Vancomycin-induced neutropenia: is it dose- or duration-related?

OBJECTIVE

To systematically evaluate the literature to determine whether vancomycin-induced neutropenia is dose- or duration-related and provide clinicians with feasible treatment alternatives.

DATA SOURCES

A literature search of PubMed (1949-November 2010), MEDLINE (1950-November 2010), EMBASE (1980-November 2010), and International Pharmaceutical Abstracts (1970-November 2010) was performed using the terms vancomycin, neutropenia, and leukopenia. Citations from publications were reviewed for additional references.

STUDY SELECTION AND DATA EXTRACTION

Studies and case reports were included if they reported neutropenia with vancomycin administration and excluded if they did not describe vancomycin dosages and/or concentrations, or if neutropenia resolved while the patient was still receiving vancomycin. Cases with significant confounders and those in which authors provided minimal information about patients were also excluded.

DATA SYNTHESIS

Seven retrospective chart reviews (ie, case series) and 33 case reports were identified. Of these, 3 retrospective reviews and 26 case reports met inclusion criteria. To our knowledge, no prospective studies have assessed this clinical complication. Data suggest that vancomycin-induced neutropenia may not be completely related to daily dosages, total cumulative dosage, or supratherapeutic vancomycin concentrations. Furthermore, evidence suggests that neutropenia is more likely associated with therapy longer than 7 days, with the majority of episodes occurring beyond 20 days of therapy. Given these findings, a practical approach is to monitor white blood cell (WBC) count with a differential (including absolute neutrophil count) once a week in patients who are receiving vancomycin for more than 7 days.

CONCLUSIONS

Vancomycin-induced neutropenia is most likely associated with prolonged vancomycin exposure. Patients receiving vancomycin for longer than 7 days should have WBC count, differential, monitored weekly. Vancomycin should be discontinued if there is a high clinical suspicion of it causing neutropenia, and an alternative agent should be initiated. Prospective case-controlled studies are needed to better characterize this adverse event.