TY - JOUR
TI - Colistin resistance development following colistin-meropenem combination therapy versus colistin monotherapy in patients with infections caused by carbapenem-resistant organisms
AU - Dickstein, Y.
AU - Lellouche, J.
AU - Schwartz, D.
AU - Nutman, A.
AU - Rakovitsky, N.
AU - Benattar, Y.D.
AU - Altunin, S.
AU - Bernardo, M.
AU - Iossa, D.
AU - Durante-Mangoni, E.
AU - Antoniadou, A.
AU - Skiada, A.
AU - Deliolanis, I.
AU - Daikos, G.L.
AU - Daitch, V.
AU - Yahav, D.
AU - Leibovici, L.
AU - Rognås, V.
AU - Friberg, L.E.
AU - Mouton, J.W.
AU - Paul, M.
AU - Carmeli, Y.
AU - Benattar, Y.D.
AU - Dickstein, Y.
AU - Bitterman, R.
AU - Zayyad, H.
AU - Koppel, F.
AU - Zak-Doron, Y.
AU - Altunin, S.
AU - Andria, N.
AU - Neuberger, A.
AU - Stern, A.
AU - Petersiel, N.
AU - Raines, M.
AU - Karban, A.
AU - Yahav, D.
AU - Eliakim-Raz, N.
AU - Zusman, O.
AU - Elbaz, M.
AU - Atamna, H.
AU - Daitch, V.
AU - Babich, T.
AU - Carmeli, Y.
AU - Nutman, A.
AU - Adler, A.
AU - Levi, I.
AU - Daikos, G.L.
AU - Skiada, A.
AU - Deliolanis, I.
AU - Pavleas, I.
AU - Antoniadou, A.
AU - Kotsaki, A.
AU - Andini, R.
AU - Iossa, D.
AU - Bernardo, M.
AU - Cavezza, G.
AU - Bertolino, L.
AU - Giuffre, G.
AU - Giurazza, R.
AU - Cuccurullo, S.
AU - Galdo, M.
AU - Murino, P.
AU - Cristinziano, A.
AU - Corcione, A.
AU - Zampino, R.
AU - Pafundi, P.C.
AU - Mouton, J.
AU - Friberg, L.
AU - Kristoffersson, A.
AU - Theuretzbacher, U.
AU - the AIDA Study Group
JO - Clinical Infectious Diseases
PY - 2020
VL - 71
TODO - 10
SP - 2599-2607
PB - Oxford University Press
SN - 1058-4838, 1537-6591
TODO - 10.1093/cid/ciz1146
TODO - 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
TODO - 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.
ER -