Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms
Keith S. Kaye, Dror Marchaim, Visanu Thamlikitkul, Yehuda Carmeli, Cheng‐Hsun Chiu, George L. Daikos, Sorabh Dhar, Emanuele Durante‐Mangoni, Achilleas Gikas, Αναστασία Κοτανίδου, Mical Paul, Emmanuelle Roilides, Michael J. Rybak, Michael Samarkos, Matthew Sims, Dora Tancheva, Sotirios Tsiodras, Daniel H. Kett, Gopi Patel, David P. Calfee, Leonard Leibovici, Laura E. Power, L. Silvia Muñoz-Price, Kurt Stevenson, Laura Susick, Katie Latack, Jolene Daniel, Christine C. Chiou, George Divine, Varduhi Ghazyaran, Jason M. Pogue
Abstract
BACKGROUND: , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: , or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).