"How it works" series: Vancomycin

(Click to enlarge)

Vancomycin was the first antibiotic developed of the glycopeptide class.  It is termed "glyco-" because it has two saccharides and "peptide" because it has seven peptides, making a structure larger than almost all other antibiotics.  The main mechanism of action is inhibition of cell wall synthesis.  Under normal conditions in bacteria, as the cell wall is being formed,
the pentapeptides (five dots seen in the image) usually have cross-linking or cross-bridges formed (the yellow pentaglycine chains), strengthening the cell wall.  When vancomycin crosses the cell membrane, it binds to the last peptide, D-alanyl-D-alanine (red dot in the picture), and forms a stable complex, preventing subsequent cross-bridging, and thereby interrupting cell wall synthesis.  Vancomycin does not even cross into the cell's cytoplasm.

Resistance to vancomycin occurs differently in differnt organisms.  In enterococci, resistance occurs by forming a peptidoglycan variant (a different five dots or different end terminal other than D-alanyl-D-alanine) that vancomycin has decreased affinity for.  But in S. aureus, resistance is likely due to thickened cell walls and increased amounts of D-alanyl-D-alanine, which traps vancomycin.

Other notable features:

• For Gram-positive organisms including:
• Staphylococcus (including MRSA), streptococcus, Bacillus, Corynebacterium
• Coagulase-negative staphylococci
• Most enterococcus faecalis, Listeria
• Some enterococcus faecium
• Anaerobes
• Peptostreptococcus, Clostridium (including difficile)
• Not for almost any Gram-negative organisms
• Concentration-independent bactericidal activity (once a certain concentration acheived)
• 24-hour AUC/MIC ratio is best predictor of clinical efficacy (at least 400)
• Check serum trough concentrations as a surrogate for this parameter because of accuracy and practicality
• Excreted unchanged by the kidneys through glomerular filtration so adjust with decreased creatinine clearance
• To learn about vancomycin dosing in hemodialysis, see the discussion here.
• Give IV for systemic infections (poor oral absorption)

References:
Murray BE, Nannini, EC.  Chapter 31: Glycopeptides (Vancomycin and Teicoplanin), Streptogramins, (Quinupristin-Dalfopristin), and Lipopeptides (Daptomycin).  In: Mandell GL, Bennett JE, Dolin R, eds.  Principles and practice of infectious diseases. 7th ed. Philadelphia, PA: Elsevier; 2010:449-67.
Rybak M, Lomaestro B, Rotschafer JC, et al.  Therapeutic monitoring of vancomycin in adult patients: A concensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.  Am J Health-Syst Pharm  2009;66:82-98.

image adapted from Mcstrother