Περίληψη:
Objectives: 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. Methods: 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. Results: 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). Discussion: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit. © 2020 European Society of Clinical Microbiology and Infectious Diseases
Συγγραφείς:
Nutman, A.
Lellouche, J.
Temkin, E.
Daikos, G.
Skiada, A.
Durante-Mangoni, E.
Dishon-Benattar, Y.
Bitterman, R.
Yahav, D.
Daitch, V.
Bernardo, M.
Iossa, D.
Zusman, O.
Friberg, L.E.
Mouton, J.W.
Theuretzbacher, U.
Leibovici, L.
Paul, M.
Carmeli, Y.
Benattar, Y.D.
Dickstein, Y.
Zayyad, H.
Koppel, F.
Zak-Doron, Y.
Altunin, S.
Andria, N.
Neuberger, A.
Stern, A.
Petersiel, N.
Raines, M.
Karban, A.
Eliakim-Raz, N.
Elbaz, M.
Atamna, H.
Babich, T.
Adler, A.
Levi, I.
Daikos, G.L.
Pavleas, I.
Antoniadou, A.
Kotsaki, A.
Andini, R.
Cavezza, G.
Bertolino, L.
Giuffre, G.
Giurazza, R.
Cuccurullo, S.
Galdo, M.
Murino, P.
Cristinziano, A.
Corcione, A.
Zampino, R.
Pafundi, P.C.
Mouton, J.
Friberg, L.
Kristoffersson, A.
AIDA Study Group
Λέξεις-κλειδιά:
colistin; meropenem; carbapenem derivative; colistin; meropenem, adult; aged; antibiotic therapy; Article; bacterium isolate; bloodstream infection; carbapenem resistance; carbapenem resistant Acinetobacter baumannii; carbapenem resistant Pseudomonas aeruginosa; carbapenem-resistant Enterobacteriaceae; clinical outcome; combination drug therapy; controlled study; drug potentiation; female; Gram negative infection; hospital acquired pneumonia; human; in vitro study; major clinical study; male; monotherapy; mortality; priority journal; secondary analysis; urinary tract infection; ventilator associated pneumonia; antibiotic resistance; bacterial pneumonia; clinical trial; cross infection; drug effect; Gram negative bacterium; Gram negative infection; microbial sensitivity test; microbiology; middle aged; multicenter study; randomized controlled trial; treatment outcome; very elderly, Aged; Aged, 80 and over; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Treatment Outcome
