Trimethoprim-Sulfamethoxazole Associated Drug-Induced Liver Injury in Pediatrics: A Systematic Review.

Abstract

Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population. PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies. A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report. Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.