zithromax and nitazoxanide

Topics: AIDS-Related Opportunistic Infections; Animals; Antiretroviral Therapy, Highly Active; Azithromycin; Biliary Tract Diseases; Coccidiostats; Cryptosporidiosis; Humans; Immunocompromised Host; Nitro Compounds; Paromomycin; Rifamycins; Rifaximin; Thiazoles

Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.. We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.. In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.. ClinicalTrials.gov NCT03268902.

Topics: Adult; Anti-Infective Agents; Azithromycin; Child Development; Double-Blind Method; Drug Administration Schedule; Female; Growth Disorders; Humans; Infant; Infant, Newborn; Intestinal Diseases, Parasitic; Niacinamide; Nitro Compounds; Pregnancy; Tanzania; Thiazoles

Micronutrient deficiencies and enteric infections negatively impact child growth and development. We enrolled children shortly after birth in a randomized, placebo-controlled, 2 × 2 factorial interventional trial in Haydom, Tanzania, to assess nicotinamide and/or antimicrobials (azithromycin and nitazoxanide) effect on length at 18 months of age. Cognitive score at 18 months using the Malawi Developmental Assessment Tool (MDAT), which includes gross motor, fine motor, language, and social assessments, was a secondary outcome. Here, we present the MDAT results of 1,032 children. There was no effect of nicotinamide (change in development-for-age Z score [DAZ] -0.08; 95% CI: -0.16, 0) or antimicrobials (change in DAZ 0.04; 95% CI: -0.06, 0.13) on overall MDAT score. The interventions had no effect on cognitive outcomes in subgroups defined by gender, socioeconomic status, birthweight, and birth season or on MDAT subscores. Further analyses are needed to identify targetable risk factors for impaired cognitive development in these settings.

Topics: Anti-Infective Agents; Antiparasitic Agents; Azithromycin; Child Development; Cognitive Aging; Cohort Studies; Early Intervention, Educational; Female; Humans; Infant; Male; Niacinamide; Nitro Compounds; Seasons; Tanzania; Thiazoles; Vitamin B Complex

Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan-kynurenine-niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant's birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (-0.54 difference in weight-for-age

Topics: Adult; Azithromycin; Body Weight; Child Health; Child Nutrition Disorders; Child, Preschool; Cohort Studies; Early Medical Intervention; Female; Humans; Infant; Infant, Newborn; Male; Mothers; Neonatal Sepsis; Niacinamide; Nitro Compounds; Poverty; Respiratory Tract Infections; Rural Population; Seasons; Surveys and Questionnaires; Tanzania; Thiazoles; Young Adult

In many developing areas in the world, a high burden of enteric pathogens in early childhood are associated with growth deficits. The tryptophan-kynurenine-niacin pathway has been linked to enteric inflammatory responses to intestinal infections. However, it is not known in these settings whether scheduled antimicrobial intervention to reduce subclinical enteric pathogen carriage or repletion of the tryptophan-kynurenine-niacin pathway improves linear growth and development.. We are conducting a randomised, placebo-controlled, factorial intervention trial in the rural setting of Haydom, Tanzania. We are recruiting 1188 children within the first 14 days of life, who will be randomised in a 2×2 factorial design to administration of antimicrobials (azithromycin and nitazoxanide, randomised together) and nicotinamide. The nicotinamide is administered as a daily oral dose, which for breast-feeding children aged 0-6 months is given to the mother and for children aged 6-18 months is given to the child directly. Azithromycin is given to the child as a single oral dose at months 6, 9, 12 and 15; nitazoxanide is given as a 3-day course at months 12 and 15. Mother/child pairs are followed via monthly in-home visits. The primary outcome is the child's length-for-age Z-score at 18 months. Secondary outcomes for the child include additional anthropometry measures; stool pathogen burden and bacterial microbiome; systemic and enteric inflammation; blood metabolomics, growth factors, inflammation and nutrition; hydrogen breath assessment to estimate small-intestinal bacterial overgrowth and assessment of cognitive development. Secondary outcomes for the mother include breastmilk content of nicotinamide, other vitamins and amino acids; blood measures of tryptophan-kynurenine-niacin pathway and stool pathogens.. This trial has been approved by the Tanzanian National Institute for Medical Research, the Tanzanian FDA and the University of Virginia IRB. Findings will be presented at national and international conferences and published in peer-review journals.. 5.0, 4 December 2017.. Haydom Lutheran Hospital, Haydom, Manyara, Tanzania.. NCT03268902; Pre-results.

Topics: Administration, Oral; Anti-Bacterial Agents; Antiparasitic Agents; Azithromycin; Breast Feeding; Double-Blind Method; Female; Growth and Development; Humans; Infant; Infant, Newborn; Male; Mothers; Niacinamide; Nitro Compounds; Randomized Controlled Trials as Topic; Tanzania; Thiazoles; Vitamin B Complex

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.

Topics: Azithromycin; COVID-19; Humans; Mexico; Outpatients; Prednisone; SARS-CoV-2; Treatment Outcome

Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach.. We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19.. Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Repositioning; Humans; Interferons; Interleukin-6; Nitro Compounds; Observational Studies as Topic; SARS-CoV-2; Thiazoles

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately widely ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical COVID-19 cases.

Topics: Antiparasitic Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Humans; Nitro Compounds; Pandemics; Pneumonia, Viral; SARS-CoV-2; Thiazoles

Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Antiparasitic Agents; Azithromycin; Cryptosporidiosis; Cryptosporidium; Disease Models, Animal; Drug Therapy, Combination; Nitro Compounds; Sus scrofa; Swine; Thiazoles; Treatment Outcome

Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Topics: Adult; Animals; Azithromycin; Cryptosporidiosis; Cryptosporidium parvum; Diagnosis, Differential; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Lymphopenia; Male; Middle Aged; Nitro Compounds; Thiazoles; Transplantation, Homologous; Young Adult

Cryptosporidium species and Giardia intestinalis are the most common enteric protozoan pathogens affecting humans worldwide. In recent years, nitazoxanide has been licensed in the United States for the treatment of cryptosporidiosis in non-immunodeficient children and adults, becoming the first drug approved for treating this disease. There is a need for a highly effective treatment for cryptosporidiosis in immunodeficient patients, but the quest for such a drug has proven to be elusive. While not effective against Cryptosporidium, nitroimidazoles such as metronidazole or tinidazole are effective treatments for giardiasis and can be administered as a single dose. Albendazole and nitazoxanide are effective against giardiasis but require multiple doses. Nitazoxanide is the first new drug developed for treating giardiasis in more than 20years. New potentially promising drug targets in Cryptosporidium and Giardia have been identified, but there appears to be little activity toward clinical development of new drugs.

Topics: AIDS-Related Opportunistic Infections; Antibodies, Monoclonal; Antiparasitic Agents; Antiretroviral Therapy, Highly Active; Azithromycin; Benzimidazoles; Cryptosporidiosis; Giardia lamblia; Giardiasis; Humans; Nitro Compounds; Nitroimidazoles; Paromomycin; Roxithromycin; Thiazoles

The in vitro activity of nitazoxanide alone and in combination with azithromycin and rifabutin was investigated against four clinical isolates of Cryptosporidium parvum. The susceptibility tests were performed by inoculation of the isolates on toe cell monolayers and determination of the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of each agent. Antibiotic-free plates were used as controls. Experiments were performed in triplicate. Nitazoxanide showed moderate anticryptosporidial activity: it suppressed the growth of parasites by >50% at 8 mg/L. A parasite reduction of 79.8-83.9% was observed when nitazoxanide 8 mg/L was combined with azithromycin 8 mg/L and rifabutin 8 mg/L. The study suggests that nitazoxanide may be active in inhibiting C. parvum growth in vitro upon combination with azithromycin or rifabutin.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cell Survival; Cells, Cultured; Cryptosporidiosis; Cryptosporidium parvum; Humans; Nitro Compounds; Rifabutin; Thiazoles

A 24-year-old HIV-positive heterosexual woman with disseminated cryptosporidiosis was monitored from January 1998 to May 1999. During this period, consecutive stool, sputum, and bile examinations showed the constant presence of Cryptosporidium oocysts. Although the patient was repeatedly treated with oral paromomycin and azithromycin and, finally, nitazoxanide, her condition continued to deteriorate. In order to monitor the in vitro susceptibility of the parasite, specimens from various sites were collected periodically. When the first clinical isolate was tested, the antimicrobial agents used (azithromycin at a concentration of 8 mg/l, paromomycin at of 1 mg/ml, and nitazoxanide at 10 mg/l) produced a decrease in parasite counts of 26.5%, 63.4%, and 67.2%, respectively. Subsequent isolates of Cryptosporidium parvum showed similar susceptibilities. This case demonstrates that failure of clinical treatment corresponded to inadequate growth inhibition of the parasite in vitro.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Antiprotozoal Agents; Azithromycin; Cryptosporidiosis; Cryptosporidium; Drug Therapy, Combination; Feces; Female; Humans; Nitro Compounds; Paromomycin; Thiazoles; Treatment Outcome