Vancomycin

• MRSA Infections
• C. difficile Colitis
• Endocarditis
• Bone and Joint Infections

Vancomycin is a glycopeptide antibiotic used to treat serious gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It remains one of the most important antibiotics for treating resistant gram-positive infections.

Mechanism of Action

Vancomycin inhibits bacterial cell wall synthesis:

• D-Ala-D-Ala binding: Binds to the D-alanyl-D-alanine terminus of cell wall precursor units
• Blocks transglycosylation: Prevents incorporation of N-acetylmuramic acid and N-acetylglucosamine into peptidoglycan
• Prevents transpeptidation: Blocks cross-linking of peptidoglycan strands
• Cell wall weakening: Results in cell lysis due to osmotic stress
• Bactericidal: Time-dependent killing against most gram-positive bacteria

Vancomycin's large molecular size prevents penetration through gram-negative outer membrane.

Available Formulations

• IV injection: 500 mg, 750 mg, 1 g, 1.5 g, 5 g, 10 g vials
• Oral capsules: 125 mg, 250 mg
• Oral solution: 25 mg/mL, 50 mg/mL

Oral formulations are NOT absorbed systemically and are used only for C. difficile colitis.

Medical Uses

FDA-Approved Indications:

• Serious gram-positive infections (IV): Endocarditis, bone and joint infections, bloodstream infections, pneumonia, skin and soft tissue infections
• Clostridioides difficile-associated diarrhea (oral only)
• Staphylococcal enterocolitis (oral)

IV vancomycin is often reserved for MRSA or penicillin-allergic patients with serious gram-positive infections.

Dosing Guidelines

Serious Infections (IV):

• Loading dose: 25-30 mg/kg (actual body weight)
• Maintenance: 15-20 mg/kg every 8-12 hours
• Target trough: 15-20 mcg/mL for serious infections
• AUC/MIC-guided dosing: AUC 400-600 mg*hr/L preferred

C. difficile Infection (Oral):

• Initial episode: 125 mg four times daily for 10-14 days
• Severe or fulminant: 500 mg four times daily
• Recurrence: Various regimens including pulsed/tapered dosing

Renal Impairment: Significant dose adjustments required; extend interval based on CrCl.

Important Safety Information

Contraindications:

• Known hypersensitivity to vancomycin

Warnings and Precautions:

• Nephrotoxicity: Risk increases with concomitant nephrotoxins, prolonged therapy, high doses
• Ototoxicity: Rare but may occur; usually reversible
• Infusion-related reactions: "Red man syndrome" from rapid infusion; slow infusion rate
• Drug-induced immune thrombocytopenia: Has been reported
• DRESS syndrome: Severe cutaneous reactions possible
• Superinfection: May promote fungal overgrowth

Drug Interactions

• Nephrotoxic drugs (aminoglycosides, amphotericin B, NSAIDs): Increased nephrotoxicity risk
• Ototoxic drugs: May increase ototoxicity risk
• Anesthetic agents: May increase risk of erythema and histamine-like flushing
• Neuromuscular blocking agents: May potentiate effects

Special Populations

• Hepatic Impairment: No adjustment needed (not hepatically metabolized)
• Renal Impairment: Significant dose adjustments required; consider pharmacist consultation
• Elderly: More susceptible to toxicity; dose based on renal function
• Pregnancy: Category B (oral); Category C (IV); use when benefit outweighs risk
• Pediatric: Weight-based dosing; therapeutic drug monitoring recommended
• Obese patients: Use actual body weight for loading; consider monitoring