Overdosage
Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance. The median lethal intravenous dose is 319 mg/kg in rates and 400 mg/kg in mice. In managing overdose, consider the possibility of multiple drug overdose, interaction among drugs, and unusual drug kinetics in your patient.
Clinical Pharmacology
Vancomycin is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Intramuscular injection is painful. In subjects with normal kidney function, multiple intravenous drug of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations or approximately 63 mg/L immediately after the completion of infusion, mean plasma concentrations of approximately 23 mg/L 2 hours after infusion, and mean plasma concentrations of approximately 9 mg/L 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mg/L at the completion of infusion, mean plasma concentrations of about 19 mg/L 2 hours after infusion, and mean plasma concentrations of about 10 mg/L 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose. The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg?h, and mean renal clearance is about 0.048 L/kg/h. Renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg.
There is no apparent metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mg/L are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. Although vancomycin is not effectively removed by either hemodialysis or peritoneal dialysis, there have been reports of increased vancomycin clearance with hemoperfusion and hemofiltration.
Total systemic and renal clearance of vancomycin may be reduced in the elderly. Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mg/L. After IV administration of vancomycin hydrochloride, inhibitory concentrations are present in pleural, pericardia, ascetic, and synovial fuids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin hydrochloride does not readily diffuse across normal meninges into the spinal fluid; but when the meninges are inflamed, penetration into the spinal fluid occurs.
Microbiology
The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is active against staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogenous methicillin-resistant strains); streptococci, including Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, the viridans groups, Streptococcus bovis, and enterococci (e.g. Enterococcus faecalis [formely Streptococcus faecalis]); Clostridium difficile (eg. Toxigenic strains implicated in pseudomembranous enterocolitis); and diphtheroids. Other organisms that are susceptible to vancomycin in vitro include Listeria monocytogenes, Lactobacillus species, Actinomyces species, Clostridium species, and Bacillus species.
Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. In vitro resistance to vancomycin has been reported among some enterococcal and staphylococcal isolates.
Synergy
The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of S. aureus, nonenterococcal group D streptococci, enterococci, and Streptococcusspecies (viridans group).
Disk Susceptibility Tests
The standardized disk method described by the National Committee for Clinical Laboratory Standards has been recommended to test susceptibility to vancomycin. Results of standard susceptibility tests with a 30 microgram vancomycin hydrochloride disk should be interpreted according to the following criteria: Susceptible organisms produce zones greater than or equal to 12 mm, indicating that the test organism is likely to respond to therapy. Organisms that produces zones of 10 or 11 mm are considered to be of intermediate susceptibility. Organisms in this category are likely to respond if the infection is confined to tissues or fluids in which high antibiotic concentrations are attained. Resistant organisms produce zones of 9 mm or less, indicating that other therapy should be selected.
Using a standardized dilution method, a bacterial isolate maybe considered susceptible if the MIC value for vancomycin is 4 mg/L or less. Organisms are considered resistant to vancomycin if the MIC is greater than or equal to 16 mg/L. Organisms having an MIC value of less than 16 mg/L but greater than 4 mg/L are considered to be of intermediate susceptibility.
Standardized procedures require the use of laboratory control organisms. The 30 micrograms vancomycin disk should give diameters between 15 and 19 mm for S. aureus ATCC 25923. As with the standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard vancomycin powder should give MIC values in the range of 0.5 mg/L to 2.0 mg/L for S. aureus ATCC 29213. For E. faecalis ATCC 29212, the MIC range should be 1.0 to 4.0 mg/L