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 1–2 hours, by reducing the dose, or by pretreating with a histamine antagonist such as hydroxyzine.