Teicoplanin

Teicoplanin is a glycopeptide with a very long half-life, allowing once-daily or intramuscular dosing. It is used for MRSA and other Gram-positive infection when vancomycin is not tolerated or when outpatient treatment is planned.

Classification. Glycopeptide.

Mechanism. Binds the D-alanyl-D-alanine terminus of cell wall precursors and blocks peptidoglycan polymerisation.

Spectrum. MRSA, MSSA, coagulase-negative staphylococci (some resistance), streptococci, pneumococci, Enterococcus faecalis and Clostridioides difficile. Not active against vanA vancomycin-resistant enterococci, Gram-negative bacilli or most anaerobes.

Pharmacokinetics. IV or IM. Half-life 70 to 100 hours. Protein binding about 90%. About 80% excreted unchanged in urine. Poor CSF penetration.

Loading doses are essential. Availability differs between regions (it is not marketed in the United States).

Adults, IV or IM.

• Loading: 6 mg/kg (usually 400 mg) every 12 hours for 3 doses in moderate infection; 12 mg/kg (usually 800 mg) every 12 hours for 3 to 5 doses in severe infection, bone and joint infection and endocarditis.
• Maintenance: 6 mg/kg once daily in moderate infection; 12 mg/kg once daily in severe infection, bone and joint infection and endocarditis.
• Trough targets: more than 10 mg/L for most infections and 15 to 30 mg/L for endocarditis and bone and joint infection (HPLC); fluorescence immunoassay values are higher, so confirm with the laboratory.
• Durations: bacteraemia at least 14 days; endocarditis 6 weeks; bone and joint 6 weeks or longer.
• Surgical prophylaxis: 400 mg IV once at induction.

Children 2 months and over. Loading 10 mg/kg every 12 hours for 3 doses; maintenance 6 to 10 mg/kg once daily (10 mg/kg in severe infection). Neonates: loading 16 mg/kg on day 1, then 8 mg/kg once daily.

Alternatives. Vancomycin, linezolid, daptomycin, ceftaroline.

Contraindications. Hypersensitivity to teicoplanin. Cross-reaction with vancomycin allergy can occur but red man-type reaction is not a contraindication.

Adverse effects. Injection-site pain and phlebitis, rash, fever, raised liver enzymes. Serious: thrombocytopenia and neutropenia (especially at high dose), nephrotoxicity (less than vancomycin), ototoxicity, anaphylaxis, severe cutaneous reactions.

Interactions. Aminoglycosides, loop diuretics and ciclosporin increase nephrotoxicity and ototoxicity; neuromuscular blockers.

Common prescribing errors. Omitting loading doses, under-dosing bone and joint infection and endocarditis, and not reducing the dose after day 4 in renal impairment.

Special groups. - Pregnancy: use only if the benefit outweighs risk. Breastfeeding: limited data. - Older adults: reduce by kidney function. - Kidney impairment: give full loading doses and for the first 3 days the usual maintenance dose. From day 4, with creatinine clearance 40 to 60 mL/min give half the maintenance dose daily or the full dose every 48 hours; under 40 mL/min and in haemodialysis give one third of the dose daily or the full dose every 72 hours. It is not removed by dialysis. - Liver impairment: no adjustment.

Preparation. Add diluent slowly, roll the vial gently and do not shake (foaming). IV: inject over 3 to 5 minutes (loading doses by infusion over 30 minutes). IM: maximum 3 mL at one site.

Baseline and monitoring. - Baseline: creatinine, full blood count, liver tests, hearing history, cultures. - During treatment: trough level after the loading phase and weekly thereafter; full blood count and creatinine weekly (twice weekly with high dose); hearing in prolonged courses.

Stop rules. Stop for anaphylaxis, severe cytopenia, severe skin reaction or acute kidney injury attributed to the drug.

Referral and escalation. Infectious diseases for bacteraemia, endocarditis and implant infection.