ArticleAntimicrobial agents and chemotherapy2009
Identifying exposure targets for treatment of staphylococcal pneumonia with ceftobiprole.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- Pulmonary penetration of piperacillin and tazobactam in critically ill patients.Clinical pharmacology and therapeutics · 2014Trial
- Pulmonary Pharmacokinetics/Pharmacodynamics of Commonly Used Antibiotics in the Treatment of Community-Acquired Pneumonia.European journal of drug metabolism and pharmacokinetics · 2026Review
- Development and confirmation of humanized plasma and epithelial lining fluid exposures of meropenem, cefiderocol and tobramycin in a standardized neutropenic murine pneumonia model.The Journal of antimicrobial chemotherapy · 2025Article
- Establishment of a diverse pheno-genotypic challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa suitable for use in the murine pneumonia model.The Journal of antimicrobial chemotherapy · 2025Article
- Quantitative performance of humanized serum and epithelial lining fluid exposures of tigecycline and levofloxacin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model.The Journal of antimicrobial chemotherapy · 2024Article
- Pharmacokinetic/pharmacodynamic analysis of sulbactam againstJAC-antimicrobial resistance · 2024Article
- Real-World Experience of Ceftobiprole for Community- and Hospital-Acquired Pneumonia from a Stewardship Perspective.Microorganisms · 2024Article
- Lessons Are Still Being Learned about Intrapulmonary Antibiotic Concentrations.American journal of respiratory and critical care medicine · 2024Article
- New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Targeted Therapy of Severe Infections Caused byMicroorganisms · 2023Article
- Pharmacodynamic Thresholds for Beta-Lactam Antibiotics: A Story of MouseFrontiers in pharmacology · 2022Review
- Article
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management.Microorganisms · 2021Review
- Ceftobiprole Perspective: Current and Potential Future Indications.Antibiotics (Basel, Switzerland) · 2021Review
- New cephalosporins for the treatment of pneumonia in internal medicine wards.Journal of thoracic disease · 2020Review
- Selecting the dosage of ceftazidime-avibactam in the perfect storm of nosocomial pneumonia.European journal of clinical pharmacology · 2020Review
- Ceftobiprole for the treatment of pneumonia.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- Ceftobiprole: pharmacokinetics and PK/PD profile.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms.Microorganisms · 2019Review
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ceftobiprole is a cephalosporin with potent activity against methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). In order to treat patients with severe staphylococcal pneumonia, it is important to understand the drug exposure required to mediate the killing of multiple log(10) cells in a preclinical-infection model. We measured drug exposure in terms of the percentage of penetration of the drug into epithelial lining fluid (ELF) and in terms of the time for which the drug concentration was above the MIC (time>MIC) in plasma and ELF. In a murine model of staphylococcal pneumonia, we demonstrated that ceftobiprole penetrated into ELF from the plasma at a median level of nearly 69% (25th to 75th percentile range, 25 to 187%), as indexed to the ratio of values for the area under the concentration-time curve in ELF and plasma. The total-drug times>MIC in ELF that were required to kill 1 log(10) and 2 log(10) CFU/g of lung tissue were 15% and 25% of the dosing interval. We also examined the penetration of ELF by ceftobiprole in volunteers, demonstrating mean and median penetration percentages of 25.5% and 15.3%, respectively (25th to 75th percentile range, 8 to 30%). Attainment rates were calculated for kill targets of 1 log(10) and 2 log(10) CFU/g, taken from the murine model, but using the volunteer ceftobiprole ELF penetration data. The standard dose for ceftobiprole is 0.5 g every 8 h as a 2-h infusion. The attainment rates remained above 90% for 1-log(10) and 2-log(10) CFU/g kill targets at MICs of 1 and 0.5 mg/liter, respectively. Taking the expectation over the distribution of ceftobiprole MICs for 4,958 MRSA isolates showed an overall target attainment of 85.6% for a 1-log(10) CFU/g kill and 79.7% for a 2-log(10) CFU/g kill. It is important to derive exposure targets in preclinical-infection models of the infection site so that these targets can be explored in clinical trials in order to optimize the probability of a good clinical outcome.
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