Tigecycline for the Treatments of Severe Clostridioides difficile Infection in Pediatric Immunocompromised Patients

To the Editors: In June 2024, Patel et al updated guideline for managing Clostridioides difficile infection (CDI) in pediatric cancer and hematopoietic cell transplantation patients.1 We recently observed a severe CDI in a 13-year-old girl with acute lymphoblastic leukemia who developed marked oral and gastrointestinal mucositis following high-dose methotrexate. The guideline recommended oral vancomycin or fidaxomicin for severe CDI. However, her profound oral mucositis precluded drug swallowing, and extensive gastrointestinal mucositis hindered medication delivery via nasogastric tube or enema, as recommended by European adult guidelines.2 Furthermore, the pediatric guidelines did not propose a valid intravenous (IV) alternative.1 A critically appraised topic review3 identified IV tigecycline as a potential option for severe CDI, though its role remains debated due to a lack of randomized clinical trials. European adult guideline suggests IV tigecycline for patients with deteriorating CDI or when luminal concentrations of primary agents are suboptimal (weak recommendations and very low-quality evidence).2 IV metronidazole is another suggested alternative or adjunct; however, studies have linked it with higher mortality compared with oral or tigecycline therapy. Tigecycline is primarily eliminated through biliary and fecal excretion, with approximately 59% of the dose recovered in feces.4 Studies have shown tigecycline exhibits significant activity against C. difficile, with low minimum inhibitory concentrations. Additionally, tigecycline suppresses toxin production and reduces spore formation in C. difficile strains in a dose-dependent manner.4 Although data on tigecycline’s efficacy against CDI are limited, clinical case reports and retrospective analyses are encouraging. Successful treatment of severe or refractory CDI with tigecycline, especially when standard therapies failed, has been documented. Improvement is often observed within a week of initiating tigecycline therapy, with no relapses reported during follow-up.4 Concerns over tigecycline’s safety have been a barrier to its widespread use in children. Historically, its association with permanent tooth discoloration and a black-box warning from the Food and Drug Administration (FDA) regarding higher mortality rates compared with other antibiotics limited its application. However, these risks were later attributed to its bacteriostatic properties and complex pharmacokinetics in bacteremic or pulmonary infections. Subsequently, data supported tigecycline’s safety and efficacy in multidrug-resistant infections, leading to its approval by the European Medicines Agency for children older than 8 years.5 In conclusion, tigecycline’s biliary excretion and proven activity against C. difficile suggest that it may serve as a viable alternative for severe CDI, particularly when oral or topical therapies are contraindicated. This is especially relevant for severely immunocompromised pediatric patients or those in intensive care settings. Based on this data we successfully treated our young patients (weight 31 kg) with 50 mg of tigecycline 2 times a day for 10 days, with resolution of symptoms on day 4 of treatment. However, further randomized clinical trials are essential to establish tigecycline’s definitive role in CDI management.