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Vancomycin is a glycopeptide antibiotic used to treat severe gram-positive infections due to organisms that are resistant to other antibiotics such as methicillin-resistant staphylococci and ampicillin-resistant enterococci. It is also used to treat infections caused by other sensitive gram-positive organisms in patients that are allergic to penicillins.

Vancomycin is bactericidal and exhibits time-dependent or concentration-independent bacterial killing.1 Antibiotics with time-dependent killing characteristically kill bacteria most effectively when drug concentrations are a multiple (usually three to five times) of the minimum inhibitory concentration (MIC) for the bacteria.1,2 The mechanism of action for vancomycin is inhibition of cell wall synthesis in susceptible bacteria by binding to the d-alanyl-d-alanine terminal end of cell wall precursor units.3 Many strains of enterococcus have high MIC values for vancomycin, and for these bacteria vancomycin may only demonstrate bacteriostatic properties.

Vancomycin is administered as a short-term (1-hour) intravenous infusion. Infusion rate related side effects have been noted when shorter infusion times (~30 minutes or less) have been used. Urticarial or erythematous reactions, intense flushing (known as the “red-man” or “red-neck” syndrome), tachycardia, and hypotension have all been reported and can be largely avoided with the longer infusion time. Even with a 1-hour infusion time, vancomycin serum concentrations exhibit a distribution phase so that drug in the blood and in the tissues are not yet in equilibrium (Figure 5-1). Because of this, a 1/2–1 hour waiting period is allowed for distribution to finish before maximum or “peak” concentrations are measured. Since vancomycin exhibits time-dependent killing, microbiolgic or clinical cure rates are not closely associated with peak serum concentrations. However, ototoxicity has been reported when vancomycin serum concentrations exceed 80 μg/mL,4,5 so the therapeutic range for steady-state peak concentrations is usually considered to be 20–40 μg/mL. Because vancomycin does not enter the central nervous system in appreciable amounts when given intravenously,3 steady-state peak concentrations of 40–60 μg/mL or direct administration into the cerebral spinal fluid may be necessary.6,7

Figure 5-1

Concentration/time plot for vancomycin 1000 mg given as a 1-hour infusion (circles with dashed line). When given as a 1-hour infusion, end of infusion concentrations are higher because the serum and tissues are not in equilibrium. A 1/2- to 1-hour waiting time for vancomycin distribution to tissues is allowed before peak concentrations are measured.

Vancomycin-associated ototoxicity is usually first noted by the appearance of tinnitus, dizziness, or high-frequency hearing loss (>4000 Hz).4,7,8 Because the hearing loss is initially at high-frequencies, the auditory deficit can be challenging to detect unless audiometry is conducted at baseline before drug is administered and during vancomycin treatment. Since audiometry is difficult to conduct in seriously ill patients, it is rarely done in patients receiving ototoxic drugs so ...

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