Ceftobiprole

Ceftobiprole (given as the prodrug ceftobiprole medocaril) is an advanced-generation cephalosporin active against MRSA, penicillin-resistant pneumococci and Pseudomonas. It is used for hospital-acquired and community-acquired pneumonia, skin infection and, in some regions, Staphylococcus aureus bacteraemia.

Classification. Beta-lactam, advanced-generation (fifth-generation) cephalosporin.

Mechanism. Binds penicillin-binding protein 2a of MRSA and other proteins; stable against many beta-lactamases but hydrolysed by ESBL and carbapenemase enzymes.

Spectrum. MSSA, MRSA, penicillin-resistant pneumococci, Enterococcus faecalis, Haemophilus, Pseudomonas aeruginosa and non-ESBL Enterobacterales. Not reliable against Enterococcus faecium, Acinetobacter, ESBL producers or anaerobes.

Pharmacokinetics. IV only; the prodrug converts rapidly to active ceftobiprole. Half-life about 3 hours. Protein binding about 16%. About 89% excreted unchanged in urine.

No loading dose. Availability in East Africa is limited and labels differ between regions.

Adults. - Community-acquired pneumonia and hospital-acquired pneumonia (excluding ventilator-associated): 500 mg IV every 8 hours as a 2-hour infusion. Duration: community-acquired 5 to 7 days; hospital-acquired 7 to 14 days. - Acute bacterial skin and skin structure infection: 500 mg IV every 8 hours as a 2-hour infusion for 5 to 14 days. - Staphylococcus aureus bacteraemia (regional labelling): 500 mg every 6 hours for the first 8 days, then every 8 hours, as 2-hour infusions, for at least 14 days.

Children. Weight-banded dosing exists in some labels; use specialist advice.

Alternatives. Ceftaroline, vancomycin, linezolid, teicoplanin, daptomycin.

Contraindications. Hypersensitivity to ceftobiprole or any cephalosporin; severe hypersensitivity to penicillins or carbapenems.

Adverse effects. Nausea, vomiting, taste disturbance, diarrhoea, infusion-site reactions, hyponatraemia, rash, raised liver enzymes. Serious: anaphylaxis, severe skin reactions, Clostridioides difficile infection, seizures, haemolytic anaemia.

Interactions. Ceftobiprole inhibits OATP1B1 and OATP1B3 in vitro and may raise statin exposure; use caution with rosuvastatin and similar drugs. It is not metabolised by cytochrome P450.

Common prescribing errors. Giving over 30 minutes instead of 2 hours, omitting renal dose adjustment, and using it for ventilator-associated pneumonia in labelling where this is excluded.

Special groups. - Pregnancy and breastfeeding: insufficient data; avoid unless benefit outweighs risk. - Older adults: adjust by kidney function. - Kidney impairment (EU labelling): creatinine clearance over 50 mL/min no change; 30 to 50 mL/min 500 mg every 12 hours; 15 to 29 mL/min 250 mg every 12 hours; under 15 mL/min or haemodialysis 250 mg every 24 hours. Other regional labels differ. - Liver impairment: no adjustment.

Preparation. Reconstitute each 500 mg vial with 10 mL water for injection or 5% glucose, then dilute in 250 mL of 0.9% sodium chloride or 5% glucose and infuse over 2 hours.

Baseline and monitoring. - Baseline: allergy history, cultures, creatinine, sodium, full blood count. - During treatment: sodium and creatinine twice weekly; liver tests weekly in prolonged courses. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, seizures or severe diarrhoea.

Referral and escalation. Infectious diseases advice is needed for Staphylococcus aureus bacteraemia, hospital-acquired pneumonia and any use outside labelled indications.