Vancomycin
Vancomycin is a glycopeptide antibiotic from Amycolatopsis orientalis that inhibits cell wall synthesis in gram-positive bacteria, including MRSA.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C66H75Cl2N9O24 |
| Molecular Weight | 1449.25 g/mol |
| CAS Number | 1404-90-6 |
| IUPAC Name | Vancomycin hydrochloride |
| Peptide Class | Glycopeptide Antibiotic |
| Origin | Amycolatopsis orientalis |
Structure
Vancomycin is a tricyclic glycopeptide consisting of seven amino acids, including several unusual non-proteinogenic residues (beta-hydroxytyrosine, 4-hydroxyphenylglycine, and beta-hydroxychloroethylglycine). Two chlorinated aromatic rings and three fused macrocyclic rings create a rigid cup-shaped structure. A disaccharide (vancosamine-glucose) is attached to ring 4. The heptapeptide core is produced non-ribosomally by NRPS enzymes.
Mechanism of Action
Vancomycin binds with high affinity to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the peptidoglycan precursor lipid II, blocking both transglycosylation and transpeptidation steps of cell wall synthesis. This binding is stoichiometric and irreversible, making vancomycin bactericidal against most gram-positive organisms. Unlike beta-lactams, the target is the substrate rather than an enzyme.
Clinical Applications
Vancomycin is approved for:
- MRSA infections: Bacteremia, endocarditis, pneumonia, osteomyelitis
- Clostridioides difficile infection: Oral vancomycin for C. difficile colitis
- Prosthetic joint infections: As part of combination therapy
- Surgical prophylaxis: In patients with MRSA risk factors
Intravenous dosing requires therapeutic drug monitoring (trough 10-20 mcg/mL for serious infections). AUC/MIC ratio >400 is the preferred pharmacodynamic target.
Pharmacokinetics
- Half-life: 4-6 hours (normal renal function); extended in renal impairment
- Protein binding: 30-55%
- Metabolism: Not significantly metabolized
- Elimination: Primarily renal (80-90% unchanged)
- Dialysis: Not significantly removed by hemodialysis
Safety and Side Effects
Red man syndrome (histamine-mediated flushing and hypotension with rapid infusion), nephrotoxicity (especially with concurrent nephrotoxins or trough >20 mcg/mL), ototoxicity (rare with modern dosing), and thrombocytopenia (vancomycin-dependent antibodies). Infusion rate should not exceed 10 mg/min to prevent red man syndrome.
References
- Levine, D.P. (2006). Vancomycin: a history. Clinical Infectious Diseases, 42, S5-S12.
- Rybak, M., et al. (2009). Therapeutic monitoring of vancomycin in adult patients. American Journal of Health-System Pharmacy, 66, 82-98.
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