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 compared with nafcillin or cefazolin, and consequently, these beta-lactams are preferred in the treatment of serious infection due to methicillin-susceptible S aureus. Although vancomycin has retained activity against staphylococci and streptococci, vancomycin-resistant strains of enterococci (particularly E faecium) are common. 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 GI tract and thus useful orally only for the treatment of antibiotic-associated Clostridium enterocolitis. For systemic infection, vancomycin must be administered intravenously (30 mg/kg/day 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 renal replacement therapy, resulting in the need for maintenance dosing in such patients. 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, primarily in the treatment of severe infection. As an example, more aggressive dosing with associated troughs of greater than 15 mcg/mL has been recommended in the treatment of more serious methicillin-resistant S aureus infections. However, this practice has not resulted in increased efficacy. Large doses (4 g daily or more) and concomitant use of piperacillin-tazobactam have been associated with mild reversible nephrotoxicity. Vancomycin likely increases the risk of aminoglycoside-associated nephrotoxicity. Vancomycin efficacy correlates with pharmacokinetics/pharmacodynamics. Specifically, an area under the curve (AUC) divided by the minimum inhibitory concentration (MIC) of greater than 400 (AUC/MIC greater than 400) has been associated with favorable outcomes in serious infection due to S aureus. Attainment of this ratio appears to be particularly important during the first 2 days of therapy of methicillin-resistant S aureus bloodstream infections. Considering this relationship, the MIC is critical regarding the decision to use vancomycin; when the MIC is greater than or equal to 2 mcg/mL (or greater than or equal to 1.5 mcg/mL by E-test), alternatives to vancomycin (including daptomycin, linezolid, and other agents, depending on the site of infection) should be considered.
Indications for parenteral vancomycin include the following: (1) severe staphylococcal infections in patients with type 1 allergy to penicillins; (2) methicillin-resistant S aureus and methicillin-resistant S epidermidis infections; (3) serious infections (pneumonia, meningitis) due to resistant S pneumoniae; (4) severe enterococcal infections in the penicillin-allergic patient or ampicillin-resistant Enterococcus; (5) other gram-positive infections in penicillin-allergic patients, eg, viridans streptococcal endocarditis; (6) surgical prophylaxis in patients with severe beta-lactam allergy in clean surgical procedures; (7) for gram-positive infections due to organisms that are multidrug-resistant, ie, Corynebacterium jeikeium; and (8) endocarditis prophylaxis in the patient with severe penicillin allergy. In C difficile–associated disease, vancomycin, 125 mg, is given orally four times daily. Oral vancomycin is preferred over oral metronidazole in the treatment of C difficile disease. Oral doses in excess of 125 mg are not associated with improved outcomes in the treatment of this disease, although it is recommended in severe recurrent disease. The 2021 IDSA guidelines recommend fidaxomicin over vancomycin in the treatment of uncomplicated first time C difficile enterocolitis.
Thrombophlebitis sometimes follows intravenous injection. The medication is infrequently reversibly ototoxic when given concomitantly with aminoglycosides or high-dose intravenous erythromycins; it increases aminoglycoside-induced nephrotoxicity with coadministration. Concomitant administration of vancomycin with piperacillin-tazobactam increases the risk for nephrotoxicity; this association has not been observed when vancomycin is combined with other beta-lactams. Vancomycin doses of 4 g or greater daily and elevated trough levels are also associated with an increased incidence of mild nephrotoxicity. Rapid infusion or high doses (1 g or more) may induce diffuse hyperemia and hypotension 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.