Evaluation of anti-infective-related Clostridium difficile-associated colitis using the Japanese Adverse Drug Event Report database.

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.