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INTRODUCTION

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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 who are allergic to penicillins.

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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.

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THERAPEUTIC AND TOXIC CONCENTRATIONS

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Vancomycin is administered as a short-term (1 hour) intermittent intravenous infusion for doses up to 1500 mg or as a 1.5- to 2-hour intermittent intravenous infusion for larger doses (>1500 mg). 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- to 2-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 ½- to 1-hour waiting period is allowed for distribution to finish before maximum or “peak” concentrations are measured. Because vancomycin exhibits time-dependent killing, microbiologic 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 Because vancomycin does not enter the central nervous system in appreciable amounts when given intravenously,3 steady-state peak concentrations of 50-60 μg/mL, steady-state trough concentrations of 15-20 μg/mL, or direct administration into the cerebral spinal fluid may be necessary.6,7, and 8

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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 ½- to 1-hour waiting time for vancomycin distribution to tissues is allowed before peak concentrations are measured.

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Trough concentrations (predose or minimum concentrations usually obtained within 30 minutes of the next dose) are usually related to therapeutic outcome for vancomycin because the antibiotic follows time-dependent bacterial killing.1 Optimal bactericidal effects are found at concentrations three to five times the organism’s MIC.1,2 Because the ...

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