Telavancin

Telavancin is a lipoglycopeptide with dual action on cell wall synthesis and membrane integrity. It is a reserve option for complicated skin infection and hospital-acquired pneumonia caused by MRSA, limited by nephrotoxicity and foetal risk.

Classification. Lipoglycopeptide.

Mechanism. Blocks peptidoglycan synthesis and depolarises the bacterial membrane.

Spectrum. MRSA, MSSA, streptococci, vancomycin-susceptible enterococci, some vancomycin-intermediate staphylococci. Not active against Gram-negative bacilli.

Pharmacokinetics. IV only. Half-life about 8 hours. Protein binding about 90%. About 76% excreted in urine.

Reserve agent; availability in East Africa is very limited. No loading dose. Maximum 10 mg/kg a dose.

Adults. - Complicated skin and skin structure infection: 10 mg/kg IV over 60 minutes every 24 hours for 7 to 14 days. - Hospital-acquired or ventilator-associated pneumonia caused by Staphylococcus aureus, only when no other option is suitable: 10 mg/kg every 24 hours for 7 to 21 days.

Children. Not established.

Alternatives. Vancomycin, linezolid, ceftaroline, teicoplanin, daptomycin.

Boxed-warning level risks. Nephrotoxicity (acute kidney injury more common than with vancomycin), higher mortality in patients with baseline creatinine clearance of 50 mL/min or less in pneumonia studies, and foetal harm in animal studies.

Contraindications. Pregnancy (exclude it before use in people able to conceive and counsel on contraception); hypersensitivity to telavancin; IV unfractionated heparin.

Adverse effects. Taste disturbance (metallic or soapy), nausea, vomiting, foamy urine, headache, infusion reaction, QTc prolongation, raised creatinine.

Coagulation tests. Telavancin falsely prolongs PT, INR, aPTT and ACT for up to 18 hours; draw samples just before the next dose.

Interactions. QT-prolonging drugs; nephrotoxic drugs; ACE inhibitors and diuretics increase kidney injury risk.

Common prescribing errors. Use in pregnancy, use in patients with severe renal impairment, rapid infusion, and routine use as first-line.

Special groups. - Pregnancy: contraindicated. Breastfeeding: avoid unless benefit outweighs risk. - Older adults: monitor kidney function closely. - Kidney impairment: creatinine clearance 30 to 50 mL/min 7.5 mg/kg every 24 hours; 10 to under 30 mL/min 10 mg/kg every 48 hours; avoid in haemodialysis and in pneumonia with creatinine clearance of 50 mL/min or less where alternatives exist. - Liver impairment: no adjustment.

Preparation. Reconstitute with 5% glucose, 0.9% sodium chloride or sterile water, dilute to 0.6 to 8 mg/mL and infuse over 60 minutes.

Baseline and monitoring. - Baseline: pregnancy test, creatinine, ECG, QT-prolonging drug review. - During treatment: creatinine daily to every 2 days; ECG if risk factors; urinalysis.

Stop rules. Stop for creatinine rising by 0.5 mg/dL (44 micromol/L) or 50% over baseline, QT prolongation, pregnancy, or anaphylaxis.

Referral and escalation. Infectious diseases and nephrology input for any acute kidney injury during therapy.