ArticleThe Journal of antimicrobial chemotherapy2020
Lung penetration, bronchopulmonary pharmacokinetic/pharmacodynamic profile and safety of 3 g of ceftolozane/tazobactam administered to ventilated, critically ill patients with pneumonia.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02387372 (A Phase 1, Prospective, Multi-center, Open-label Study to Assess the Plasma Pharmacokinetics and Lung Penetration of Intravenous), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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 Phase 1, Prospective, Multi-center, Open-label Study to Assess the Plasma Pharmacokinetics and Lung Penetration of Intravenous (IV) Ceftolozane/Tazobactam in Critically Ill Patients
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Comparison of Ceftolozane-Tazobactam and Ceftazidime-Avibactam in the Treatment of Multidrug-Resistant/Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Pooled it
- Intrapulmonary penetration of ceftolozane/tazobactam and ceftazidime/avibactam administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial.Critical care (London, England) · 2026Trial
- Probability of Target Attainment Analyses to Inform Ceftolozane/Tazobactam Dosing Regimens for Patients With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia and End-Stage Renal Disease Receiving Intermittent Hemodialysis.Journal of clinical pharmacology · 2023Trial
- 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.The Journal of antimicrobial chemotherapy · 2022Trial
- Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial.Critical care (London, England) · 2021Trial
- Population Pharmacokinetic Analysis for Plasma and Epithelial Lining Fluid Ceftolozane/Tazobactam Concentrations in Patients With Ventilated Nosocomial Pneumonia.Journal of clinical pharmacology · 2021Trial
- Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP).Antimicrobial agents and chemotherapy · 2020Trial
- Comparison of Ceftolozane-Tazobactam Versus Meropenem Regimens in Treating Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-ProducingJournal of clinical medicine · 2026Article
- Pulmonary Pharmacokinetics/Pharmacodynamics of Commonly Used Antibiotics in the Treatment of Community-Acquired Pneumonia.European journal of drug metabolism and pharmacokinetics · 2026Review
- [New antimicrobial substances to combat increasing resistance].Innere Medizin (Heidelberg, Germany) · 2026Review
- Clinical Outcomes and Predictors of Mortality in Patients with Difficult-to-Treat ResistantAntibiotics (Basel, Switzerland) · 2026Article
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- Towards a holistic approach to pulmonary infections. Insights from the Sixth Annual Meeting of Spanish Experts 2024.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2025Review
- Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors?Antimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetic/pharmacodynamic analysis of sulbactam againstJAC-antimicrobial resistance · 2024Article
- Novel Antibiotics for Gram-Negative Nosocomial Pneumonia.Antibiotics (Basel, Switzerland) · 2024Review
- Identifying and mathematically modeling the time-course of extracellular metabolic markers associated with resistance to ceftolozane/tazobactam inAntimicrobial agents and chemotherapy · 2024Article
- Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.Future microbiology · 2024Review
- Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review.Frontiers in antibiotics · 2024Review
- Ceftolozane-Tazobactam against Pseudomonas aeruginosa Cystic Fibrosis Clinical Isolates in the Hollow-Fiber Infection Model: Challenges Imposed by Hypermutability and Heteroresistance.Antimicrobial agents and chemotherapy · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCeftolozane/tazobactam is approved for hospital-acquired/ventilator-associated bacterial pneumonia at double the dose (i.e. 2 g/1 g) recommended for other indications. We evaluated the bronchopulmonary pharmacokinetic/pharmacodynamic profile of this 3 g ceftolozane/tazobactam regimen in ventilated pneumonia patients.
methodsThis was an open-label, multicentre, Phase 1 trial (clinicaltrials.gov: NCT02387372). Mechanically ventilated patients with proven/suspected pneumonia received four to six doses of 3 g of ceftolozane/tazobactam (adjusted for renal function) q8h. Serial plasma samples were collected after the first and last doses. One bronchoalveolar lavage sample per patient was collected at 1, 2, 4, 6 or 8 h after the last dose and epithelial lining fluid (ELF) drug concentrations were determined. Pharmacokinetic parameters were estimated by non-compartmental analysis and pharmacodynamic analyses were conducted to graphically evaluate achievement of target exposures (plasma and ELF ceftolozane concentrations >4 mg/L and tazobactam concentrations >1 mg/L; target in plasma: ≥30% and ≥20% of the dosing interval, respectively).
resultsTwenty-six patients received four to six doses of study drug; 22 were included in the ELF analyses. Ceftolozane and tazobactam Tmax (6 and 2 h, respectively) were delayed in ELF compared with plasma (1 h). Lung penetration, expressed as the ratio of mean drug exposure (AUC) in ELF to plasma, was 50% (ceftolozane) and 62% (tazobactam). Mean ceftolozane and tazobactam ELF concentrations remained >4 mg/L and >1 mg/L, respectively, for 100% of the dosing interval. There were no deaths or adverse event-related study discontinuations.
conclusionsIn ventilated pneumonia patients, 3 g of ceftolozane/tazobactam q8h yielded ELF exposures considered adequate to cover ceftolozane/tazobactam-susceptible respiratory pathogens.
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