@article{2b92078132b84147b5d7fd5c2a1f20fb,
title = "Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae",
abstract = "Background The efficacy of ceftazidime-Avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown. Methods Patients initially treated with either ceftazidime-Avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-To-Treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results Thirty-eight patients were treated first with ceftazidime-Avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-Avibactam versus colistin, IPTW-Adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P =.001). In an analysis of disposition at 30 days, patients treated with ceftazidime-Avibactam, compared with those treated within colistin, had an IPTW-Adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-Avibactam to colistin. Conclusions Ceftazidime-Avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.",
author = "{Van Duin}, David and Lok, {Judith J.} and Michelle Earley and Eric Cober and Richter, {Sandra S.} and Federico Perez and Salata, {Robert A.} and Kalayjian, {Robert C.} and Watkins, {Richard R.} and Yohei Doi and Kaye, {Keith S.} and Fowler, {Vance G.} and Paterson, {David L.} and Bonomo, {Robert A.} and Scott Evans",
note = "Funding Information: Financial support. This work was supported by the National Institute of Allergy And Infectious Diseases, National Institutes of Health (NIH; awards UM1AI104681 and R21AI114508 [D. v. D. and R. A. B.], and R01AI100560, R01AI063517, and R01AI072219 [R. A. B.]; and Division of Microbiology and Infectious Diseases protocol 10–0065 and award R01AI119446-01 to K. S. K.); the Clinical and Translational Science Collaborative of Cleveland (D. v. D. and F. P.); the National Center for Advancing Translational Sciences component of the NIH and the NIH Roadmap for Medical Research (grant UL1TR000439); the NIH (Mid-Career Mentoring Award K24-AI093969 to V. G. F. and research awards R01AI104895 and R21AI107302 to Y. D.); the Cleveland Department of Veterans Affairs (award 1I01BX001974 to R. A. B. from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development and the Geriatric Research Education and Clinical Center VISN 10); the Research Program Committees of the Cleveland Clinic (D. v. D.); and the STERIS Corporation (unrestricted research grant to D. v. D.). Funding Information: Potential conflicts of interest. D. v. D. has served on advisory boards for Allergan, Achaogen, Shionogi, Tetraphase, Sanofi-Pasteur, MedImmune, and Astellas and received research funding from Steris and Scynexis. S. S. R has received research support from bioMerieux, BD Diagnostics, BioFire, OpGen, Forest Laboratories, Achaogen, Nanosphere, and Pocared, and an honorarium from bioMerieux. R. R. W. has received grant support from Allergan. Y. D. has received grant support from The Medicines Company and the NIH and has served on advisory boards for Meiji, Tetraphase, and Achaogen. K. S. K. has served as a consultant and grant investigator and on the speakers{\textquoteright} bureau for Allergan, from which he has also received a consulting fee, a grant, and a speaker honorarium; has received a grant from and served as a consultant for Merck; and has served as a consultant for Xellia and Achaogen. R. A. B. has served as a grant investigator and received grants from AstraZeneca, Merck, Melinta, Steris, the NIH, and VA Merit Review Award Program. V. G. F. has received grant or research support from Advanced Liquid Logic, Cubist, Cerexa, MedImmune, Merck, NIH, Novartis, Pfizer, and Theravance; has served as a paid consultant for Affinium, Baxter, Cerexa, Cubist, Debiopharm, Durata, Merck, Novartis, NovaDigm, The Medicines Company, MedImmune, Pfizer, Theravance, and Trius; has received honoraria from Arpida, Astellas, Cubist, Inhibitex, Merck, Pfizer, Targanta, Theravance, Wyeth, Ortho-McNeil, Novartis, and Vertex Pharmaceuticals; and has served as a Merck V710 Vaccine cochair. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed Publisher Copyright: {\textcopyright} The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",
year = "2018",
month = jan,
day = "15",
doi = "10.1093/cid/cix783",
language = "English",
volume = "66",
pages = "163--171",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "2",
}