| Indication |
For the treatment of serious or severe infections caused by
susceptible strains of methicillin-resistant (beta-lactam-resistant)
staphylococci. |
| Pharmacodynamics |
Vancomycin is a branched tricyclic glycosylated nonribosomal peptide produced by the fermentation of the Actinobacteria species Amycolatopsis orientalis (formerly Nocardia orientalis).
It is often reserved as the "drug of last resort", used only after
treatment with other antibiotics had failed. Vancomycin has been shown
to be active against most strains of the following microorganisms, both
in vitro and in clinical infections: Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Actinomyces species, and Lactobacillus
species. The combination of vancomycin and an aminoglycoside acts
synergistically in vitro against many strains of Staphylococcus aureus,
Streptococcus bovis, enterococci, and the viridans group streptococci. |
| Mechanism of action |
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. |
| Absorption |
Poorly absorbed from gastrointestinal tract, however systemic
absorption (up to 60%) may occur following intraperitoneal
administration. |
| Volume of distribution |
Not Available |
| Protein binding |
Approximately 55% serum protein bound. |
| Metabolism |
Not Available |
| Route of elimination |
In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. |
| Half life |
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. |
| Clearance |
|
| Toxicity |
The oral LD50 in mice is 5000 mg/kg. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice. |
