@article{3120522,
    title = "Colistin resistance development following colistin-meropenem combination therapy versus colistin monotherapy in patients with infections caused by carbapenem-resistant organisms",
    author = "Dickstein, Y. and Lellouche, J. and Schwartz, D. and Nutman, A. and Rakovitsky, N. and Benattar, Y.D. and Altunin, S. and Bernardo, M. and Iossa, D. and Durante-Mangoni, E. and Antoniadou, A. and Skiada, A. and Deliolanis, I. and Daikos, G.L. and Daitch, V. and Yahav, D. and Leibovici, L. and Rognås, V. and Friberg, L.E. and Mouton, J.W. and Paul, M. and Carmeli, Y. and Benattar, Y.D. and Dickstein, Y. and Bitterman, R. and Zayyad, H. and Koppel, F. and Zak-Doron, Y. and Altunin, S. and Andria, N. and Neuberger, A. and Stern, A. and Petersiel, N. and Raines, M. and Karban, A. and Yahav, D. and Eliakim-Raz, N. and Zusman, O. and Elbaz, M. and Atamna, H. and Daitch, V. and Babich, T. and Carmeli, Y. and Nutman, A. and Adler, A. and Levi, I. and Daikos, G.L. and Skiada, A. and Deliolanis, I. and Pavleas, I. and Antoniadou, A. and Kotsaki, A. and Andini, R. and Iossa, D. and Bernardo, M. and Cavezza, G. and Bertolino, L. and Giuffre, G. and Giurazza, R. and Cuccurullo, S. and Galdo, M. and Murino, P. and Cristinziano, A. and Corcione, A. and Zampino, R. and Pafundi, P.C. and Mouton, J. and Friberg, L. and Kristoffersson, A. and Theuretzbacher, U. and the AIDA Study Group",
    journal = "Clinical Infectious Diseases",
    year = "2020",
    volume = "71",
    number = "10",
    pages = "2599-2607",
    publisher = "Oxford University Press",
    issn = "1058-4838, 1537-6591",
    doi = "10.1093/cid/ciz1146",
    keywords = "aminoglycoside;  carbapenem;  colistin;  glycopeptide;  meropenem;  metronidazole;  penicillin derivative;  quinolone derivative;  tigecycline;  antiinfective agent;  carbapenem derivative;  colistin;  meropenem, Acinetobacter baumannii;  adult;  aged;  Article;  bacteremia;  bacterium detection;  bacterium isolate;  carbapenem-resistant Enterobacteriaceae;  colistin resistance;  combination drug therapy;  comparative effectiveness;  controlled study;  Enterobacteriaceae infection;  Escherichia coli;  female;  hospital acquired pneumonia;  human;  in vivo study;  Klebsiella pneumoniae;  major clinical study;  male;  monotherapy;  nonhuman;  priority journal;  Pseudomonas aeruginosa;  randomized controlled trial;  rectal swab;  urosepsis;  ventilator associated pneumonia;  Gram negative bacterium;  microbial sensitivity test, Anti-Bacterial Agents;  Carbapenems;  Colistin;  Gram-Negative Bacteria;  Humans;  Meropenem;  Microbial Sensitivity Tests",
    abstract = "Background. We evaluated whether carbapenem-colistin combination therapy reduces the emergence of colistin resistance, compared to colistin monotherapy, when given to patients with infections due to carbapenem-resistant Gram-negative organisms. Methods. This is a pre-planned analysis of a secondary outcome from a randomized, controlled trial comparing colistin monotherapy with colistin-meropenem combination for the treatment of severe infections caused by carbapenem-resistant, colistin-susceptible Gram-negative bacteria. We evaluated rectal swabs taken on Day 7 or later for the presence of new colistin-resistant (ColR) isolates. We evaluated the emergence of any ColR isolate and the emergence of ColR Enterobacteriaceae (ColR-E). Results. Data were available for 214 patients for the primary analysis; emergent ColR organisms were detected in 22 (10.3%). No difference was observed between patients randomized to treatment with colistin monotherapy (10/106, 9.4%) versus patients randomized to colistin-meropenem combination therapy (12/108, 11.1%; P = .669). ColR-E organisms were detected in 18/249 (7.2%) patients available for analysis. No difference was observed between the 2 treatment arms (colistin monotherapy 6/128 [4.7%] vs combination therapy 12/121 [9.9%]; P = .111). Enterobacteriaceae, as the index isolate, was found to be associated with development of ColR-E (hazard ratio, 3.875; 95% confidence interval, 1.475–10.184; P = .006). Conclusions. Carbapenem-colistin combination therapy did not reduce the incidence of colistin resistance emergence in patients with infections due to carbapenem-resistant organisms. Further studies are necessary to elucidate the development of colistin resistance and methods for its prevention. © The Author(s) 2019."
}