Ceftazidime

Ceftazidime is a parenteral third-generation cephalosporin with strong antipseudomonal activity but limited Gram-positive cover. It is used for Pseudomonas infection, febrile neutropenia, melioidosis and hospital-acquired Gram-negative sepsis.

Classification. Beta-lactam, third-generation cephalosporin.

Mechanism. Blocks penicillin-binding proteins; stable to many beta-lactamases but hydrolysed by ESBL and AmpC enzymes.

Spectrum. Pseudomonas aeruginosa, Burkholderia pseudomallei, Enterobacterales without ESBL or AmpC hyperproduction, Haemophilus, Neisseria. Weak against staphylococci, streptococci (including pneumococci), enterococci and anaerobes.

Pharmacokinetics. IV or IM. Half-life 1.5 to 2 hours. Protein binding under 10%. Over 80% excreted unchanged in urine. CSF penetration is adequate in meningitis.

No loading dose except in continuous infusion. Maximum 6 g daily in adults (up to 9 g in cystic fibrosis with specialist direction).

Adults.

• Moderate infection: 1 g IV every 8 hours.
• Severe infection, Pseudomonas, nosocomial pneumonia: 2 g IV every 8 hours.
• Febrile neutropenia: 2 g IV every 8 hours.
• Pseudomonas meningitis: 2 g IV every 8 hours for 21 days.
• Melioidosis, intensive phase: 2 g IV every 6 to 8 hours (50 mg/kg, maximum 2 g a dose) for at least 10 to 14 days, then eradication therapy with co-trimoxazole for 3 to 6 months.
• Continuous infusion: loading dose 2 g, then 4 to 6 g over 24 hours.

Children 1 month to 17 years. 30 to 50 mg/kg every 8 hours (maximum 6 g daily); neutropenia and Pseudomonas 50 mg/kg every 8 hours.

Neonates. 25 to 50 mg/kg every 12 hours.

Alternatives. Cefepime, piperacillin tazobactam, meropenem, ciprofloxacin.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, rash, phlebitis, eosinophilia, raised liver enzymes, Clostridioides difficile infection. Serious: anaphylaxis, severe skin reactions, haemolytic anaemia, neutropenia, interstitial nephritis, neurotoxicity (myoclonus, confusion, non-convulsive status epilepticus) in renal failure.

Interactions. Probenecid; loop diuretics and aminoglycosides (nephrotoxicity); warfarin INR rise; chloramphenicol antagonism (in vitro); oral typhoid vaccine.

Common prescribing errors. Using it as monotherapy for staphylococcal or pneumococcal infection, not reducing dose in renal failure and assuming ESBL cover.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function; watch for confusion. - Kidney impairment (after an initial 1 to 2 g dose): creatinine clearance 31 to 50 mL/min 1 g every 12 hours; 16 to 30 mL/min 1 g every 24 hours; 6 to 15 mL/min 500 mg every 24 hours; 5 mL/min or less 500 mg every 48 hours. Haemodialysis: 1 g after each session. - Liver impairment: no adjustment.

Preparation. IV bolus: dissolve 1 g in 10 mL water for injection and inject over 3 to 5 minutes. Infusion: dilute in 50 to 100 mL of 0.9% sodium chloride or 5% glucose over 20 to 30 minutes. IM: reconstitute with 1% lidocaine.

Baseline and monitoring. - Baseline: allergy history, cultures, creatinine, full blood count. - During treatment: creatinine and neurological status daily in renal impairment; full blood count twice weekly. - No routine therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, cytopenia or neurotoxicity.

Referral and escalation. Infectious diseases for Pseudomonas bacteraemia, melioidosis, cystic fibrosis and neutropenic sepsis.