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PHARMACOLOGY NOTES
Recommendations for monitoring serum vancomycin
concentrations
CHRISTOPHER W. JAMES, PHARMD, AND CHERYLE GURK-TURNER, RPH
V
ancomycin is a glycopeptide antibiotic that has been
used for the treatment of infections due to gram-positive
microorganisms since 1956 (1). Shortly thereafter,
Geraci et al described 2 cases of irreversible ototoxicity secondary to vancomycin therapy, with serum concentrations ranging
from 80 to 100 mg/L (2). Based on this, the authors recommended
therapeutic drug monitoring of vancomycin to reduce the risk of
ototoxicity. The practice of routine therapeutic drug monitoring
originated when the guidelines for monitoring peak and trough
concentrations of aminoglycosides were applied to vancomycin
therapy, based on similarities in pharmacokinetic and toxicity
profiles (e.g., nephrotoxicity and ototoxicity) (3–5). However, the
pharmacodynamics of vancomycin, which exhibits concentration-independent activity, are quite different from those of the
aminoglycosides, which display concentration-dependent killing
(5, 6). It is interesting to note that the manufacturer makes no
recommendations regarding therapeutic drug monitoring (7).
Therefore, the need for therapeutic drug monitoring in patients
receiving vancomycin is controversial. This article examines the
available evidence on the efficacy and toxicity of different concentrations of vancomycin and presents guidelines for therapeutic drug monitoring in patients receiving vancomycin therapy.
EFFICACY
Since vancomycin exhibits time-dependent killing of susceptible bacteria, the concentration of the drug must be maintained
above the minimum inhibitory concentration (MIC) for the
majority of the dosing interval (4). Researchers recommend
keeping the peak value 5 to 8 times the MIC and the trough value
1 to 2 times the MIC (MIC for most bacteria is <5 µg/mL) (6,
8). Vancomycin regimens that are based on empiric pharmacokinetics (using a patient’s age, weight, and renal function) or
adjusted based on serum levels have been shown to be equally
effective in treating gram-positive infections (9). Zimmerman et
al studied 273 patients receiving vancomycin and found that
patients whose trough concentrations were ≥10 mg/L were more
likely to become afebrile and have a normal white blood cell
count within 72 hours (10).
TOXICITY
Serum drug monitoring of vancomycin therapy has traditionally been recommended to avoid the nephrotoxicity and ototoxicity documented in case reports (11). Confounding factors in
these case reports include preexisting renal impairment and conBUMC PROCEEDINGS 2001;14:189–190
comitant therapy with other nephrotoxic or ototoxic agents,
including aminoglycosides, amphotericin, and furosemide (12).
Also complicating these early reports regarding nephrotoxicity
and ototoxicity were the impurities contained in the older preparations of vancomycin, once referred to as “Mississippi mud.”
These impurities may have been responsible for the toxicity (12,
13). The manufacturing process improved in the mid 1970s, resulting in fewer impurities and a decreased incidence of ototoxicity and infusion-related reactions (1).
Ototoxicity secondary to vancomycin is manifested by vestibular damage and/or cochlear damage, which leads to sensory
hearing loss and tinnitus (1). In 13 reports of vancomycin therapy
leading to reversible ototoxicity, no confounding factors (concomitant medications or disease states) were present (9). Vancomycin concentrations in these patients ranged from 17 to 62
mg/L, with the vast majority occurring in the accepted therapeutic
range (9). Reversible ototoxicity is generally associated with concentrations >40 mg/L. Irreversible damage is a rare complication
of vancomycin therapy and is usually encountered in patients with
concentrations >80 mg/L and preexisting renal impairment (14).
The generally accepted incidence of nephrotoxicity secondary to vancomycin monotherapy is <5% but increases to 43% in
patients receiving concomitant nephrotoxic medications (aminoglycosides, amphotericin) (1, 9, 14). Nephrotoxicity is generally reversible and is believed to result from the accumulation
of the drug in renal cells (1). In reported cases of vancomycininduced nephrotoxicity, concentrations were generally higher
than the accepted therapeutic range. However, given the drug’s
dependence on renal elimination, vancomycin concentrations
would be expected to be elevated in patients with renal dysfunction (15). Zimmerman et al found that in patients receiving
vancomycin alone, nephrotoxicity did not occur until the trough
concentrations exceeded 20 mg/L (10).
OTHER CONSIDERATIONS
Significant costs are associated with vancomycin therapeutic drug monitoring. In addition to the cost of the assay itself,
the cost of monitoring includes the time and effort of nurses,
From the Department of Pharmacy Services, Baylor University Medical Center,
Dallas, Texas.
Corresponding author: Cheryle Gurk-Turner, RPh, Department of Pharmacy Services, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, Texas 75246
(e-mail: [email protected]).
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pharmacists, laboratory personnel, and physicians (9). The cost
for a vancomycin serum level at our institution is $97.50. Phlebotomy associated with monitoring vancomycin levels also contributes to increased morbidity from venipuncture and lowered
hemoglobin from blood loss (15).
DISCUSSION
For vancomycin therapy to be optimal, adequate trough concentrations must be maintained and elevated peak concentrations
avoided. It can generally be assumed that trough concentrations
maintained below 15 mg/L would not provide peak concentrations that exceed 40 mg/L, except in patients with smaller volumes of distribution (13). Therefore, in most instances, optimal
vancomycin therapy can be assured with trough concentrations
alone. Some authors have recommended that vancomycin monitoring is not necessary at all, arguing that empiric dosing based
on nomograms almost always results in trough levels that exceed
the MIC of susceptible bacteria (9). However, therapeutic drug
monitoring is recommended in several instances: a) patients receiving concomitant aminoglycosides, b) anephric patients
receiving hemodialysis, especially high-flux dialysis such as continuous venovenous hemofiltration, c) patients receiving higherthan-normal doses of vancomycin (i.e., for meningitis), and d)
patients with rapidly changing renal function (12). Patients receiving hemodialysis should have vancomycin concentrations
drawn periodically (every 4 to 7 days) to ensure that therapeutic
levels are maintained. Therapeutic drug monitoring is also recommended in patients with high volumes of distribution, such as
burn patients and intravenous drug abusers (11).
Based on this information, the Pharmacy and Therapeutics
Committee at Baylor University Medical Center has adopted the
following guidelines:
• Routine monitoring of vancomycin peak and trough concentrations in all adult patients receiving vancomycin therapy
is not recommended unless therapy is longer than 5 days.
• Measurement of a single trough concentration at steady state
is recommended for the following patients:
– Patients receiving concomitant aminoglycosides
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– Patients receiving higher-than-normal doses of vancomycin (i.e., for meningitis)
– Patients with rapidly changing renal function
– Patients with altered volumes of distribution (burn patients, trauma patients, intravenous drug abusers)
– Patients in whom treatment is failing
• Anephric patients receiving hemodialysis should have vancomycin concentrations drawn periodically (approximately
every 4 to 7 days) to ensure that therapeutic levels are maintained.
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BAYLOR UNIVERSITY MEDICAL CENTER PROCEEDINGS
VOLUME 14, NUMBER 2