Adverse events associated with prolonged antibiotic use.

PURPOSE: The Infectious Diseases Society of America and US CDC recommend 60 days of ciprofloxacin, doxycycline, or amoxicillin for anthrax prophylaxis. It is not possible to determine severe adverse drug event (ADE) risks from the few people thus far exposed to anthrax prophylaxis. This study's objective was to estimate risks of severe ADEs associated with long-term ciprofloxacin, doxycycline, and amoxicillin exposure using three large databases: one electronic medical record (General Practice Research Database) and two claims databases (UnitedHealthcare, HMO Research Network).

METHODS

We include office visit, hospital admission and prescription data for 1/1/1999-6/30/2001. Exposure variable was oral antibiotic person-days (pds). Primary outcome was hospitalization during exposure with ADE diagnoses: anaphylaxis, phototoxicity, hepatotoxicity, nephrotoxicity, seizures, ventricular arrhythmia, or infectious colitis.

RESULTS

We randomly sampled 999,773, 1047,496, and 1819,004 patients from Databases A, B, and C respectively. 33,183 amoxicillin, 15,250 ciprofloxacin and 50,171 doxycycline prescriptions continued > or =30 days. ADE hospitalizations during long-term exposure were not observed in Database A. ADEs during long-term amoxicillin were seen only in Database C with 5 ADEs or 1.2(0.4-2.7) ADEs/100,000 pds exposure. Long-term ciprofloxacin showed 3 and 4 ADEs with 5.7(1.2-16.6) and 3.5(1.0-9.0) ADEs/100,000 pds in Databases B and C, respectively. Only Database B had ADEs during long-term doxycycline with 3 ADEs or 0.9(0.2-2.6) ADEs/100,000 pds. For most events, the incidence rate ratio, comparing >28 versus 1-28 pds exposure was <1, showing limited evidence for cumulative dose-related ADEs from long-term exposure.

CONCLUSIONS

Long-term amoxicillin, ciprofloxacin, and doxycycline appear safe, supporting use of these medications if needed for large-scale post-exposure anthrax prophylaxis.