1. Laboratory of Drug Informatics, Gifu Pharmaceutical University; Gifu, Japan.
2. Department of pharmacy, Kobe City Medical Center General Hospital; Kobe, Japan.
3. Laboratory of Community Pharmacy, Gifu Pharmaceutical University; Gifu, Japan.
4. Current address: Division of Pharmacy, Nara Medical University Hospital, 840, Shijocho, Kashihara-shi, Nara, 634-8522, Japan.
5. Current address: Division of Pharmacy, Kyoto City Hospital, 1-2, Mibu Higashitakadacho, Nakagyo-ku Kyoto-shi, Kyoto, 604-8845, Japan.
Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database.
Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter.
Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68).
Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.
Keywords: Clostridium difficile-associated colitis, anti-infective, adverse event, JADER