RESUMEN
INTRODUCTION: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. METHODS AND ANALYSIS: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. ETHICS AND DISSEMINATION: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04305769.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Adolescente , Humanos , Ensayos Clínicos Fase II como Asunto , Infecciones por Clostridium/tratamiento farmacológico , Suplementos Dietéticos , Método Doble Ciego , Inflamación , Recurrencia Local de Neoplasia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , AdultoRESUMEN
Treatment of Mycobacterium avium disease remains challenging when macrolide resistance develops. We infected C57 beige mice and treated them with mefloquine, SRI-286, and moxifloxacin. SRI-286 (80 mg/kg) was bactericidal in the liver. Mefloquine plus moxifloxacin or mefloquine plus SRI-286 were better than mefloquine alone.
Asunto(s)
Antibacterianos/uso terapéutico , Compuestos Aza/uso terapéutico , Mefloquina/uso terapéutico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Quinolinas/uso terapéutico , Tioacetazona/análogos & derivados , Tioacetazona/uso terapéutico , Animales , Antibacterianos/efectos adversos , Compuestos Aza/efectos adversos , Recuento de Colonia Microbiana , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Fluoroquinolonas , Hígado/microbiología , Mefloquina/efectos adversos , Ratones , Ratones Endogámicos C57BL , Moxifloxacino , Infección por Mycobacterium avium-intracellulare/microbiología , Quinolinas/efectos adversos , Bazo/microbiología , Tioacetazona/efectos adversosRESUMEN
Macrolides are the core of effective drug regimens for the treatment of Mycobacterium avium complex (MAC) disease. Mefloquine (MFQ), moxifloxacin (MXF), and ethambutol (EMB), in combination, were evaluated against both clarithromycin-resistant (CLR-R) and CLR-susceptible (CLR-S) MAC; MFQ (40 mg/kg), MXF (100 mg/kg), or EMB (100 mg/kg/day) was given to mice for 4 weeks. MFQ was bactericidal, whereas MXF and EMB were bacteriostatic against both MAC 101 CLR-S and CLR-R. The combination of MFQ and EMB reduced (P<.05, for comparison with controls), and the combination of MFQ and MXF significantly reduced, the load of CLR-R in both the liver and the spleen. Treatment with all 3 drugs was associated with approximately 1-log reduction of CLR-R after 1 week, 2.1-log reduction of CLR-R after 4 weeks, and 2.17-log reduction in MAC/mL blood. Treatment of MAC 101 CLR-S strain had comparable results.