Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

Abstract

Drug-induced thrombocytopenia (DITP) can be triggered by antibiotics; however, the details remain unclear. Here, we evaluated the expression profiles of DITP using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of DITP between April 2004 and January 2021 from the JADER database. The reporting odds ratio (ROR) and 95% confidence interval (CI) were used to detect DITP signals. Factors thought to affect DITP, such as male sex and an age of at least 60 years, were added as covariates. We evaluated the time-to-onset profile and hazard type using the Weibull shape parameter. The JADER database contained 1,048,576 reports. Twelve of 60 antibiotics showed signals for DITP; the RORs (95% CIs) for ampicillin/sulbactam, ceftazidime, cefozopran, ciprofloxacin, fluconazole, fos-fluconazole, linezolid, pazufloxacin, piperacillin/tazobactam, teicoplanin, trimethoprim/sulfamethoxazole, and voriconazole were 1.75 (1.41-2.16), 1.77 (1.42-2.18), 1.35 (1.06-1.72), 2.56 (2.19-2.98), 1.93 (1.67-2.23), 2.08 (1.76-2.46), 5.29 (2.73-9.60), 1.92 (1.51-2.41), 1.54 (1.05-2.19), 1.47 (1.16-1.84), 1.92 (1.73-2.14), and 2.32 (1.59-3.30), respectively. In multiple logistic regression analysis, 7 and 6 antibiotics were detected for the factors age and male sex, respectively. The median times-to-onset of DITP for ciprofloxacin (oral treatment), fluconazole, linezolid, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole were 91, 91, 11.5, 10, and 9 days, respectively. Furthermore, the 95% CI of the Weibull shape parameter β for these antibiotics was above and excluded 1, indicating that the antibiotics were the wear out failure type. We revealed the expression profiles of DITP following treatment with 12 antibiotics.