Vancomycin is bactericidal for most gram-positive organisms, particularly
staphylococci and streptococci; it is, however, bacteriostatic for most enterococci.
While active against staphylococci, vancomycin kills more slowly
when compared with nafcillin. Although vancomycin has retained activity
against staphylococci and streptococci, vancomycin-resistant strains
of enterococci (particularly E faecium) have emerged. S
aureus both intermediately sensitive and highly vancomycin-resistant has been observed in patients receiving long-term vancomycin therapy. Vancomycin is not absorbed from the gastrointestinal tract and thus useful orally only for the treatment of antibiotic-associated enterocolitis. For systemic effect, the drug must be administered intravenously (30 mg/kg/d in two or three divided doses). Vancomycin is excreted mainly via the kidneys. In end-stage kidney disease, the half-life may extend to 8 days. Vancomycin is cleared via high-flux hemodialysis and continuous arteriovenous hemofiltration (CAVH), resulting in the need for increased dosing. In patients with impaired kidney function, the dosing interval is determined by measuring trough serum levels. When trough serum levels decline to 10–15 mcg/mL, repeat dosing is required. Recent guidelines have suggested more aggressive dosing with associated troughs of > 15 mcg/mL in the treatment of methicillin-resistant S aureus ventilator-associated pneumonia. However, the association of attainment of these elevated trough levels and efficacy has not been proven. Large doses ( 4 g daily) have been associated with mild reversible nephrotoxicity. Vancomycin efficacy is closely correlated with pharmacokinetics/pharmacodynamics. Specifically, area-under-the-curve divided by the minimum inhibitory concentration (MIC) of > 400 has been associated with favorable outcomes in serious infection due to S aureus. Considering this relationship, the MIC is critical toward the decision to use vancomycin; in those instances in which the MIC is 2 mcg/mL (or 1.5 mcg/mL by E-test), alternatives to vancomycin should be used. These include daptomycin, linezolid, televancin, and other agents, depending on the site of infection.
Indications for parenteral vancomycin include the following:
(1) Severe staphylococcal infections in penicillin-allergic patients;
for methicillin-resistant S aureus and S epidermidis infections
and for serious infections (pneumonia, meningitis) due to resistant S pneumoniae. (2) Severe enterococcal infections
in the penicillin-allergic patient or if the enterococcus is penicillin-resistant.
(3) Other gram-positive infections in penicillin-allergic patients,
eg, viridans streptococcal endocarditis. (4) Surgical prophylaxis
in penicillin-allergic patients. (5) For gram-positive infections
due to organisms that are multidrug-resistant, ie, Corynebacterium
jeikeium. (6) Endocarditis prophylaxis in the penicillin-allergic
patient. In antibiotic-associated enterocolitis, vancomycin, 0.125
g, is given orally four times daily. Oral vancomycin is preferred
over oral metronidazole in the treatment of severe C difficile disease.
Thrombophlebitis sometimes follows intravenous injection. The
drug is infrequently ototoxic when given concomitantly with aminoglycosides
or high-dose intravenous erythromycins; it is potentially nephrotoxic
when administered with aminoglycosides. Some studies suggest larger
vancomycin doses or elevated trough levels or both to be associated with an increased incidence of mild
nephrotoxicity. Rapid infusion or high doses (1 g or more) may induce
diffuse hyperemia ("red man syndrome") and can
be avoided by extending infusions over 12 hours, by reducing
the dose, or by pretreating with a histamine antagonist such as
|Liu C et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb;52(3):e18–55.
|Rybak MJ et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 2009 Aug 1;49(3):325–7.
|van Hal SJ et al. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012 Mar;54(6):755–71. [PMID: 22302374]|