ASHP Therapeutic Position Statements 685 Therapeutic Monitoring of Vancomycin in Adult Patients : A Consensus Review of the American Society of HealthSystem Pharmacists

Vancomycin is a glycopeptide antibiotic that has been in clinical use for nearly 50 years as a penicillin alternative to treat penicillinase-producing strains of Staphylococcus aureus. It is one of the most widely used antibiotics in the United States for the treatment of serious gram-positive infections involving methicillin-resistant S. aureus (MRSA). Early use of vancomycin was associated with a number of adverse effects, including infusion-related toxicities, nephrotoxicity, and possible ototoxicity. Upon further investigation, it appears that the impurities in early formulations of vancomycin caused many of these adverse events. Its overall use was curtailed significantly with the development of semisynthetic penicillins (e.g., methicillin, oxacillin, nafcillin) that were considered less toxic. However, the steady rise in the number of MRSA infections since the early 1980s has once again brought vancomycin into the forefront as the primary treatment for infections caused by this organism. Over the years, vancomycin has been one of the most studied antibiotics. Extensive pharmacokinetic studies in a variety of patient populations and the availability of commercial drug assays have allowed clinicians to target serum vancomycin concentrations precisely in a relatively narrow range. This approach has been advocated to lessen the potential for nephrotoxicity and ototoxicity and to achieve therapeutic concentrations. However, it should be noted that the practice of routine monitoring and adjusting of serum vancomycin drug concentrations has been the subject of intense debate for many years. The controversy has resulted from conflicting evidence regarding the use of serum vancomycin concentrations to predict and prevent drug-induced toxicity and as a measure of effectiveness in treating infections. Further, data derived from more recent studies appear to suggest that vancomycin has little potential for nephrotoxicity or ototoxicity when used at conventional dosages (e.g., 1 g every 12 hours [15 mg/kg every 12 hours]), unless it is used concomitantly with known nephrotoxic drugs or at very high dosages. This consensus review evaluates the scientific data and controversies associated with serum vancomycin monitoring and provides recommendations based on the available evidence. This is a consensus statement of the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP). Consensus committee members were assigned key topics regarding vancomycin that contribute to current knowledge about patient monitoring. A draft document addressing these areas that included specific recommendations was reviewed by all committee members. After peer review by members of ASHP, IDSA, and SIDP, the committee met to review the submitted comments and recommendations. After careful discussion and consideration of these suggestions, the document was revised and circulated among the committee and supporting organizations for final comment. This consensus review represents the opinion of the majority of committee members. A search of PubMed was conducted using the following search terms: vancomycin pharmacokinetics, pharmacodynamics, efficacy, resistance, and toxicity. All relevant and available peer-reviewed studies in the English language published between 1958 and 2008 were considered. Studies were rated by their quality of evidence, and the subsequent recommendations were graded using the classification schemata of the Canadian Medical Association (Table 1). Recommendations of the expert panel are presented in Table 2. Potential limitations of this review include the facts that few prospective or randomized trials of vancomycin monitoring were available and that most of the published literature regarding vancomycin monitoring described observational studies in patients with S. aureus infection. Vancomycin monitoring in pediatric patients is beyond the scope of this review.