Pyrogenic reactions associated with single daily dosing of intravenous gentamicin.

Objective: To identify risk factors associated with an unexpected outbreak of pyrogenic reactions (PR) following intravenous gentamicin. Design: We conducted two cohort studies. PRs were defined as chills, rigors, or shaking within 3 hours after initiating the gentamicin infusion during the preepidemic (December 1, 1997-January 15,1998) or epidemic (May 1-June 15,1998) periods. We tested gentamicin vials for endotoxin using the limulus amebocyte lysate assay. Setting: Inpatient services of a large community hospital in Los Angeles, California. Results: During the epidemic period, 22 (15%) of 152 patients developed documented PRs following intravenous gentamicin. PRs were more likely among patients receiving single daily dosing (SDD) than multiple daily dosing gentamicin (20/73 [27%] vs 2/79 [3%]; relative risk, 10.8; 95% confidence interval, 2.644.7). Laboratory analysis of gentamicin vials found endotoxin levels that were higher among Fujisawa-brand gentamicin (implicated brand) than gentamicin used after the outbreak terminated (non-implicated brand). Although endotoxin levels in the vials did not exceed US Pharmacopeia limits (1.7 endotoxin units/mg gentamicin), the use of SDD gentamicin may place patients at greater risk of receiving doses of endotoxin above the threshold for PRs in humans. Conclusions: Reassessment of the acceptable amounts of endotoxin in gentamicin and other parenteral products should be considered when dosing intervals used in clinical practice change.