Short Course Cefixime to Prevent Irinotecan-Associated Diarrhea in Children With Solid Tumors: A Retrospective...

Prophylactic administration of oral third-generation cephalosporins, administered prior to and concurrently with irinotecan, reduces dose-limiting diarrhea and allows higher irinotecan dosing in pediatric patients. The Children's Oncology Group recommends a 10-day cefixime regimen, beginning 2 days prior to irinotecan, continuing throughout the 5-day irinotecan course, and concluding 3 days afterward. Despite its efficacy, compliance with this regimen presents significant logistical challenges. To address these challenges, a multidisciplinary team at St. Jude Children's Research Hospital instituted a standardized 5-day prophylactic regimen in patients receiving irinotecan. This study compared the incidence of severe diarrhea during the first course of irinotecan before and after the implementation of a shortened 5-day course of cefixime.

A single-center retrospective cohort study was performed for patients who received a 5-day course of irinotecan during the 12 months before and 18 months after implementation of a shortened cefixime prophylaxis regimen. The primary outcome was the incidence of severe diarrhea. Secondary outcomes included provider ordering compliance with prophylactic antibiotic recommendations, the duration of prophylactic antibiotics, and the incidence of Clostridioides difficile infections or ceftriaxone-resistant gram-negative bacterial infections.

Data were collected for 85 participants (35 pre-implementation and 50 in the post-implementation period), representing a total of 432 irinotecan courses. Eighty-two percent of courses included intravenous irinotecan. The incidence of severe diarrhea was 5.4% in the pre- and 6.2% in the post-implementation period (p = 0.7255). Provider ordering compliance with the institutional standard improved from 7.2% to 68.4% (p < 0.0001). Three patients developed a C. difficile infection, while no patients developed a microbiologically documented ceftriaxone-resistant gram-negative bacterial infection.

A 5-day course of prophylactic cefixime, starting on the day of irinotecan initiation, was safe, increased provider ordering compliance, and did not lead to increased irinotecan toxicity.