Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie
Grantová podpora
U19 AI135964
NIAID NIH HHS - United States
PubMed
34380538
PubMed Central
PMC8356211
DOI
10.1186/s13054-021-03694-3
PII: 10.1186/s13054-021-03694-3
Knihovny.cz E-zdroje
- Klíčová slova
- All-cause mortality, Clinical response, ESBL, HABP/VABP, Mechanical ventilation, Multivariable analysis, Nosocomial pneumonia, Pseudomonas aeruginosa,
- MeSH
- antibakteriální látky farmakologie normy terapeutické užití MeSH
- bakteriální pneumonie farmakoterapie MeSH
- cefalosporiny farmakologie normy terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- hodnocení ekvivalence jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- meropenem farmakologie normy terapeutické užití MeSH
- nozokomiální pneumonie farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tazobaktam farmakologie normy terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antibakteriální látky MeSH
- cefalosporiny MeSH
- ceftolozane, tazobactam drug combination MeSH Prohlížeč
- meropenem MeSH
- tazobaktam MeSH
BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.
Departamento de Clínica Médica Universidade Federal do Paraná Curitiba Brazil
Department of Anaesthesia and Intensive Care General Hospital of Kolin Kolin Czech Republic
Department of Emergency and Critical Care Medicine Hiroshima University Hiroshima Japan
Hospital Clinic Universitat de Barcelona IDIBAPS CIBERES Barcelona Spain
Intensive Care Medicine Department Université Paris Diderot Paris France
MRL Merck and Co Inc Kenilworth NJ USA
Pulmonology Centre North Estonia Medical Centre Tallinn Estonia
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ClinicalTrials.gov
NCT02070757