Trial reportCritical care (London, England)2021
Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial.
Trial report in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02070757 (A Prospective, Randomized, Double-Blind, Multicenter, Phase 3 Study to Assess the Safety and Efficacy of Intravenous Ceftolozane/Tazobactam Compared With Meropenem in Adult Patients With Ventilated Nosocomial Pneumonia), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Prospective, Randomized, Double-Blind, Multicenter, Phase 3 Study to Assess the Safety and Efficacy of Intravenous Ceftolozane/Tazobactam Compared With Meropenem in Adult Patients With Ventilated Nosocomial Pneumonia
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review.The Journal of antimicrobial chemotherapy · 2024Pooled it
- Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem.Critical care (London, England) · 2022Trial
- Exposure-Efficacy Analyses Support Optimal Dosing Regimens of Ceftolozane/Tazobactam in Participants with Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia in ASPECT-NP.Antimicrobial agents and chemotherapy · 2022Trial
- Antimicrobial Pharmacokinetic and Pharmacodynamic Considerations in Special Populations: A Call to Action.Open forum infectious diseases · 2026Review
- Ceftolozane/Tazobactam for Complex and Resistant Infections: Systematic Reviews of Comparative Efficacy Studies.Antibiotics (Basel, Switzerland) · 2026Review
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.Future microbiology · 2024Review
- Anti-Microorganisms · 2023Review
- Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study.Antibiotics (Basel, Switzerland) · 2023Article
- Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial.Annals of intensive care · 2023Article
- Population Pharmacokinetic Modeling of Zaltoprofen in Healthy Adults: Exploring the Dosage Regimen.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Individualized antibiotic dosage regimens for patients with augmented renal clearance.Frontiers in pharmacology · 2023Review
- Drug Dosing in Critically Ill Adult Patients with Augmented Renal Clearance.European journal of drug metabolism and pharmacokinetics · 2022Review
- Drug Regimens of Novel Antibiotics in Critically Ill Patients with Varying Renal Functions: A Rapid Review.Antibiotics (Basel, Switzerland) · 2022Review
- Comparison between meropenem and ceftolozane/tazobactam: possible influence of CRRT.Critical care (London, England) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function.
methodsBaseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit.
resultsA > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [- 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; - 2.6 [- 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; - 2.1 [- 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [- 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [- 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [- 8.7 to 19.0]).
conclusionsC/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.
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