Ticarcillin Clavulanate

Ticarcillin clavulanate is an antipseudomonal carboxypenicillin combined with a beta-lactamase inhibitor. It has been withdrawn from many markets and replaced by piperacillin tazobactam, but it still appears in some formularies and in older treatment plans.

Classification. Beta-lactam, carboxypenicillin plus clavulanic acid. Doses are written as the combined weight: 3.1 g contains 3 g ticarcillin and 0.1 g clavulanic acid.

Mechanism. Ticarcillin blocks penicillin-binding proteins; clavulanic acid inactivates many class A beta-lactamases, including those of Staphylococcus aureus, Haemophilus, Bacteroides and many Enterobacterales.

Spectrum. MSSA, streptococci, Enterobacterales, Pseudomonas aeruginosa (less active than piperacillin), anaerobes including Bacteroides fragilis and Stenotrophomonas maltophilia (variable). Not active against MRSA, Enterococcus faecium or ESBL and carbapenemase producers.

Pharmacokinetics. IV only. Half-life about 1 hour; renal elimination of ticarcillin 85%. Clavulanate is metabolised and also renally cleared. Limited CSF penetration.

Availability is limited, so confirm the product before prescribing. No loading dose. Maximum 24 g ticarcillin (about 24.8 g of the combination) daily in adults.

Adults. 3.1 g IV every 4 to 6 hours for moderate to severe infection (lower respiratory, intra-abdominal, gynaecological, skin and bone). Severe or Pseudomonas infection: 3.1 g every 4 hours, often with an aminoglycoside given separately. Duration depends on site, usually 5 to 14 days.

Children 3 months and over under 60 kg. 200 mg/kg/day ticarcillin in divided doses every 6 hours for mild to moderate infection; 300 mg/kg/day every 4 hours for severe infection.

Alternatives. Piperacillin tazobactam, meropenem, cefepime, ceftazidime.

Contraindications. Penicillin or clavulanate hypersensitivity; history of clavulanate-associated cholestatic jaundice.

Adverse effects. Diarrhoea, rash, thrombophlebitis. Serious: anaphylaxis, bleeding from platelet dysfunction (more with renal failure), hypokalaemia, hypernatraemia and volume overload from the large sodium load, cholestatic hepatitis from clavulanate, cytopenias, seizures in renal failure and Clostridioides difficile infection.

Interactions. Aminoglycosides are inactivated in the same bag; methotrexate toxicity; probenecid raises levels; anticoagulants and antiplatelet drugs increase bleeding risk; warfarin INR rise.

Common prescribing errors. Not reducing the dose in renal failure, mixing with gentamicin and omitting potassium and sodium monitoring.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by renal function. - Kidney impairment: creatinine clearance 30 to 60 mL/min 2 g ticarcillin every 4 hours; 10 to 30 mL/min 2 g every 8 hours; under 10 mL/min 2 g every 12 hours (every 24 hours if liver dysfunction coexists). Haemodialysis: 2 g every 12 hours with 3.1 g after each session. - Liver impairment: caution; clavulanate hepatotoxicity.

Preparation. Reconstitute and dilute as the label directs; infuse over 30 minutes. Sodium content is high, roughly 4.5 to 5 mmol in each gram.

Baseline and monitoring. - Baseline: allergy history, cultures, creatinine, sodium, potassium, full blood count, liver tests. - During treatment: electrolytes and creatinine at least twice weekly, platelet count and clotting if bleeding, liver tests weekly. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, bleeding, jaundice or unexplained cytopenia.

Referral and escalation. Seek infectious diseases advice for Pseudomonas infection, failure to respond, and when switching to current alternatives.