For the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci.
The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
The oral LD<sub>50</sub> in mice is 5000 mg/kg. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice.
Poorly absorbed from gastrointestinal tract, however systemic absorption (up to 60%) may occur following intraperitoneal administration.
Half-life in normal renal patients is approximately 6 hours (range 4 to 11 hours). In anephric patients, the average half-life of elimination is 7.5 days.
In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration.
* 0.06 L/kg/h