Ignacio Martin-Loeches1,2, Jean-François Timsit3, Marin H Kollef4, Richard G Wunderink5, Nobuaki Shime6, Martin Nováček7, Ülo Kivistik8, Álvaro Réa-Neto9, Christopher J Bruno10, Jennifer A Huntington10, Gina Lin10, Erin H Jensen10, Mary Motyl10, Brian Yu10, Davis Gates10, Joan R Butterton10, Elizabeth G Rhee10. 1. St James's Hospital, Trinity College Dublin, James Street, Dublin 8, Ireland. 2. Universitat de Barcelona, IDIBAPS, CIBERes, Barcelona, Spain. 3. UMR 1137, IAME, Université Paris Diderot, F75018, Paris, France. 4. Washington University School of Medicine, 4523 Clayton Ave, Campus Box 8052, St. Louis, MO 63110, USA. 5. Northwestern University Feinberg School of Medicine, 303 East Superior St, Simpson Querrey 5th Floor, Suite 5-301, Chicago, IL 60611, USA. 6. Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 7. General Hospital of Kolin, Zizkova 146, Kolin 3, 280 00, Czech Republic. 8. North Estonia Medical Centre Foundation, Sütiste tee 19, Tallinn, Harjumaa 13419, Estonia. 9. Universidade Federal do Paraná, Rua XV de Novembro, 1299 - Centro, Curitiba - PR, 80060-000, Brazil. 10. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
Abstract
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.
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.
Authors: Andre C Kalil; Mark L Metersky; Michael Klompas; John Muscedere; Daniel A Sweeney; Lucy B Palmer; Lena M Napolitano; Naomi P O'Grady; John G Bartlett; Jordi Carratalà; Ali A El Solh; Santiago Ewig; Paul D Fey; Thomas M File; Marcos I Restrepo; Jason A Roberts; Grant W Waterer; Peggy Cruse; Shandra L Knight; Jan L Brozek Journal: Clin Infect Dis Date: 2016-07-14 Impact factor: 9.079
Authors: Wilhelmina G Melsen; Maroeska M Rovers; Rolf H H Groenwold; Dennis C J J Bergmans; Christophe Camus; Torsten T Bauer; Ernst W Hanisch; Bengt Klarin; Mirelle Koeman; Wolfgang A Krueger; Jean-Claude Lacherade; Leonardo Lorente; Ziad A Memish; Lee E Morrow; Giuseppe Nardi; Christianne A van Nieuwenhoven; Grant E O'Keefe; George Nakos; Frank A Scannapieco; Philippe Seguin; Thomas Staudinger; Arzu Topeli; Miquel Ferrer; Marc J M Bonten Journal: Lancet Infect Dis Date: 2013-04-25 Impact factor: 25.071
Authors: Mariana Castanheira; Leonard R Duncan; Rodrigo E Mendes; Helio S Sader; Dee Shortridge Journal: Antimicrob Agents Chemother Date: 2018-02-23 Impact factor: 5.191
Authors: Cecilia G Carvalhaes; Mariana Castanheira; Helio S Sader; Robert K Flamm; Dee Shortridge Journal: Diagn Microbiol Infect Dis Date: 2018-11-30 Impact factor: 2.803
Authors: George H Talbot; Anita Das; Stephanie Cush; Aaron Dane; Michele Wible; Roger Echols; Antoni Torres; Sue Cammarata; John H Rex; John H Powers; Thomas Fleming; Jeffrey Loutit; Steve Hoffmann Journal: J Infect Dis Date: 2019-04-19 Impact factor: 5.226
Authors: Patrick N A Harris; Paul A Tambyah; David C Lye; Yin Mo; Tau H Lee; Mesut Yilmaz; Thamer H Alenazi; Yaseen Arabi; Marco Falcone; Matteo Bassetti; Elda Righi; Benjamin A Rogers; Souha Kanj; Hasan Bhally; Jon Iredell; Marc Mendelson; Tom H Boyles; David Looke; Spiros Miyakis; Genevieve Walls; Mohammed Al Khamis; Ahmed Zikri; Amy Crowe; Paul Ingram; Nick Daneman; Paul Griffin; Eugene Athan; Penelope Lorenc; Peter Baker; Leah Roberts; Scott A Beatson; Anton Y Peleg; Tiffany Harris-Brown; David L Paterson Journal: JAMA Date: 2018-09-11 Impact factor: 56.272