Metronidazole, Vancomycin Recommended for C Difficile in Pediatric Oncology, HSCT

An international multidisciplinary panel presented recommendations for the use of metronidazole or vancomycin in the treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), as well as other recommendations for prevention and treatment of CDI in these patients, in a report published in the Journal of Clinical Oncology.

C difficile is a common bacteria in normal GI flora; however, rates of CDI in adults and children are increasing. Risk factors include recent antibiotic and chemotherapy exposure and prolonged hospitalization, all of which are common in pediatric patients with cancer and those undergoing HSCT. As a result, CDI is now the most common cause of healthcare-associated infectious diarrhea and an important healthcare-associated infection in pediatric patients.

Although several guidelines are established for managing this infection, none focus on pediatric patients in these clinical settings. Therefore, an international multidisciplinary panel of pediatric oncology and infectious diseases experts sought to develop a clinical practice guideline (CPG) for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients.

The panel performed systematic reviews of randomized controlled trials that focused on prevention or treatment of CDI in any population then considered the applicability of the findings to pediatric cancer and HSCT patient populations. The review identified 63 papers, reporting on 65 randomized studies. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to generate the recommendations. Despite the low-quality of evidence specific to children and adolescents with cancer and pediatric HSCT patients in these studies, the panel made the following 7 recommendations:

• Probiotics are not recommended for routine prevention of CDI (weak recommendation).
• Oral metronidazole or oral vancomycin should be used to treat nonsevere CDI (strong recommendation).
• Oral vancomycin should be used to treat severe CDI (strong recommendation).
• Fidaxomicin should be considered for the treatment of recurrent CDI (weak recommendation).
• Fecal microbiota transfer (FMT) should not be routinely used in the treatment of CDI (strong recommendation).
• Monoclonal antibodies should not be used routinely to treat CDI (weak recommendation).
• Probiotics are also not recommended for treatment of CDI (weak recommendation).

“Children who receive cancer therapies will differ from adults with cancer and immunocompetent children in terms of antibiotic exposure, concomitant medications, and comorbidities,” the researchers noted in their report. The omission of pediatric patients from randomized trials on prevention and treatment of CDI resulted in a lack of high-quality evidence to inform these recommendations. Therefore, the researchers suggest future trials focus exclusively on pediatric patients or include sufficient numbers of them in adult trials.

Reference

Diorio C, Robinson PD, Ammann RA, et al. Guideline for the management of Clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients [published online September 14, 2018]. J Clin Oncol. doi: 10.1200/JCO.18.00407