@article{cb1fe88277a4492bbdd65d372bf17747,
title = "In vitro discordance with in vivo activity: Humanized exposures of ceftazidime-avibactam, aztreonam, and tigecycline alone and in combination against New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae in a murine lung infection model",
abstract = "The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)-producing bacteria remains clinically challenging given the multidrug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM-positive Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10 CFU bacterial reduction; therefore, no in vivo synergy was observed.",
keywords = "Ceftazidime-avibactam, Klebsiella pneumoniae, New Delhi metallo-β-lactamase, Resistance",
author = "Monogue, {M. L.} and Abbo, {L. M.} and R. Rosa and Camargo, {J. F.} and O. Martinez and Bonomo, {R. A.} and Nicolau, {D. P.}",
note = "Funding Information: This study was supported in part by funds and facilities provided by the Cleveland Department of Veterans Affairs, Veterans Affairs Merit Review Program award no. 1I01BX001974, the Biomedical Laboratory Research & Development Service of the VA Office of Research, and the Development and the Geriatric Research Education and Clinical Center VISN 10 to R.A.B. This work was also supported by funds from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award no. R01AI063517, R01AI072219, and R01AI100560 to R.A.B. Funding Information: We thank Jennifer Tabor-Rennie, Sara Robinson, Debora Santini, Elizabeth Cyr, Christina Sutherland, Kimelyn Greenwood, Islam Ghazi, Abrar Thabit, Kamilia Abdelraouf, and Mordechai Grupper from the Center for Anti-Infective Research and Development, Hartford, CT, for their assistance with conducting this study. This study was supported in part by funds and facilities provided by the Cleveland Department of Veterans Affairs, Veterans Affairs Merit Review Program award no. 1I01BX001974, the Biomedical Laboratory Research & Development Service of the VA Office of Research, and the Development and the Geriatric Research Education and Clinical Center VISN 10 to R.A.B. This work was also supported by funds from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award no. R01AI063517, R01AI072219, and R01AI100560 to R.A.B. Funding organizations were not involved in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation, review, and approval of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. Publisher Copyright: {\textcopyright} 2017 American Society for Microbiology. All Rights Reserved.",
year = "2017",
month = jun,
doi = "10.1128/AAC.00486-17.",
language = "English (US)",
volume = "61",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "7",
}