#11: Metronidazole for the Treatment of Norovirus in Transplant Recipients

Abstract Background Norovirus is a common cause of gastroenteritis in both immunocompetent and immunocompromised hosts. In transplant recipients, it can lead to prolonged shedding and chronic diarrhea. Treatment with nitazoxanide, oral immunoglobulin, or mammalian target of rapamycin (mTOR) inhibitors have shown varying degrees of benefit in small studies. The commensal gastrointestinal bacterial flora may influence the pathogenesis of norovirus infection. Metronidazole is often used to modulate gastrointestinal flora, and improvement of an HIV patient with suspected Giardia infection subsequently identified to have norovirus suggested a possible use of this drug for other immune-suppressed patients with norovirus infection. Methods Solid-organ or stem cell transplant recipients testing positive for norovirus in stool from July 2014 to March 2019 were identified from the medical record. Patient characteristics, laboratory data, and medications were systematically reviewed to identify factors associated with clinical improvement. Results Thirty-eight patients met inclusion criteria. Almost 75% of the patients were male. Almost 80% of the patients were solid-organ transplant recipients: 40% heart, 24% kidney, and 15% liver. There were 85 positive norovirus tests among the 38 patients. Of these, 14 involved coinfections with another potential pathogen: 11 with adenovirus, 2 with Clostridioides difficile, and 1 with cytomegalovirus. In 25 of the 85 positive norovirus tests, nitazoxanide was given. Clinical improvement was documented in 15 of these episodes (60%), while no improvement was observed in 10 (40%). Eight positive tests were treated with metronidazole alone, with documented improvement observed during 6 (75%) courses. In 9 additional episodes, metronidazole was given within a week of the test result and 2 of these had improvement. When other antibiotics were used concurrently with metronidazole, 78% of episodes (7/9) did not lead to clinical response. Changes in immunosuppression were used for the treatment of 6 episodes, leading to clinical improvement in 5. Conclusion Metronidazole treatment was associated with clinical improvement of norovirus gastroenteritis in transplant recipients at rates similar to those seen with nitazoxanide therapy. Reduction in immunosuppression also led to clinical improvement but in situations where that cannot be done safely, metronidazole may be an alternative to nitazoxanide. In this cohort, metronidazole was only used as a therapy after nitazoxanide, suggesting that a trial of metronidazole as rescue therapy in comparison to a repeat course of nitazoxanide after the initial failure of nitazoxanide is justified.