ceftobiprole-medocaril and Renal-Insufficiency

Ceftobiprole shows many similar pharmacokinetic properties to other cephalosporins, except for not being orally bioactive, and that it is administered by IV infusion as the prodrug ceftobiprole medocaril, which is subsequently hydrolyzed in the blood into the active molecule. Distribution focus in extracellular fluid and active antibiotic concentration has been proven in different corporal tissues using dosing regimen of 500 mg intravenous infusion over 2 h every 8 h. Ceftobiprole is eliminated exclusively into the urine, thus the reason why dose adjustment is required for patients with moderate or severe renal impairment, or increased creatinine clearance. However, there is no need for dose adjustments related with other comorbidities and patients' conditions such as age, body weight. Although considering distribution features, molecular weight and dose fraction, increase dosing regimen might be necessary in patients using renal replacement therapy. The half-life of ceftobiprole is more than 3 h, allowing to easily reach optimal PK/PD parameters with the infusion time of 2 h, using the usual dosing regimen.

Topics: Age Factors; Anti-Bacterial Agents; Area Under Curve; Cephalosporins; Creatinine; Critical Illness; Extracellular Matrix; Half-Life; Humans; Infusions, Intravenous; Kidney; Monte Carlo Method; Obesity; Prodrugs; Renal Insufficiency; Renal Replacement Therapy

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.

Topics: Anti-Bacterial Agents; Area Under Curve; Cephalosporins; Community-Acquired Infections; Critical Illness; Cross Infection; Dose-Response Relationship, Drug; Drug Dosage Calculations; Half-Life; Humans; Infusions, Intravenous; Metabolic Clearance Rate; Microbial Sensitivity Tests; Monte Carlo Method; Pediatrics; Pneumonia; Renal Insufficiency