TY - JOUR
T1 - Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia
AU - Martin-Loeches, Ignacio
AU - Timsit, Jean François
AU - Kollef, Marin H.
AU - Wunderink, Richard G.
AU - Shime, Nobuaki
AU - Nováček, Martin
AU - Kivistik, Ülo
AU - Réa-Neto, Álvaro
AU - Bruno, Christopher J.
AU - Huntington, Jennifer A.
AU - Lin, Gina
AU - Jensen, Erin H.
AU - Motyl, Mary
AU - Yu, Brian
AU - Gates, Davis
AU - Butterton, Joan R.
AU - Rhee, Elizabeth G.
N1 - Funding Information:
Employees of the funder, including several of the co-authors, were involved in the design, execution, analysis or reporting of the research. All authors had full access to the study data and take joint responsibility for this article. I.M.-L. has received institutional research funding from MSD and has also received personal fees from MSD, Pfizer, bioMérieux and Gilead, and grants from Grifols. J.-F.T. has received institutional research funding from MSD and has also received grants from MSD, bioMérieux and Brahms, and personal fees from MSD, Pfizer, Gilead, Becton, Dickinson and Company, Shionogi and Nabriva. M.H.K. has received institutional research funding from MSD and has also received advisory board and speaker’s bureau fees from MSD. R.G.W. has received institutional research funding from MSD and has also received grants and personal fees from MSD, Shionogi, Polyphor, Melinta, The Medicines Company and Arsanis, and personal fees from Microbiotix, KBP Biosciences and Meiji Seika. N.S. has received institutional research funding from MSD and has also received lecture fees from MSD. M.N., Ü.K. and Á.R.-N have received investigator fees and institutional research funding from MSD. C.J.B., J.A.H., G.L., E.H.J., M.M., B.Y., D.G., J.R.B. and E.G.R. are employees of MSD and may hold stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. None of the authors received any reimbursement for preparing this article.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). Medical writing assistance was provided by Dominik Wolf, MSc, of MSD, and Susan E. DeRocco, PhD, of The Lockwood Group, Stamford, CT, USA. This assistance was funded by MSD.
Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Objectives: In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. Methods: Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population. Results: The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable. Conclusions: In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.
AB - Objectives: In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated. Methods: Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population. Results: The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable. Conclusions: In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.
UR - http://www.scopus.com/inward/record.url?scp=85128160020&partnerID=8YFLogxK
U2 - 10.1093/jac/dkab494
DO - 10.1093/jac/dkab494
M3 - Article
C2 - 35022730
AN - SCOPUS:85128160020
VL - 77
SP - 1166
EP - 1177
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 4
ER -