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Clinical Trial
. 2022 Mar 31;77(4):1166-1177.
doi: 10.1093/jac/dkab494.

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

Ignacio Martin-Loeches  1   2 , Jean-François Timsit  3 , Marin H Kollef  4 , Richard G Wunderink  5 , Nobuaki Shime  6 , Martin Nováček  7 , Ülo Kivistik  8 , Álvaro Réa-Neto  9 , Christopher J Bruno  10 , Jennifer A Huntington  10 , Gina Lin  10 , Erin H Jensen  10 , Mary Motyl  10 , Brian Yu  10 , Davis Gates  10 , Joan R Butterton  10 , Elizabeth G Rhee  10
Affiliations
Clinical Trial

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

Ignacio Martin-Loeches et al. J Antimicrob Chemother. .

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.

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References

    1. Kalil AC, Metersky ML, Klompas M et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63: e61–111. - PMC - PubMed
    1. Melsen WG, Rovers MM, Groenwold RHH et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013; 13: 665–71. - PubMed
    1. Talbot GH, Das A, Cush S et al. Evidence-based study design for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. J Infect Dis 2019; 10: 1536–44. - PMC - PubMed
    1. Borgatta B, Gattarello S, Mazo CA et al. The clinical significance of pneumonia in patients with respiratory specimens harbouring multidrug-resistant Pseudomonas aeruginosa: a 5-year retrospective study following 5667 patients in four general ICUs. Eur J Clin Microbiol Infect Dis 2017; 36: 2155–63. - PubMed
    1. Tedja R, Nowacki A, Fraser T et al. The impact of multidrug resistance on outcomes in ventilator-associated pneumonia. Am J Infect Control 2014; 42: 542–5. - PubMed

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