Nitazoxanide Is a Therapeutic Option for Adenovirus-Related Enteritis in Immunocompromised Adults

Abstract

T he clinical efficacy of cidofovir for the treatment of adenovirus-related disease is limited, and toxicity is a major concern. Furthermore, pharmacokinetic limitations such as poor bioavailability lead to an insufficient fidelity between the prescribed dose and the pharmacodynamics effects. Nitazoxanide, an agent with broad antiviral activity and less toxicity, may be a consideration for non-life-threatening adenovirus-related enteritis/colitis. Moreover, different from the virus-targeted mechanisms of other therapies, the mechanism of nitazoxanide and tizoxanide, the active metabolite, involves the disruption of host-regulated pathways involved in viral replication (1-3). This mechanistic nuance limits the viral resistance for nitazoxanide. We present a case of an immunocompromised adult with adenovirus-related diarrhea and low-level viremia who was successfully treated with nitazoxanide.A 61-year-old patient was hospitalized at our institution with a 2-week history of nonbloody diarrhea. The patient's history included relapsed multiple myeloma diagnosed in 2015, after autologous hematopoietic stem cell transplant, and treatment with daratumumab, pomalidomide, and dexamethasone, with the latest treatment 1 month prior to the index admission. All of the other systems reviewed were negative. The patient reported there had been no recent travel, contact with sick individuals, or exposure to contaminated water/food. The physical exam revealed an increased heart rate of 101 beats/min, normal systolic blood pressure, and a temperature of 37.7°C. The patient appeared dehydrated and lethargic, and an abdominal exam revealed hyperactive bowel sounds with no pain, guarding, or hepatosplenomegaly. A laboratory evaluation revealed a normal white blood cell count of 7.5 ϫ 10 9 cells/liter, with no abnormalities on a differential cell count. However, both CD3 (547 cells/l) and CD4 (180 cells/l) cell counts were low. A metabolic profile indicated acute kidney injury, with a serum creatinine (Cr) level of 1.9 mg/dl, up from a baseline Cr of 1.5 mg/dl. Other electrolyte derangements included hypokalemia (2.7 mmol/liter) and mild hypomagnesemia (1.6 mg/dl). The liver enzyme levels were unremarkable, and a gastrointestinal pathogen multiplex PCR panel was negative for Clostridium difficile toxin B but positive for adenovirus F40/41. This prompted an evaluation of adenovirus in plasma samples via quantitative real-time PCR, which returned a positive result with 3,671 copies/ml (reference, Ͻ500 copies/ml). An X ray of the abdomen showed no signs of obstruction or free air. The patient underwent flex sigmoidoscopy, where a 2-cm sessile polyp in the descending colon was noted. Histopathology demonstrated a normal colonic mucosa, no microscopic colitis, and negative results for cytomegalovirus (CMV) immunostaining.The case was classified as adenovirus viremia with disease symptoms of gastrointestinal involvement. In consideration of the hemodynamic stability, the low risk for disseminated disease, and the impaired renal function, an ...

Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?

“…Interestingly, the patient recovered from diarrhea after 48 h of treatment. It is notable that the limited toxicity and viral resistance of NTZ, as well as the few drug interactions, make it a promising treatment option for such infections [15].…”

Disseminated adenovirus infection after autologous stem cell transplant

“…Brincidofovir has demonstrated greater bioavailability and less nephrotoxicity than cidofovir in phase 1‐2 trials, but is associated with higher rates of diarrhea and is neither FDA approved nor currently commercially available except through clinical trials . Nitazoxanide's success in treating disseminated AdV has been limited to case reports, as such additional data are needed before its widespread use …”

“…9 Nitazoxanide's success in treating disseminated AdV has been limited to case reports, as such additional data are needed before its widespread use. 10,11 In conclusion, disseminated AdV infection is a rare complication after autologous hematopoietic stem cell transplant, but should be considered in patients receiving ATG conditioning regimens. Fortunately, as in our patient's case, cidofovir, in addition to reducing immunosuppression, can be used to successfully treat disseminated or tissue invasive AdV disease even in patients after autologous hematopoietic stem cell transplant.…”

Next-Generation Phenotypic Screening in Early Drug Discovery for Infectious Diseases

“…Indeed, NTZ displays strikingly wider anti-infective efficacy than was expected, or even sought, upon its discovery [32]. Today, NTZ is revealed to be active against a range of extracellular and intracellular protozoans [33,34], helminths [35], anaerobic and microaerophilic bacteria [36,37], and viruses [38][39][40][41][42][43][44][45], including a broad range of respiratory viruses [46,47], and even neoplastic cells [48]. At least one recent report claims successful clinical treatment of cutaneous leishmaniasis with oral nitazoxanide [49].…”