Vancomycin

Vancomycin is a glycopeptide antibiotic and the usual first-line intravenous drug for MRSA bloodstream, bone, joint, skin and lung infection, and for serious infection with ampicillin-resistant enterococci and coagulase-negative staphylococci. Orally it acts locally in the gut for Clostridioides difficile infection.

Classification. Glycopeptide.

Mechanism. Binds the D-alanyl-D-alanine terminus of cell wall precursors and blocks peptidoglycan polymerisation. Killing is slow and depends on exposure over time (AUC to MIC ratio).

Spectrum. MRSA, MSSA (less effective than beta-lactams), coagulase-negative staphylococci, streptococci, pneumococci including penicillin-resistant strains, Enterococcus faecalis and Corynebacterium. Not active against vancomycin-resistant enterococci, Gram-negative bacilli or anaerobes except Clostridioides difficile.

Pharmacokinetics. Poor oral absorption except in severe colitis or renal failure. IV half-life 4 to 6 hours, up to 7 days in renal failure. Protein binding about 50%. More than 80% excreted unchanged in urine. Poor CSF penetration unless the meninges are inflamed.

Dose by actual body weight. Titration is by AUC (preferred) or trough concentration, and by kidney function.

Adults, IV.

• Loading dose in serious infection (bacteraemia, endocarditis, meningitis, severe pneumonia, sepsis): 20 to 35 mg/kg actual body weight, usually capped at 3 g.
• Maintenance: 15 to 20 mg/kg every 8 to 12 hours with normal kidney function. Maximum single dose 2 g.
• Targets: daily AUC 400 to 600 mg·h/L (assuming a vancomycin MIC of 1 mg/L).
• Trough targets of 10 to 15 mg/L are used when AUC is unavailable. Troughs of 15 to 20 mg/L raise nephrotoxicity. Reserve them for severe CNS or deep infection where AUC cannot be estimated.
• Durations: MRSA bacteraemia at least 14 days from first negative culture (4 to 6 weeks if complicated), native valve endocarditis 6 weeks, bone and joint infection 6 weeks or longer, pneumonia 7 to 21 days, skin and soft tissue infection 7 to 14 days.
• Surgical prophylaxis (beta-lactam allergy or MRSA colonisation): 15 mg/kg (maximum 2 g) infused to finish within 120 minutes before incision.

Adults, oral (Clostridioides difficile infection).

• Initial episode: 125 mg every 6 hours for 10 days (fidaxomicin is preferred when available).
• Fulminant infection: 500 mg every 6 hours by mouth or nasogastric tube, with metronidazole 500 mg IV every 8 hours. If ileus, add 500 mg in 100 mL of 0.9% sodium chloride rectally every 6 hours.
• Recurrence: tapered and pulsed regimen under specialist direction.

Children. Loading 20 mg/kg. Maintenance 15 mg/kg every 6 hours (60 mg/kg/day) in severe infection with AUC or level monitoring. Neonates 10 to 15 mg/kg every 8 to 24 hours depending on gestation and postmenstrual age.

Alternatives. Teicoplanin, linezolid, daptomycin (not for pneumonia), ceftaroline, flucloxacillin or cefazolin for MSSA.

Contraindications. Hypersensitivity to vancomycin.

Adverse effects.

• Infusion reaction (flushing, erythema, pruritus, hypotension) from histamine release when infused too fast.
• Nephrotoxicity, most with high troughs, critical illness and co-administered piperacillin tazobactam, aminoglycosides, loop diuretics, contrast and amphotericin.
• Ototoxicity (uncommon), neutropenia and thrombocytopenia in courses over 2 weeks, drug fever, rash, DRESS, linear IgA bullous dermatosis, phlebitis.

Interactions. Nephrotoxic and ototoxic drugs. Neuromuscular blockers (prolonged block). Oral vancomycin can raise INR in patients on warfarin.

Common prescribing errors. Omitting a loading dose in sepsis, rapid infusion, using trough levels of 15 to 20 mg/L routinely, no repeat level when kidney function changes, and using it for MSSA when a beta-lactam is possible.

Special groups.

• Pregnancy: use if needed, with level monitoring. Breastfeeding: compatible.
• Older adults: reduce by kidney function. Ototoxicity risk is higher.
• Kidney impairment: give the full loading dose, then set maintenance by levels or AUC.
• Haemodialysis: 15 to 25 mg/kg loading dose after the session, then 5 to 10 mg/kg after each session set by pre-dialysis levels (target 15 to 20 mg/L).
• Liver impairment: no adjustment.
• Obesity: load by actual weight capped at 3 g. Set maintenance by AUC rather than fixed doses.
• Region: MRSA prevalence differs between East African hospitals, and levels are not always available. Use renal-adjusted dosing, avoid prolonged high doses and monitor creatinine closely.

Preparation. Dilute to 5 mg/mL or less in 0.9% sodium chloride or 5% glucose (up to 10 mg/mL through a central line when fluid is restricted). Infuse at 10 mg/min or slower, so 1 g takes at least 60 minutes. Oral solution can be made from the IV powder.

Baseline and monitoring.

• Baseline: creatinine, weight, full blood count, cultures, hearing history.
• During treatment: AUC or trough before the fourth dose and again after any change in kidney function.
• Creatinine 2 to 3 times weekly (daily in unstable patients). Full blood count weekly. Hearing in prolonged courses.
• Stop and reassess if creatinine rises by more than 0.3 mg/dL (26 micromol/L) in 48 hours.

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

Referral and escalation. Infectious diseases for MRSA bacteraemia, endocarditis, prosthetic material infection and persistent positive cultures at 72 hours.