuberger, Ami
• Stern, Anat
• Petersiel, Neta
• Raines, Marina
• Karban, Amir
• Eliakim-Raz, Noa
• Elbaz, Michal
• Atamna, Heyam
• Babich, Tanya
• Adler, Amos
• Levi, Inbar
• Daikos, George L.
• Pavleas, Ioannis
• Antoniadou, Anastasia
• Kotsaki, Antigoni
• Andini, Roberto
• Cavezza, Giusi
• Bertolino, Lorenzo
• Giuffre, Giuseppe
• Giurazza, Roberto
• Cuccurullo, Susanna
• Galdo, Maria
• Murino, Patrizia
• Cristinziano, Adriano
• Corcione, Antonio
• Zampino, Rosa
• Pafundi, Pia Clara
• Mouton, Johan
• Friberg, Lena
• Kristoffersson, Anders

Titel

Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes

Ist Teil von

• Clinical microbiology and infection, 2020-09, Vol.26 (9), p.1185-1191

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.