ceftobiprole medocaril
Regulatory sources consulted
Approved indications
- Community-acquired and hospital-acquired pneumonia, excluding ventilator-associated pneumonia, and acute bacterial skin and skin-structure infections caused by susceptible organisms.
Contraindications
Absolute
- Hypersensitivity to ceftobiprole medocaril, ceftobiprole, or other cephalosporins.
Clinical warnings
- Major warning · Severe hypersensitivity or anaphylaxis may occur; review beta-lactam allergy history and discontinue if an allergic reaction develops. — CIMA/AEMPS, ficha técnica 78691
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 78691
- Major warning · Accumulation, especially with renal impairment or unadjusted doses, may cause encephalopathy, myoclonus, or seizures; adjust for renal function and monitor neurologic status. — CIMA/AEMPS, ficha técnica 78691
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
During pregnancy, use only when clinically indicated. Assess breastfeeding according to milk exposure and the infant’s condition described in the product information.
Recent literature (PubMed)
Ceftobiprole medocaril is a broad-spectrum 5th-generation cephalosporin with activity against Gram-positives such as methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and against Gram-negatives such as Pseudomonas aeruginosa. The recommended dose is 500 mg every 8 h in 2-hour infusions. Various clinical trials have demonstrated its usefulness in the treatment of community-acquired pneumonia and nosocomial pneumonia, with the exception of ventilator-associated pneumonia. In summary, it is a very useful antibiotic for the treatment of pneumonia.
Drug discovery campaigns often face biopharmaceutical challenges, some of which can be solved by a prodrug approach. Prodrugs are enzymatically or chemically transformed in vivo to produce active drugs. Among these, medoxomil promoieties have been judiciously employed in multiple drug discovery campaigns, leading to three prodrugs gaining FDA approval: azilsartan medoxomil (6), olmesartan medoxomil (20), and ceftobiprole medocaril (29), and one approval in Japan: prulifloxacin (35). The promoiety can be easily appended to mask carboxylic acids, amines, zwitterionic compounds, and other polar groups, imparting lipophilicity to the parent compound. The promoiety has the added advantage of rapid and complete conversion to the parent drug by multiple enzymatic pathways across different tissues. The approach has been used for drugs spanning multiple classes to improve oral bioavailability, solubility, tissue localization, efflux, and side effect profiles. This Perspective analyzes the history and application of medoxomil prodrugs and discusses their potential for drug development.
The objective was to review the pharmacology, efficacy, and safety of intravenous ceftobiprole in the treatment of bloodstream infections, acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP). PubMed and ClinicalTrials.gov were searched using the following terms: ceftobiprole, ceftobiprole medocaril, ceftobiprole medocaril sodium, Zevtera, and BAL5788. Articles published in English between January 1985 and August 15, 2024, related to pharmacology, safety, efficacy, and clinical trials were reviewed. Ceftobiprole has shown similar efficacy to comparator antibiotics in CAP, ABSSSIs, and bloodstream infections. Overall treatment success in patients with bacteremia was 69.8% and 68.7%; 91.3% and 88.1% with ABSSSIs and 86.6% and 87.4% with CAP in ceftobiprole and comparator groups, respectively. Finally, in the management of HAP and VAP, ceftobiprole was inferior in the VAP population. Ceftobiprole had a favorable safety profile with gastrointestinal adverse effects occurring more frequently than comparators.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Clinicians have limited options to treat multidrug-resistant infections. Ceftobiprole has demonstrated efficacy against causative pathogens in specific infections including methicillin-resistant Staphylococcus aureus bacteremia (SAB), ABSSSI, and CAP and may be considered a viable alternative. However, ceftobiprole's impact on HAP, VAP, and febrile neutropenia needs to be further delineated. Ceftobiprole's broad-spectrum activity makes it a viable option for treating patients hospitalized with CAP, ABSSSI, and SAB. Further studies are needed in severely ill HAP or VAP, febrile neutropenia, and pediatric patients.