Glycopeptides

Glycopeptides (vancomycin and teicoplanin) are large glycosylated molecules active against Gram-positive bacteria. Vancomycin remains the first-line agent for MRSA, ampicillin-resistant enterococci and beta-lactam-allergic Gram-positive infection; oral vancomycin treats severe C. difficile infection.

Mechanism. Binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors blocks transglycosylation and transpeptidation, and the cell wall fails. Activity is slowly bactericidal and best predicted by the ratio of the 24-hour AUC to MIC (target about 400 or more).

Pharmacokinetics. Not absorbed orally; the oral route acts only in the bowel lumen. IV vancomycin has a half-life of 4 to 6 hours with normal renal function (up to 7 days in anuria), is renally cleared and distributes widely with poor CSF, bone and epithelial lining fluid penetration. Teicoplanin is highly protein-bound with a half-life of 70 to 100 hours.

Spectrum. MRSA and methicillin-resistant coagulase-negative staphylococci, streptococci, E. faecalis, Corynebacterium, Bacillus, Clostridioides difficile (oral). Inactive against Gram-negatives, mycobacteria and vancomycin-resistant enterococci (VanA, VanB).

Resistance. VanA and VanB ligases in enterococci; vancomycin-intermediate S. aureus (thickened wall) and heteroresistant strains; rare VanA in S. aureus.

• Vancomycin: requires level-based dosing, infusion-rate control and renal monitoring; the reference drug for MRSA.
• Teicoplanin: can be given IM or by bolus IV, has a long half-life that allows once-daily dosing, and causes fewer infusion reactions and less nephrotoxicity, but needs a loading period to reach target levels.

Adult regimens (normal renal function).

• Vancomycin IV: loading dose 20 to 35 mg/kg actual body weight (maximum about 3 g) in severe infection, then 15 to 20 mg/kg every 8 to 12 hours. Titrate to an AUC of 400 to 600 mg.h/L; where AUC estimation is not available, a trough of 15 to 20 mg/L is used for serious infection, with the caution that troughs over 15 mg/L carry higher renal risk. Continuous infusion (20 to 30 mg/kg daily after a load, target 20 to 25 mg/L) is an alternative.
• Administration: dilute to no more than 5 mg/mL for peripheral infusion; infuse no faster than 10 mg/min (and at least over 1 hour for 1 g) to avoid vancomycin infusion reaction.
• Oral vancomycin for C. difficile: 125 mg every 6 hours for 10 days in a first episode; fulminant disease 500 mg every 6 hours with intravenous metronidazole, and rectal vancomycin when ileus is present.
• Teicoplanin: loading 6 to 12 mg/kg (400 to 800 mg) every 12 hours for 3 to 5 doses, then 6 to 12 mg/kg once daily; endocarditis and bone infection need trough levels over 20 mg/L.
• Children: vancomycin 15 mg/kg every 6 hours (40 to 60 mg/kg daily) with levels; neonates are dosed by age and renal function.

Selection.

• MRSA bacteraemia, endocarditis, pneumonia and bone infection; empirical cover in septic shock with MRSA risk or in prosthetic device infection; ampicillin-resistant enterococcal infection; beta-lactam allergy.
• Not used for MSSA when a beta-lactam can be given, since outcomes are worse. Stop empirical vancomycin at 48 hours if MRSA is not isolated and risk is low.
• Meningitis from highly penicillin-resistant pneumococci: vancomycin with ceftriaxone.

Contraindications. Hypersensitivity to glycopeptides.

Serious effects.

• Nephrotoxicity, dose and exposure-related, with higher risk with piperacillin-tazobactam, loop diuretics, aminoglycosides and critical illness.
• Vancomycin infusion reaction (flushing and hypotension from histamine release; slow the infusion and give an antihistamine).
• Ototoxicity (rare), neutropenia and thrombocytopenia after 2 weeks, DRESS, linear IgA bullous dermatosis, phlebitis.

Monitoring.

• Baseline creatinine; renal function at least every 2 to 3 days (daily in unstable patients).
• Vancomycin level or AUC after the fourth dose, and after any change in renal function.
• Full blood count weekly.
• Teicoplanin trough on day 4 to 5 and again weekly.

Special groups.

• Pregnancy: use when indicated, with levels; breastfeeding is compatible.
• Renal impairment: dosing interval is extended and adjusted to levels; haemodialysis patients receive a load of 20 to 25 mg/kg and re-dosing after dialysis adjusted to levels.
• Obesity: loading dose uses actual body weight with a cap; maintenance uses actual weight with level-based adjustment.
• Older adults: reduced clearance and higher renal and ototoxicity risk.
• Region: MRSA prevalence varies across East African hospitals; local data should decide empirical use.

Referral and escalation. Persistent MRSA bacteraemia over 72 hours, elevated MIC, endocarditis, CNS or implant infection: seek infectious diseases advice and consider alternatives (daptomycin, linezolid, ceftaroline).