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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.
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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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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
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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 ...