| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
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 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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