{"doi":"10.1093/jac/dkab494","title":"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","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.","journal":"Journal of Antimicrobial Chemotherapy","year":2021,"id":175982,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":496395,"name":"Jean‐François Timsit","orcid":null,"position":1,"is_corresponding":false},{"id":420204,"name":"Marin H. Kollef","orcid":"0000-0003-0671-0751","position":2,"is_corresponding":false},{"id":266702,"name":"Richard G. Wunderink","orcid":"0000-0002-8527-4195","position":3,"is_corresponding":false},{"id":588791,"name":"Nobuaki Shime","orcid":"0000-0002-9113-6151","position":4,"is_corresponding":false},{"id":717866,"name":"Martin Nováček","orcid":"0009-0002-5738-4394","position":5,"is_corresponding":false},{"id":718525,"name":"Ülo Kivistik","orcid":null,"position":6,"is_corresponding":false},{"id":717867,"name":"Álvaro Réa-Neto","orcid":"0000-0001-5524-0907","position":7,"is_corresponding":false},{"id":717868,"name":"Christopher Bruno","orcid":"0000-0003-2056-7170","position":8,"is_corresponding":false},{"id":718526,"name":"Jennifer A. Huntington","orcid":null,"position":9,"is_corresponding":false},{"id":718527,"name":"Gina Lin","orcid":null,"position":10,"is_corresponding":false},{"id":631208,"name":"Erin Jensen","orcid":null,"position":11,"is_corresponding":false},{"id":717869,"name":"Mary Motyl","orcid":"0000-0003-3142-8475","position":12,"is_corresponding":false},{"id":717870,"name":"Brian Yu","orcid":"0000-0001-5250-1892","position":13,"is_corresponding":false},{"id":718528,"name":"Davis Gates","orcid":null,"position":14,"is_corresponding":false},{"id":718529,"name":"Joan R. Butterton","orcid":null,"position":15,"is_corresponding":false},{"id":717871,"name":"Elizabeth G. Rhee","orcid":"0000-0001-7982-1714","position":16,"is_corresponding":false},{"id":717865,"name":"Ignacio Martín‐Loeches","orcid":"0000-0002-5834-4063","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"35022730","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}