1. Antimicrobial treatment with the fixed-dose antibiotic combination RHB-104 for Mycobacterium avium subspecies paratuberculosis in Crohn’s disease: pharmacological and clinical implications
- Author
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Greta Lorenzon, Santino Marchi, Francesco Costa, Linda Ceccarelli, Andrea Buda, Elisa Marabotto, Vincenzo Savarino, Nicola de Bortoli, Giorgia Bodini, Corrado Blandizzi, Fabiana Zingone, Edoardo Savarino, Sonia Facchin, and Lorenzo Bertani
- Subjects
Crohn’s disease ,0301 basic medicine ,Rifabutin ,clarithromycin ,clofazimine ,fixed drug combination ,inflammatory bowel disease ,Mycobacterium avium paracellulare ,RHB-104 ,rifabutin ,Pharmacology ,Drug Discovery3003 Pharmaceutical Science ,Clinical Biochemistry ,medicine.drug_class ,Antibiotics ,Disease ,Clofazimine ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Clarithromycin ,Paratuberculosis ,Drug Discovery ,medicine ,Animals ,Humans ,Crohn's disease ,biology ,business.industry ,Remission Induction ,biology.organism_classification ,medicine.disease ,Mycobacterium avium subspecies paratuberculosis ,digestive system diseases ,Anti-Bacterial Agents ,Mycobacterium avium subsp. paratuberculosis ,Drug Combinations ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,business ,medicine.drug - Abstract
Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology. However, increasing evidence suggests Mycobacterium avium subspecies paratuberculosis (MAP) as a putative causative agent: 1) MAP is the etiological agent of Johne's disease, a granulomatous enteritis affecting ruminants, which shares clinical and pathological features with CD; 2) MAP has been detected in tissues and blood samples from CD patients; 3) case reports have documented a favorable therapeutic response to anti-MAP antibiotics. Area covered: This review provides an appraisal of current information on MAP characteristics, diagnostic methodologies and emerging drug treatments. The authors focus on RHB-104, a novel oral formulation containing a fixed-dose combination of clarithromycin, clofazimine and rifabutin, endowed with synergistic inhibitory activity on MAP strains isolated from CD patients. Expert opinion: Based on encouraging in vitro data, RHB-104 has entered recently the clinical phase of its development, and is being investigated in a randomized, placebo-controlled phase III trial aimed at evaluating its efficacy and safety in CD. Provided that the overall clinical development will support the suitability of RHB-104 for inducing disease remission in CD patients with documented MAP infection, this novel antibiotic combination will likely take a relevant position in the therapeutic armamentarium for CD management.
- Published
- 2019
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