Pharmacokinetics and Dosing of Ceftobiprole Medocaril for the Treatment of Hospital- and Community-Acquired Pneumonia in Different Patient Populations.
Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are among the most common infections treated in the hospital setting, and together they place a significant burden on healthcare systems. Successful management of HAP and CAP depends on rapid initiation of empirical antibiotic therapy with broad-spectrum antibiotics. Ceftobiprole is a new-generation, broad-spectrum cephalosporin antibiotic for the treatment of HAP (excluding ventilator-associated pneumonia) and CAP. It displays potent in vitro activity against a broad range of pathogens important in pneumonia. This review summarizes the pharmacokinetic profile of ceftobiprole, and considers the pharmacokinetic parameters and pharmacodynamics underlying the choice of dosing regimen. Ceftobiprole shows linear pharmacokinetics after single and multiple doses and is eliminated predominantly through the kidneys. Ceftobiprole is administered as a 500 mg intravenous infusion over 2 h every 8 h, and steady-state concentrations are reached on the first day of dosing. Dose adjustment is recommended for patients with moderate or severe renal impairment and for those with end-stage renal disease. Extending the infusion time of ceftobiprole to 4 h is recommended to optimize drug exposure in critically ill patients with augmented renal clearance. However, there is no need for dose adjustments based on age, sex or ethnicity, or for patients with severe obesity. Population pharmacokinetic modelling and Monte Carlo simulations were used to determine the optimal dosing regimen for ceftobiprole in special patient populations, including paediatric patients. Future studies of ceftobiprole in patients with HAP and CAP would be of interest.
Department of Pulmonology, Hospital Clinic of Barcelona, CIBERES, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain. atorres@ub.edu.
Antonio
A
Torres
Erasmus MC, Rotterdam, The Netherlands.|Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
Johan Willem
JW
Mouton
Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy.|Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
Federico
F
Pea
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000188:drug therapy; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010372:Pediatrics; D011014:Pneumonia / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C505439:ceftobiprole medocaril