Accuracy of measured vancomycin serum concentrations in patients with end-stage renal disease

OBJECTIVE: To review information related to the accuracy of vancomycin serum drug concentrations in patients with end-stage renal disease, focusing on available assays and mechanisms of cross-reactivity. DATA SOURCES: Primary and review articles identified from a MEDLINE search (January 1980-June 1999) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All articles identified were evaluated, and all relevant information was included in this review. DATA SYNTHESIS: Falsely elevated vancomycin serum concentrations may occur in patients with renal dysfunction. The underlying mechanism is due to the formation and accumulation of a pseudo-metabolite, the vancomycin crystalline degradation product (CDP). Vancomycin is converted to CDP when exposed to heat, including normal body temperature. Because the molecular structures of CDP and vancomycin are similar, both molecules are detected by polyclonal immunoassay systems used in clinical laboratories. This cross-reactivity leads to falsely elevated serum vancomycin concentrations in excess of 50-70%. Such large assay inaccuracies may result in improper dosage adjustments and therapeutic failures. A monoclonal immunoassay system has been developed that does not significantly cross-react with CDP. CONCLUSIONS: To appropriately interpret laboratory results, it is essential for clinicians to be aware of the vancomycin-CDP cross-reactivity problem and to be familiar with the specific assay used to measure vancomycin concentrations in patients with renal dysfunction.