Introduction
Vancomycin is a glycopeptide antibiotic first isolated from Amycolatopsis orientalis (formerly Streptomyces orientalis) in the 1950s. It remains a cornerstone in the treatment of serious Gram-positive bacterial infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug-resistant organisms. Vancomycin's importance has grown significantly with the global rise of antimicrobial resistance.
Mechanism of Action
Vancomycin exerts its bactericidal effect by inhibiting cell wall synthesis in Gram-positive bacteria. It binds with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units, preventing cross-linking of peptidoglycan chains by transpeptidase enzymes. This disruption of cell wall synthesis leads to osmotic instability and ultimately bacterial cell lysis.
Indications
FDA-approved indications include:
- Serious or severe infections caused by susceptible strains of methicillin-resistant staphylococci
- Empiric therapy for presumed MRSA infections in critically ill patients
- Treatment of antibiotic-associated colitis caused by Clostridium difficile (oral formulation only)
- Treatment of staphylococcal endocarditis when penicillins are contraindicated
Off-label uses include:
- Surgical prophylaxis in patients with β-lactam allergy
- Treatment of device-related infections
- Central nervous system infections caused by susceptible Gram-positive organisms
Dosage and Administration
Intravenous Administration:- Adults: 15-20 mg/kg (based on actual body weight) every 8-12 hours
- Target trough concentrations: 15-20 μg/mL for serious infections
- Loading dose: 25-30 mg/kg may be considered for critically ill patients
- C. difficile infection: 125 mg orally four times daily for 10 days
- Dosing adjustment required in renal impairment
- Renal impairment: Dose adjustment based on creatinine clearance
- Obesity: Use actual body weight for dosing
- Pediatrics: 40-60 mg/kg/day divided every 6-8 hours
- Geriatrics: Consider reduced dosing due to age-related renal changes
Pharmacokinetics
Absorption: Poor oral bioavailability (<10%); requires IV administration for systemic infections Distribution: Widely distributed in body tissues and fluids; crosses inflamed meninges Volume of Distribution: 0.4-1.0 L/kg Protein Binding: Approximately 55% Metabolism: Minimal hepatic metabolism Elimination: Primarily renal excretion (80-90% unchanged in urine) Half-life: 4-6 hours in patients with normal renal functionContraindications
- Hypersensitivity to vancomycin or other glycopeptide antibiotics
- Known history of vancomycin-induced neutropenia
- Concurrent administration with other ototoxic or nephrotoxic drugs when avoidance is possible
Warnings and Precautions
Black Box Warning:- Rapid IV infusion may cause hypotension, flushing, erythema, urticaria, and pruritus ("Red Man Syndrome")
- Ototoxicity - permanent hearing loss may occur
- Nephrotoxicity - renal failure may occur
- Vancomycin-resistant enterococci (VRE) and vancomycin-intermediate S. aureus (VISA) have emerged
- Requires therapeutic drug monitoring to optimize efficacy and minimize toxicity
- Use with caution in patients with renal impairment or pre-existing hearing loss
Drug Interactions
- Aminoglycosides: Increased risk of nephrotoxicity and ototoxicity
- Loop diuretics: Enhanced ototoxicity potential
- Anesthetic agents: Increased risk of hypotension with rapid infusion
- Colistin: Additive nephrotoxicity risk
- IV contrast media: Potential additive nephrotoxicity
Adverse Effects
Common (≥1%):- Infusion-related reactions ("Red Man Syndrome")
- Nephrotoxicity (elevated serum creatinine)
- Ototoxicity (tinnitus, hearing loss)
- Phlebitis at injection site
- Neutropenia (usually reversible)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acute kidney injury requiring dialysis
- Permanent hearing loss
Monitoring Parameters
Essential Monitoring:- Serum trough concentrations (drawn within 30 minutes before next dose)
- Serum creatinine daily
- Complete blood count with differential 2-3 times weekly
- Audiometric testing baseline and periodically during prolonged therapy
- Signs and symptoms of infusion reactions
- Uncomplicated infections: 10-15 μg/mL
- Serious infections: 15-20 μg/mL
- Complicated infections: 15-20 μg/mL
- Avoid trough concentrations >20 μg/mL due to increased nephrotoxicity risk
Patient Education
- Report any hearing changes, ringing in ears, or dizziness immediately
- Inform all healthcare providers of vancomycin use
- Complete the full course of therapy unless instructed otherwise
- Maintain adequate hydration unless contraindicated
- Be aware of potential infusion reactions and report any flushing, itching, or rash during infusion
- Regular blood tests are necessary to monitor drug levels and kidney function
References
1. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864.
2. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55.
3. FDA Prescribing Information: Vancomycin Hydrochloride Injection. 2021.
4. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2017.
5. Lexicomp Online. Vancomycin: Drug Information. Wolters Kluwer Clinical Drug Information, Inc.; 2023.
Note: This monograph provides general information and should not replace clinical judgment. Always consult current guidelines and institutional protocols for specific patient care decisions.