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.

Colorectal cancer chemotherapy: can sex-specific disparities impact on drug toxicities?

“…Evaluating thrombocytopenia, it is already known that women have a larger platelet count than men [ 25 ]. A recent Japan study on antibiotic-induced thrombocytopenia reports that there is a higher drug-induced thrombocytopenia in male patients treated with six different drugs, compared with females [ 26 ], as we report for topoisomerase inhibitor and DNA binding drugs. In addition, we observed that the female sex is a negative predictor of dysgeusia in those undergoing topoisomerase inhibitor, growth inhibitor, and monoclonal antibody chemotherapy.…”

An Updated Comprehensive Pharmacovigilance Study of Drug‐Induced Thrombocytopenia Based on FDA Adverse Event Reporting System Data

“…The mechanisms of thrombocytopenia associated with many drugs remain unknown, which creates additional challenges in managing DIT clinically. 12,13 Therefore, the identification of drugs associated with thrombocytopenia is crucial before establishing an appropriate management plan. Certain cases of DIT can only be detected through long-term monitoring, and so clinical trails might not be the best study design.…”

“…Yuki Asai et al analyzed the relationship between antibacterial drugs and thrombocytopenia using JADER, and revealed the profiles of DIT and 12 antibiotics. 18 Emily Jane Woo et al discovered the increased risk of thrombocytopenia associated with the Ad.26.COV2.S COVID-19 vaccine based on Vaccine Adverse Event Reporting System (VAERS) data. 19 Go Ando et al used both JADRS and FAERS to identify an association between ganciclovir and thrombocytopenia.…”

“…The primary challenge in the management of DIT is identifying the specific drug that contributed to thrombocytopenia. The mechanisms of thrombocytopenia associated with many drugs remain unknown, which creates additional challenges in managing DIT clinically 12,13 . Therefore, the identification of drugs associated with thrombocytopenia is crucial before establishing an appropriate management plan.…”

“…Studies on DIT based on AERS data have been reported. Yuki Asai et al analyzed the relationship between antibacterial drugs and thrombocytopenia using JADER, and revealed the profiles of DIT and 12 antibiotics 18 . Emily Jane Woo et al discovered the increased risk of thrombocytopenia associated with the Ad.26.COV2.S COVID‐19 vaccine based on Vaccine Adverse Event Reporting System (VAERS) data 19 .…”