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

מאת: 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
פורסם ב: Clinical Microbiology and Infection
תיאור: 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
SDGs : SDG 03  |  יחידות:   | מועד: 2020 |  קישור