Use Of Nitazoxanide Research Articles

Higher biodegradation rate of atrazine by Paenarthrobacter sp. KN0901 with P-doped hydrochar: The important role of biofilm regulated by autoinducer-2 regulated quorum sensing during the degradation process

The presence of atrazine residue in runoff from agricultural areas poses a significant risk to the ecosystem. This study aimed to develop microorganism-material systems using the atrazine-degrading strain Paenarthrobacter sp. KN0901 and P-doped hydrochar to effectively remove atrazine residues from aquatic environments. The atrazine degradation rate increased by 22.6 % with the addition of P-doped hydrochar after three days of incubation at 15 °C. Autoinducer-2 activity increased from 100 % to 116.7 % with P-doped hydrochar addition, indicating improved quorum sensing compared to free microorganisms. The extracellular polymeric substance content was significantly higher in the PHC groups compared to the blank groups, suggesting enhanced biofilm formation. Quorum sensing was inhibited by the use of nitazoxanide and sodium nitroprusside, leading to decreased atrazine degradation. In contrast, the presence of glucose and S-adenosyl methionine enhanced the rate of atrazine degradation due to elevated quorum sensing. These results suggested that P-doped hydrochar enhanced strain KN0901′s ability to assemble, increasing quorum sensing and accelerating atrazine degradation. Additionally, P-doped hydrochar promoted atrazine degradation by strain KN0901 under various conditions by enhancing quorum sensing. This work offers a new perspective on developing and using bioremediation techniques to remediate atrazine-contaminated environments under diverse conditions.

Pharmacological efficacy and potential of the use of nitazoxanide, a thiazolide drug with a wide spectrum of action

The article is devoted to the possibility and prospects of using nitazoxanide in a wide range of diseases. Based on literature data, the authors evaluate the pharmacological effectiveness and substantiate the potential of using nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. This information is of interest and can be used to decide on the need to conduct clinical trials of nitazoxanide in Russia. A systematic search for current information was conducted in four databases until December 1, 2023: PubMed, EMBASE, Web of Science and Cochrane Library. The work included preclinical studies in vitro and in vivo, as well as randomized clinical trials comparing the pharmacological effectiveness of nitazoxanide and placebo. The broad-spectrum thiazolide drug nitazoxanide has antibacterial, antiprotozoal, anthelmintic, antiviral and antitumor activity. This is achieved through its pharmacological properties, namely: regulation of the cell cycle, apoptosis, cell proliferation and migration; activation of innate immunity; influence on the synthesis and activation of cell proteins, some of which are links in cellular signaling pathways; binding to proteins of viruses, bacteria, protozoa and helminths with disruption of their vital functions; immunomodulating effect by regulating the activity of pro- and anti-inflammatory cytokines. The article systematizes and summarizes current information on the pharmacodynamics of nitazoxanide, as well as the results of preclinical and clinical studies of the drug, and discusses further prospects.

Efficacy of a single dose of nitazoxanide in dogs naturally infected with Giardia duodenalis

Giardia duodenalis is a protozoan parasite that infects many mammals, including dogs and cats. This waterborne and foodborne zoonosis is a major problem in one health. Treatment can be challenging because of long regimens and drug resistance. The objective of this study was to evaluate the efficacy of single-dose nitazoxanide (NTZ) for dogs naturally infected by Giardia duodenalis. Although widely used in humans, pharmacological safety is incipient, since the approval of the safe use of nitaxozanide for dogs is not a consensus in the world. Fifty dogs diagnosed with G. duodenalis by zinc sulfate flotation technique (Faust method) and cysts detection by light microscopy. Half of the animals received a dose of 50 mg/kg of NTZ and the other half received 3 doses of 50 mg/kg of fenbendazole (FBZ), both orally. One week after treatment, new fecal exams were done to prove the effectiveness. Of the animals treated with NTZ, 84% were negative for the protozoan, while 76% of the animals treated with FBZ were negative, no significant difference was identified. Side effects such as vomiting and hyporexia were manageable in NTZ treatment and no changes in laboratory tests showed hepatic or renal impairment. We conclude that the use of NTZ in a single dose of 50 mg/kg is effective for canine giardiasis, constituting an option to be considered for dogs with relapses, poor response to conventional drugs and to facilitate administration regimens.

Outpatient treatment of COVID-19: an experience with 552 cases in Mexico.

The impact of the coronavirus disease 2019 (COVID-19) pandemic has globally challenged health services, especially because when the pandemic first reached Mexico, in February 2020, there was no known effective and safe treatment. A treatment scheme was offered by the Institute for the Integral Development of Health (IDISA) in Mexico City from March 2020 to August 2021 when there were many patients with COVID-19. This report summarizes the experience managing COVID-19 with this scheme. This is a descriptive, retrolective study. The data was obtained from the case files of the patients who attended the IDISA from March 2020 to August 2021 with COVID-19. All the cases were treated with the scheme consisting of nitazoxanide, azithromycin, and prednisone. Various laboratory blood tests and chest computerized tomography scan were done. When indicated, supplementary oxygen, and another specific treatment were used. A standardized clinical recording was conducted for 20 days based on symptoms and systemic symptoms. Based on the World Health Organization criteria, the patients were classified according to the disease severity: 170 mild, 70 moderate, and 312 severe cases. The outcome was the discharge of 533 patients after their recovery, 16 were excluded from the study, and 6 died. The use of nitazoxanide, azithromycin, and prednisone proved to be effective as it resulted in improvement of symptoms and in successful outcomes for the management of COVID-19 outpatients.

Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials

PurposeNitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19.MethodsSearches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI).ResultsFive blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = − 0.16; 95% CI − 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = − 0.15; 95% − 0.29 to − 0.02), lactate dehydrogenase (LDH) (SMD − 0.32; 95% − 0.52 to − 0.13), and D-dimer (SMD − 0.49; 95% CI − 0.68 to − 0.31) compared to placebo, but the magnitude of effect was considered small to moderate.ConclusionThis systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00228-022-03380-5.

Haw’s Syndrome Associated with Giardiasis in a Cat

Background: Haw’s syndrome results in bilateral projection of the third eyelid, which is caused by a dysfunction of the sympathetic innervation in the region, not accompanied by other ocular changes. It has been mostly seen in cats, under 2-year-old and, it usually shows an acute presentation. It is believed that the disorder may be self-limiting, but several infectious etiologies have been proposed, together with diarrhea. The aim of the study was to report a case of a 2-year-old mixed breed male feline, castrated and diagnosed with Haw’s syndrome, associated with an infectious condition given the presence of Giardia sp.Case: A 2-year-old male, mixed-breed cat and orchiectomized, was admitted and treated at the Veterinary Hospital of the Federal University of Jataí. In the anamnesis, the owner complained that the cat had had pasty brown diarrhea for 4 days and a projection of the third eyelid. He emphasized that the animal used to have some episodes of diarrhea sporadically and the last deworming was carried out 3 months ago from that day. He reported contact with other random street and outdoorcats. On the physical examination, bilateral projection of the third eyelid was observed without any other visible alteration. The third eyelid projection was responsive to the mydriatic and adrenergic [phenylephrine 10%] eye drops instillation test. Complete blood count and serum biochemical evaluation of creatinine, alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations were performed. In addition, abdominal ultrasound and parasitological examination of feces were requested. Complete blood count showed eosinophilia and serum biochemical evaluations were within reference values. The coproparasitological examination detected Giardia sp. On the ultrasound, no significant changes were observed. The recommended treatment was anthelmintic [fenbendazole 50 mg/kg, SID, for 5 days]. However, one week later, the coproparasitological examination still showed Giardia sp. Given this scenario, the chosen treatment was the use of nitazoxanide [25 mg/kg, BID, for 7 days]. Therefore, the patient presented emesis and the treatment with nitazoxanide had to be suspended. Thus, metronidazole [25 mg/kg, BID, for 7 days] was prescribed, in addition to the environmental disinfection and daily litter box cleaning, all performed with quaternary ammonia. After 1 week of treatment with metronidazole, the patient’s clinical improvement and reversal of the third eyelid projection were observed.Discussion: This case proved to be consistent with the data found in the literature, in which cats younger than 2-year-old are affected by Haw’s syndrome and may present concomitant diarrhea. On the physical examination, the parameters evaluated were within normal reference for the cat species and the bilateral projection of the third eyelid was the only alteration found in the patient. The prognosis for the patient with Haw’s syndrome and concomitant giardiasis is favorable, as longas the intestinal infection is treated briefly, in order to prevent the chronicity of the enteroparasitosis. The need of more studies is evident in order to explain the Haw’s syndrome pathology and so, clarify the real cause of this disease. Since the syndrome is mostly, a self-limiting disease, interventions with topical ocular drugs are not necessary. However, in the event of a concomitant disease, infection or underlying cause, it must be treated correctly. Attention is drawn to the need of feces examination through coproparasitological evaluation in cases of diarrhea. Keywords: cat, diarrhea, intestinal parasitosis, nict membrane.

NITAZOXANIDE IN TREATMENT OF ROTAVIRUS DIARRHEA IN CHILDREN: A SINGLE CENTER STUDY

BACKGROUND & OBJECTIVE: As Rota virus leads to significant morbidity in children 2 months to 5 years, this study was done to observe the effect of one dose of nitazoxanide on the total duration of rotavirus diarrhea. The primary objective was to evaluate the reduction in the mean duration of viral diarrhea in children after administration of first dose of Nitazoxanide.
 METHODLOGY: This descriptive study was done in the Department of Pediatric Medicine Unit I, Mayo Hospital, Lahore from Jan 2016 to June 2016 after approval from the ethical review committee. Sample size calculated was 175 using WHO sample size calculator. Patients of 4–5 years were given 200 mg nitazoxanide twice daily for 3 days; 100 mg nitazoxanide was given twice daily to 12–47 months age group, and patient of <12 months age were given 7.5 mg/kg twice day along with routine care and were followed 12 hourly till the passage of normally formed stools. Duration of diarrhea was recorded.
 RESULTS: Out of 175 cases, 58.9% (n=103) were between 2-36 months age while 41.2% (n=72) were 37-60 months age, mean+SD was calculated as 35.06+13.34 months, mean reduction in duration of rotavirus diarrhea in children after administration of first dose of Nitazoxanide was recorded as 32.85+2.32 hours.
 CONCLUSION: With the use of nitazoxanide along with routine care for rotavirus diarrhea children, the mean duration of rotavirus diarrhea was reported to be less than 1.5 days.

Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient settings significantly improved COVID-19 outcomes compared to known outcomes in untreated patients

In a prospective observational study (pre-AndroCoV Trial), the use of nitazoxanide, ivermectin and hydroxychloroquine demonstrated unexpected improvements in COVID-19 outcomes when compared to untreated patients. The apparent yet likely positive results raised ethical concerns on the employment of further full placebo controlled studies in early-stage COVID-19. The present analysis aimed to elucidate, through a comparative analysis with two control groups, whether full placebo-control randomized clinical trials (RCTs) on early-stage COVID-19 are still ethically acceptable. The Active group (AG) consisted of patients enrolled in the Pre-AndroCoV-Trial (n = 585). Control Group 1 (CG1) consisted of a retrospectively obtained group of untreated patients of the same population (n = 137), and Control Group 2 (CG2) resulted from a precise prediction of clinical outcomes based on a thorough and structured review of indexed articles and official statements. Patients were matched for sex, age, comorbidities and disease severity at baseline. Compared to CG1 and CG2, AG showed reduction of 31.5–36.5% in viral shedding (p < 0.0001), 70–85% in disease duration (p < 0.0001), and 100% in respiratory complications, hospitalization, mechanical ventilation, deaths and post-COVID manifestations (p < 0.0001 for all). For every 1000 confirmed cases for COVID-19, at least 70 hospitalizations, 50 mechanical ventilations and five deaths were prevented. Benefits from the combination of early COVID-19 detection and early pharmacological approaches were consistent and overwhelming when compared to untreated groups, which, together with the well-established safety profile of the drug combinations tested in the Pre-AndroCoV Trial, precluded our study from continuing employing full placebo in early COVID-19.

Nitazoxanide as an early treatment to reduce the intensity of COVID‑19 outbreaks among health personnel

The use of nitazoxanide has previously yielded successful results <em>in vitro</em> against the coronavirus. The aim of the present study was to examine the efficacy of the use of nitazoxanide at an early stage among healthcare workers exhibiting symptoms of COVID‑19. This was a prospective study carried out in 2020. Healthcare personnel who presented with COVID‑19 symptoms, in different 3 hospitals were invited to take Paramix (nitazoxanide), 500 mg orally, every 6 h for 2 days and then 500 mg twice a day for 4 days. To compare the hospitalization percentage, a group of healthcare workers with a respiratory viral infection without COVID‑19 criteria were also followed‑up. Over a period of 3 months, 150 healthcare workers (111 women and 39 men) presented respiratory symptoms with COVID‑19 criteria (mean age, 36±10.6 years; range, 18‑68 years). Only one female medical doctor, one nurse and one male from the auxiliary services had to be hospitalized and one death was registered It was thus concluded that nitazoxanide yielded successful results <em>in vitro</em> against previous coronavirus and may prove to be useful against SARS‑CoV‑2 as an early intervention to avoid complications, decreasing the expected number of hospitalizations among infected healthcare workers.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BackgroundNitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsIn a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed.ResultsFrom June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4–5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed.ConclusionsIn patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Abordagem profilática da nitazoxanida e ivermectina na COVID-19: Sumário de Evidências

Objective: To identify evidence regarding the preventive approach and outpatient use of the use of nitazoxanide, ivermectin and hydroxychloroquine in COVID-19. Methods: Summary of evidence with search performed at Pubmed and Medrxiv. In the absence of studies on preventive and outpatient use, the mechanism of action of the medication was explained. Results: The number of studies that address the prophilatic use is low. Three articles on nitazoxanide, six on ivermectin and six on hydroxychloroquine were included. Conclusions: The prophylactic use of the medications addressed by the present study should be evaluated in observational studies or randomized clinical trials of good quality.

Host-targeted nitazoxanide has a high barrier to resistance but does not reduce the emergence or proliferation of oseltamivir-resistant influenza viruses in vitro or in vivo when used in combination with oseltamivir

A major limitation of the currently available influenza antivirals is the potential development of drug resistance. The adamantanes, neuraminidase inhibitors, and more recently polymerase inhibitors, have all been associated with the emergence of viral resistance in preclinical, clinical studies or in clinical use. As a result, host-targeted drugs that act on cellular proteins or functions have become an attractive option for influenza treatment as they are less likely to select for resistance. Nitazoxanide (NTZ) is a host-targeted antiviral that is currently in Phase III clinical trials for the treatment of influenza. In this study, we investigated the propensity for circulating influenza viruses to develop resistance to nitazoxanide in vitro by serially passaging viruses under selective pressure. Phenotypic and genotypic analysis of viruses passaged ten times in the presence of up to 20 μM tizoxanide (TIZ; the active metabolite of nitazoxanide) showed that none had a significant change in TIZ susceptibility, and amino acid substitutions arising that were unique to TIZ passaged viruses, did not alter TIZ susceptibility.Combination therapy, particularly utilising drugs with different mechanisms of action, is another option for combatting antiviral resistance, and while combination therapy has been shown to improve antiviral effects, the effect of reducing the emergence and selection of drug-resistant virus has been less widely investigated. Here we examined the use of TIZ in combination with oseltamivir, both in vitro and using the ferret model for influenza infection and found that the combination of the two drugs did not provide significant benefit in reducing the emergence or selection of oseltamivir-resistant virus.These in vitro findings suggest that clinical use of NTZ may be significantly less likely to select for resistance in circulating influenza viruses compared to virus-targeted antivirals, and although the combination of NTZ with oseltamivir did not reduce the emergence of oseltamivir-resistant virus in vitro or in vivo, combination therapy with NTZ and other newer classes of influenza antiviral drugs should be considered due to NTZ's higher host-based barrier to resistance.

Successfully Treated Norovirus- and Sapovirus-Associated Diarrhea in Three Renal Transplant Patients

Objectives To examine the burden of norovirus- and sapovirus-related diarrhea in renal transplant patients and to propose the use of nitazoxanide as a therapeutic option for treatment. Methods We reviewed three renal transplant patients with viral diarrhea requiring hospitalization due to acute renal failure and signs of graft rejection. All three patients were treated with nitazoxanide. We examined their clinical courses after therapy and compared time to resolution of symptoms and viral shedding. Results In all three renal transplant patients, improvement of diarrheal illness was witnessed within one week of nitazoxanide initiation. Conclusions Infectious diarrhea remains an underestimated yet significant cause of morbidity in solid organ transplant patients. Norovirus and sapovirus are often responsible for this presentation. Nitazoxanide was used as a treatment modality with success in reduction of symptoms, decreased duration of illness, and cessation of viral shedding.

578 - Use of Nitazoxanide, an Anti-Parasitic Drug, for Management of Norovirus Ileo-Colitis in an Allogeneic Stem Cell Transplant Patient

Patients undergoing allogeneic stem cell transplant are at significant risk of infections due to the immunosuppression resulting from leukopenia as well as immunosuppressive agents for graft versus host disease prophylaxis or management. Organisms that normally do not result in significant clinical manifestations can cause potentially lethal outcomes in infected allogeneic stem cell transplant patients. Diarrhea resulting from infectious etiology continues to remain a significant complication associated with allogeneic stem cell transplant. Norovirus gastroenteritis is a well described phenomenon in both pediatric as well as adult allogeneic hematopoietic stem cell transplant recipients. There is no definite treatment available for managing this complication and supportive care and withdrawal of immunosuppression continues to remain the mainstay. We report the case of a 68-year-old Caucasian female who underwent a haplo-identical stem cell transplant for high-risk acute myeloid leukemia with FLT3 mutation. The patient developed diarrhea on day+4 and her stool tested positive for Clostridium difficile. Even though she initially responded to appropriate treatment for Clostridium difficile, her diarrhea recurred. Repeat testing for infectious etiology revealed the presence of norovirus while Clostridium difficile was no longer detected. The patient was treated with oral nitazoxanide 500 mg BID for 10 days with significant clinical improvement in her stool volume and frequency as well as consistency. However, she continued to shed the virus even after clinical improvement. Nitazoxanide was developed in 1970 and was initially perceived to be an anti-protozoal agent. An increasing amount of pre-clinical and clinical research has indicated that it is active against a broad variety of organisms including anaerobic gram-positive and gram-negative bacteria, mycobacterium tuberculosis, respiratory viruses as well as rotavirus and norovirus. While there is literature supporting the use of nitazoxanide in other immunosuppressed patients such as HIV infected and solid organ transplant patients, information regarding the safety and efficacy of nitazoxanide for treating norovirus in adult allogeneic stem cell transplant patients is very limited (one case report identified in Pubmed). Our case demonstrates that even in early post-transplant setting, nitazoxanide effectively controlled norovirus gastroenteritis without compromising graft function. The utility of Nitazoxanide in viral gastroenteritis in allogeneic hematopoietic transplant patients should be explored further in prospective trials.Tabled 1Pubmed search using the terms “Nitazoxanide” AND one of the following# of Items in search resultsRelevant to clinical use of Nitazoxanide for Norovirus in Hematopoietic Stem Cell transplantHematopoietic transplant31Stem cell transplant51Norovirus101 Open table in a new tab

Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors.

Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg-1·day-1) or NTZ (200 mg·kg-1·day-1) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012

Australian Indigenous children suffer a high burden of diarrhoeal disease. Nitazoxanide is an antimicrobial that has been shown to be effective against a broad range of enteropathogens. To date, its use has not been reported in the tropical Top End (northernmost part) of the Northern Territory, Australia. The objective was to describe the use of nitazoxanide at the Royal Darwin Hospital, Northern Territory, and to assess any association with the time to resolution of diarrhoea. Eligible children (≤13 years) were identified from dispensary records as having been prescribed nitazoxanide during the audit period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal aetiology, treatment details and clinical outcomes were obtained by chart review. Twenty-eight children were treated with nitazoxanide, mostly for Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was evident in 27 (96%) children on admission, and 11 (41%) were underweight. Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days post-admission). For children ≥12 months, nitazoxanide was prescribed according to guidelines stipulated by the Centers for Disease Control and Prevention (CDC). Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after starting treatment. An increase in weight for length at discharge was found for all children. Prompt resolution of diarrhoea without adverse outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium infection in this setting. Its role in the treatment of other causes of infectious diarrhoea needs further investigation. Randomised trials will further direct its use and determine optimal dosing regimens.

Nitazoxanide use in Rota Viral Diarrhea. Cure or Controversy?

Sir There are numerous unapproved drug formulations available for acute watery diarrhea which promises quick relief of symptoms. The new entrant to that ever-growing list is nitazoxanide. This molecule is being promoted as magical cure for a wide range of enteric infections, not only bacterial but also ‘viral’. The extent to which drug companies push their molecules to the medical fraternity is quite startling. We came across one such campaign in which couple of medical representatives from a leading drug company were indoctrinating the benefits of nitazoxanide in rota-viral diarrhea. They stated that the drug is being used by most of the practicing pediatricians in all viral diarrheas and urged us to do so. They had referenced their claim to a small randomized controlled trial (RCT) published recently [1] and a sentence that appears in the current edition of Nelson’s Text book of Pediatrics, which states that “Nitazoxanide, an anti-infective agent, has been effective in the treatment of a wide variety of pathogens including Cryptosporidum parvum, Giardia lamblia, Entamoeba histolytica, Blastocystis hominis, C. difficile, and rotavirus” which was again based on the same RCT [2]. The study which was being quoted was done in 38 children aged 5 months to 7 years to find the effect of nitazoxanide in rotaviral diarrhea. End point studied was the time from first dose of the drug to resolution of symptoms and was significantly low in children who received a 3 day course of nitazoxanide compared to those who received placebo. The same investigator had also done an analogous study in 50 adult patients with similar results [3]. These results, although promising, cannot by itself be taken as a quality evidence for the use of nitazoxanide in rotaviral diarrhea. As most of the diarrheas in children are viral in etiology and self-limiting in nature, we feel that unnecessary antibiotics are not only irrational but also unscientific. The effectiveness of nitazoxanide in viral diarrhea, if any, should be analyzed thoroughly by reviewing the available results from large, well designed and multicentric RCTs in developing countries before drawing any ambiguous conclusions. In view of high disease burden in developing countries, plots to exploit the situation by pharma majors to their economic benefit should be condemned strictly. Evidence based precise guidelines for the use of antibiotics in acute watery diarrhea especially for developing countries should be adopted before prescribing drugs pushed by pharmaceutical companies.

Sequential Use of Nitazoxanide (NTZ) as a Salvage Therapy in Patient with Recurrent Mild to Moderate Clostridium Difficile Infection (CDI): A Prospective, Open-label, Randomized Clinical Trial

Purpose: Vancomycin and metronidazole are currently the recommended therapies for CDI. Treatment failure is due to increasing antimicrobial resistance, insufficient length of therapy, and suboptimal drug exposure. Recurrence is estimated up to 20-50% in susceptible populations. We utilize a novel sequential nitazoxanide treatment for 28 days for recurrent CDI. Methods: Thirty (n=30) patients (age: 57.9±8.1 years; 13 non-hospital and 17 hospital acquired) were treated with oral vancomycin or metronidazole for 14 days and had recurrent CDI within 60 days posttreatment. All patients had abdominal pain, fever, diarrhea >3 times/day, leukocytes >12,000, and positive stool toxin assay with Elisa A/B. All were randomized into two groups: Group A (n=15) patients received nitazoxanide 500 mg BID for 14 days, followed by 250 mg BID for 7 days, followed by 125 mg BID for 7 days; Group (n=15) received vancomycin 250 mg QID for 14 days, followed by 250 mg BID for 7 days, followed by 125 mg BID for 7 days. Exclusion criteria: sepsis, toxic megacolon, inflammatory bowel disease, celiac disease, other colitidies, renal sufficiency, probiotic use, immunocompromised state, hemodialysis, or recent chemotherapy. Results: Stool assay PCR for CDI was negative in 10/15 (66.7%) patients after sequential nitazoxanide treatment and in 11/15 (73.3%) patients with sequential vancomycin therapy. There was no significant difference (p=0.99, Fisher's exact test) in fecal eradication rate of CDI between the two treatment groups. Side effects with nitazoxanide treatment were minimal including nausea (n=3), vomiting (n=1), constipation (n=4), bloating (n=2), loss of appetite (n=5), and yellow skin color (n=3). This was comparable to vancomycin. Conclusion: This novel sequential therapy with nitazoxanide shows a comparable cure rate to sequential oral vancomycin treatment for recurrent CDI. Nitazoxanide has an advantageous cost benefit over oral vancomycin with minimal side effects. A larger, double-blinded clinical trial is warranted for validation.

OL-010 Sequential use of nitazoxanide (NTZ) as a salvage therapy in patient with recurrent mild to moderate Clostridium difficile infection (CDI): a prospective, open-label, randomized clinical trial

OL-010 Sequential use of nitazoxanide (NTZ) as a salvage therapy in patient with recurrent mild to moderate Clostridium difficile infection (CDI): a prospective, open-label, randomized clinical trial

Prophylactic and therapeutic efficacy of nitazoxanide against Cryptosporidium parvum in experimentally challenged neonatal calves

Diarrhoea caused by Cryptosporidium parvum is a major problem in calves younger than 4 weeks of age. To date only a few compounds have been approved for prophylactic and none for therapeutic use. Nitazoxanide (NTZ) has proven its efficacy in vitro against C. parvum and is approved by FDA for the treatment of human cryptosporidiosis. In a first experimental study, 3 uninfected calves were treated with NTZ and pharmacokinetics was followed through blood samples. Serum samples of uninfected treated calves contained both NTZ metabolites (tizoxanide and tizoxanide glucuronide) and oral administration at 12 h intervals was considered as optimal. Three groups of three calves (1–3 days old) were then each inoculated with 1 × 10 7 oocysts of C. parvum (cattle genotype): the prophylactic group received 15 mg/kg body weight NTZ twice daily orally in milk from 1 day before to 8 days postinoculation (dpi). The therapeutic group received the same dosage of NTZ for 10 days from the appearance of diarrhoea (between 1 and 5 dpi). The control group was left untreated. All calves were monitored daily from day −1 to 28 dpi and faecal samples were collected for evaluation of consistency and for determination of oocyst numbers per gram (OPG) of faeces. Diarrhoea was observed in all calves within the first week. Neither prophylactic nor therapeutic use of NTZ improved the clinical appearance and calves of the therapeutic showed a longer diarrheic episode ( p < 0.05) with strong altered faecal consistence compared to the untreated control group. The number of days with oocyst excretion did not differ significantly between the groups. In 5 out of 6 infected and treated calves oocyst excretion stopped only after discontinuation of treatment. In the prophylactic and in the control group mean values of the sum of the daily OPG per calf (8.5 × 10 6 and 8.0 × 10 6, respectively) and of the mean daily number of OPG (0.3 × 10 6 and 0.3 × 10 6, respectively) were similar, while the therapeutic group showed significantly lower values (1.9 × 10 6 and 0.06 × 10 6, respectively, p < 0.05). However oocyst determinations in this group may have been altered by the severe diarrhoea, diluting oocyst densities in the analysed faecal samples. In conclusion, these preliminary results about the first prophylactic and therapeutic use of NTZ in calves did not show the expected positive effect on the course of the Cryptosporidium-infection, neither on reducing the clinical severity, nor on oocyst excretion.