Ceftolozane Tazobactam

Ceftolozane tazobactam combines a cephalosporin with strong antipseudomonal activity and a beta-lactamase inhibitor. It is a reserve agent for multidrug-resistant Pseudomonas aeruginosa and for ESBL-producing Enterobacterales in complicated infection.

Classification. Beta-lactam, novel cephalosporin plus penicillanic acid sulphone inhibitor. Doses are written as the combined weight: 1.5 g contains 1 g ceftolozane and 0.5 g tazobactam.

Mechanism. Ceftolozane blocks penicillin-binding proteins and resists AmpC and efflux; tazobactam inhibits many ESBLs.

Spectrum. Pseudomonas aeruginosa (including many strains resistant to piperacillin tazobactam, ceftazidime and carbapenems), ESBL-producing Enterobacterales, streptococci. Not active against KPC and metallo-beta-lactamase producers, Acinetobacter, staphylococci, Enterococcus or most anaerobes.

Pharmacokinetics. IV only. Half-life about 3 hours for ceftolozane. Protein binding about 20%. Over 90% excreted unchanged in urine.

Reserve agent; specialist use. No loading dose.

Adults. - Complicated intra-abdominal infection: 1.5 g IV over 1 hour every 8 hours, with metronidazole 500 mg every 8 hours, for 4 to 14 days. - Complicated urinary tract infection and pyelonephritis: 1.5 g over 1 hour every 8 hours for 7 days. - Hospital-acquired and ventilator-associated pneumonia: 3 g (2 g/1 g) over 1 hour every 8 hours for 8 to 14 days. - Difficult-to-treat Pseudomonas aeruginosa infection (specialist): 3 g every 8 hours is often used for bacteraemia and pneumonia.

Children (limited licensing). 20 mg/kg ceftolozane (with 10 mg/kg tazobactam) every 8 hours for complicated intra-abdominal and urinary infection; check the maximum a dose in the local label.

Alternatives. Ceftazidime avibactam, imipenem cilastatin relebactam, cefiderocol, colistin-based regimens.

Contraindications. Hypersensitivity to ceftolozane, tazobactam, other beta-lactamase inhibitors, or any cephalosporin or penicillin.

Adverse effects. Nausea, diarrhoea, constipation, headache, pyrexia, raised liver enzymes. Serious: anaphylaxis, Clostridioides difficile infection, severe skin reactions, interstitial nephritis, neurotoxicity in renal failure.

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

Common prescribing errors. Omitting metronidazole in intra-abdominal infection, using the lower dose for pneumonia, and using it for KPC or metallo-beta-lactamase producers.

Special groups. - Pregnancy and breastfeeding: limited data; use only if the benefit outweighs unknown risk. - Older adults: adjust by kidney function. - Kidney impairment, 1.5 g regimen: creatinine clearance 30 to 50 mL/min 750 mg every 8 hours; 15 to 29 mL/min 375 mg every 8 hours; haemodialysis a single 750 mg loading dose then 150 mg every 8 hours, given after the session on dialysis days.

Pneumonia 3 g regimen: 30 to 50 mL/min 1.5 g every 8 hours; 15 to 29 mL/min 750 mg every 8 hours; haemodialysis 450 mg loading dose then 90 mg every 8 hours. - Liver impairment: no adjustment. - Region: availability in East Africa is limited.

Preparation. Reconstitute each 1.5 g vial with 10 mL water for injection or 0.9% sodium chloride, then dilute in 100 mL of 0.9% sodium chloride or 5% glucose and infuse over 1 hour. Store unopened vials refrigerated.

Baseline and monitoring. - Baseline: allergy history, cultures with susceptibility testing, creatinine, full blood count. - During treatment: creatinine twice weekly (dose changes needed as function changes); liver tests weekly. - No therapeutic drug monitoring.

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

Referral and escalation. Infectious diseases involvement before use and when there is treatment failure.