Ceftaroline

Ceftaroline (given as the prodrug ceftaroline fosamil) is an anti-MRSA cephalosporin used for skin and soft tissue infection and community-acquired pneumonia, and in specialist salvage regimens for persistent MRSA bacteraemia.

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

Mechanism. Binds penicillin-binding protein 2a of MRSA and the altered proteins of penicillin-resistant pneumococci, as well as other penicillin-binding proteins; hydrolysed by ESBL and AmpC enzymes.

Spectrum. MSSA, MRSA, vancomycin-intermediate strains, penicillin-resistant pneumococci, streptococci, Haemophilus, Moraxella and non-ESBL Enterobacterales. Not active against Pseudomonas, Acinetobacter, Enterococcus faecium, ESBL producers or most anaerobes.

Pharmacokinetics. IV only; the prodrug converts rapidly to active ceftaroline. Half-life about 2.5 hours. Protein binding about 20%. About 88% eliminated by the kidney. Limited CSF data.

No loading dose. Availability in East Africa is limited.

Adults.

• Acute bacterial skin and skin structure infection: 600 mg IV every 12 hours for 5 to 14 days.
• Community-acquired bacterial pneumonia: 600 mg IV every 12 hours for 5 to 7 days.
• Complicated skin infection with Staphylococcus aureus of raised MIC (EU labelling): 600 mg every 8 hours as a 2-hour infusion.
• Persistent MRSA bacteraemia or endocarditis (off-label, specialist use): 600 mg IV every 8 hours, usually combined with another agent.

Children (licensing varies).

• Under 2 years: 8 mg/kg every 8 hours.
• 2 years and over under 33 kg: 12 mg/kg every 8 hours.
• 33 kg or more: 400 mg every 8 hours or 600 mg every 12 hours.
• Neonates (birth to under 2 months): 6 mg/kg every 8 hours.

Alternatives. Vancomycin, linezolid, daptomycin (not for pneumonia), teicoplanin, ceftobiprole.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, nausea, rash, headache, phlebitis, raised liver enzymes. Serious: anaphylaxis, severe skin reactions, Clostridioides difficile infection, direct Coombs test conversion in about 10% (haemolytic anaemia is rare), neutropenia and agranulocytosis in prolonged courses, hypokalaemia, seizures in renal failure.

Interactions. No clinically important cytochrome P450 interactions. Nephrotoxic drugs may add to renal risk.

Common prescribing errors. Using it for Pseudomonas, enterococcal or ESBL infection, and omitting renal dose adjustment.

Special groups.

• Pregnancy and breastfeeding: limited data; use only if the benefit outweighs unknown risk.
• Older adults: adjust by kidney function.
• Kidney impairment: creatinine clearance over 50 mL/min no change; 30 to 50 mL/min 400 mg every 12 hours; 15 to 29 mL/min 300 mg every 12 hours; under 15 mL/min or haemodialysis 200 mg every 12 hours (given after dialysis on dialysis days).
• Liver impairment: no adjustment.

Preparation. Reconstitute each 600 mg vial with 20 mL water for injection, then dilute in 250 mL of 0.9% sodium chloride or 5% glucose. Infuse over 5 to 60 minutes (2 hours in the 8-hourly regimen).

Baseline and monitoring. - Baseline: allergy history, cultures, creatinine, full blood count. - During treatment: creatinine twice weekly; full blood count weekly in courses over 14 days; direct Coombs test if unexplained anaemia. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, haemolysis, agranulocytosis or severe diarrhoea.

Referral and escalation. Infectious diseases advice is needed for MRSA bacteraemia, endocarditis, bone infection and any off-label use.