Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes
| Autor: | Amir Nutman, Jonathan Lellouche, Elizabeth Temkin, George Daikos, Anna Skiada, Emanuele Durante-Mangoni, Yael Dishon-Benattar, Roni Bitterman, Dafna Yahav, Vered Daitch, Mariano Bernardo, Domenico Iossa, Oren Zusman, Lena E. Friberg, Johan W. Mouton, Ursula Theuretzbacher, Leonard Leibovici, Mical Paul, Yehuda Carmeli, Yael Dishon Benattar, Yaakov Dickstein, Hiba Zayyad, Fidi Koppel, Yael Zak-Doron, Sergey Altunin, Nizar Andria, Ami Neuberger, Anat Stern, Neta Petersiel, Marina Raines, Amir Karban, Noa Eliakim-Raz, Michal Elbaz, Heyam Atamna, Tanya Babich, Amos Adler, Inbar Levi, George L. Daikos, Ioannis Pavleas, Anastasia Antoniadou, Antigoni Kotsaki, Roberto Andini, Giusi Cavezza, Lorenzo Bertolino, Giuseppe Giuffre, Roberto Giurazza, Susanna Cuccurullo, Maria Galdo, Patrizia Murino, Adriano Cristinziano, Antonio Corcione, Rosa Zampino, Pia Clara Pafundi, Johan Mouton, Lena Friberg, Anders Kristoffersson |
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| Přispěvatelé: | Medical Microbiology & Infectious Diseases, 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. |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Polymyxin Infektionsmedicin law.invention Checkerboard assay 0302 clinical medicine Randomized controlled trial law polycyclic compounds 030212 general & internal medicine Gram Aged 80 and over Cross Infection biology Drug Synergism General Medicine Middle Aged Acinetobacter baumannii Gram-negative infections synergism Infectious Diseases Treatment Outcome Female medicine.drug Microbiology (medical) Infectious Medicine medicine.medical_specialty Carbapenem resistance medicine.drug_class 030106 microbiology Microbial Sensitivity Tests Meropenem 03 medical and health sciences Internal medicine Drug Resistance Bacterial Gram-Negative Bacteria medicine Pneumonia Bacterial Humans Aged business.industry Colistin Odds ratio biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Carbapenems Combination treatment bacteria business Antagonism Gram-Negative Bacterial Infections |
| Zdroj: | Clinical Microbiology and Infection, 26(9), 1185-1191. Elsevier Ltd. |
| ISSN: | 1469-0691 1198-743X |
| 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. |
| Databáze: | OpenAIRE |
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