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-Jun e 15, 1998) periods. We tested gentamicin vials for endotoxin using the lim ulus amebocyte lysate assay. SETTING: Inpatient services of a large community hospital in Los Angeles, C alifornia. RESULTS: During the epidemic period, 22 (15%) of 152 patients developed doc umented PRs following intravenous gen tamicin. PRs were more likely among p atients receiving single daily dosing (SDD) than multiple daily dosing gent amicin (20/73 [27%] vs 2/79 [3%]; relative risk, 10.8; 95% confidence inter val, 2.6-44.7). Laboratory analysis of gentamicin vials found endotoxin lev els that were higher among Fujisawa-brand gentamicin (implicated brand) tha n gentamicin used after the outbreak terminated (non-implicated brand). Alt hough endotoxin levels in the vials did not exceed US Pharmacopeia limits ( 1.7 endotoxin units/mg gentamicin), the use of SDD gentamicin may place pat ients at greater risk of receiving doses of endotoxin above the threshold f or PRs in humans.. CONCLUSIONS: Reassessment of the acceptable amounts of endotoxin in gentami cin and other parenteral products should be considered when dosing interval s used in clinical practice change.