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.

Autor:	Martin-Loeches I; St James's Hospital, Trinity College Dublin, James Street, Dublin 8, Ireland.; Universitat de Barcelona, IDIBAPS, CIBERes, Barcelona, Spain., Timsit JF; UMR 1137, IAME, Université Paris Diderot, F75018, Paris, France., Kollef MH; Washington University School of Medicine, 4523 Clayton Ave, Campus Box 8052, St. Louis, MO 63110, USA., Wunderink RG; Northwestern University Feinberg School of Medicine, 303 East Superior St, Simpson Querrey 5th Floor, Suite 5-301, Chicago, IL 60611, USA., Shime N; Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan., Nováček M; General Hospital of Kolin, Zizkova 146, Kolin 3, 280 00, Czech Republic., Kivistik Ü; North Estonia Medical Centre Foundation, Sütiste tee 19, Tallinn, Harjumaa 13419, Estonia., Réa-Neto Á; Universidade Federal do Paraná, Rua XV de Novembro, 1299 - Centro, Curitiba - PR, 80060-000, Brazil., Bruno CJ; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Huntington JA; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Lin G; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Jensen EH; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Motyl M; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Yu B; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Gates D; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Butterton JR; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA., Rhee EG; Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2022 Mar 31; Vol. 77 (4), pp. 1166-1177.
DOI:	10.1093/jac/dkab494
Abstrakt:	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. (© 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.)
Databáze:	MEDLINE
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