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.