Comprehensive Analysis of Antibiotic-induced Agranulocytosis Using the Japanese Adverse Drug Event Report Database

Abstract

Although infrequent, drug-induced agranulocytosis can be stimulated by antibiotics. Here, we analyzed the Japanese Adverse Drug Event Report database to identify profiles of antibiotic-induced agranulocytosis. Ten of 60 antibiotics showed signals for agranulocytosis; the reporting odds ratios (95% confidence intervals) for ampicillin/sulbactam, amikacin, cefmetazole, cefozopran, clindamycin, ciprofloxacin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 2.65 (1.79–3.80), 2.49 (1.91–4.34), 4.48 (2.27–6.92), 2.77 (1.88–3.95), 1.64 (1.04–2.47), 2.01 (1.40–2.82), 2.78 (2.11–3.60), 6.05 (2.16–13.7), 2.05 (1.31–3.07), and 3.54 (2.73–4.54), respectively. The median times-to-onset of agranulocytosis for ampicillin/sulbactam, cefmetazole, cefozopran, clindamycin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 20, 6, 10, 16, 12, 3, 18, and 13 days, respectively. The 95% confidence intervals of the Weibull shape parameter β for these antibiotics were over and excluded 1, indicating that the antibiotics were the wear out failure type. These findings provided insights into the characteristics of antibiotic-induced agranulocytosis.