Important indications for parenteral vancomycin are bloodstream infections and endocarditis caused by methicillin-resistant staphylococci. However, vancomycin is not as effective as an antistaphylococcal penicillin for treatment of serious infections such as endocarditis caused by methicillin-susceptible strains. Vancomycin in combination with gentamicin is an alternative regimen for treatment of enterococcal endocarditis in a patient with serious penicillin allergy. Vancomycin (in combination with cefotaxime, ceftriaxone, or rifampin) is also recommended for treatment of meningitis suspected or known to be caused by a penicillin-resistant strain of pneumococcus. The recommended dosage in a patient with normal renal function is 30–60 mg/kg/d in two or three divided doses. The traditional dosing regimen in adults with normal renal function is 1 g every 12 hours (~30 mg/kg/d); however, this dose will not typically achieve the trough concentrations (15–20 mcg/mL) recommended for serious infections. For serious infections (see below), a starting dose of 45–60 mg/kg/d should be given with titration of the dose to achieve trough levels of 15–20 mcg/mL. The dosage in children is 40 mg/kg/d in three or four divided doses. Clearance of vancomycin is directly proportional to creatinine clearance, and the dosage is reduced accordingly in patients with renal insufficiency. For patients receiving hemodialysis, a common dosing regimen is a 1-g loading dose followed by 500 mg after each dialysis session. Patients receiving a prolonged course of therapy should have serum trough concentrations checked. For S aureus infections, recommended trough concentrations are 10–15 mcg/mL for mild to moderate infections and 15–20 mcg/mL for more serious infections such as endocarditis, meningitis, and necrotizing pneumonia.
Oral vancomycin, 0.125–0.5 g every 6 hours, is used to treat colitis caused by C difficile. Because of the emergence of vancomycin-resistant enterococci and the potential selective pressure of oral vancomycin for these resistant organisms, metronidazole had been preferred as initial therapy. However, use of oral vancomycin does not appear to be a significant risk factor for acquisition of vancomycin-resistant enterococci. Additionally, recent clinical data suggest that vancomycin is associated with higher initial response rates than metronidazole, particularly for moderate to severe cases of C difficile colitis. Therefore, oral vancomycin may be used as a first-line treatment, especially for severe cases.
Adverse reactions with parenteral administration of vancomycin are encountered fairly frequently. Most reactions are relatively minor and reversible. Vancomycin is irritating to tissue, resulting in phlebitis at the site of injection. Chills and fever may occur. Ototoxicity is rare but nephrotoxicity is still encountered regularly with current preparations, especially with high trough levels.
Administration with another ototoxic or nephrotoxic drug, such as an aminoglycoside, increases the risk of these toxicities. Ototoxicity can be minimized by maintaining peak serum concentrations below 60 mcg/mL. Among the more common reactions is the so-called “red man” syndrome. This infusion-related flushing is caused by release of histamine. It can be largely prevented by prolonging the infusion period to 1–2 hours (preferred) or pretreatment with an antihistamine such as diphenhydramine.