RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn's disease associated with Mycobacterium paratuberculosis. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Alcedo, Karel; Thanigachalam, Saisathya; Naser, Saleh
• Is Part Of: Gut pathogens. Volume 8:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Mycobacterium paratuberculosis -- Crohn's disease -- RHB-104 -- MIC -- Antibiotics -- IBD; Gastrointestinal system -- Microbiology -- Periodicals; 616.3
• DOI: 10.1186/s13099-016-0115-3
• Languages: English
• ISSNs: 1757-4749

Abstract

Abstract Background Mycobacterium avium subspeciesparatuberculosis (MAP) has been implicated as an etiological agent of Crohn's disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients. RHB-104, a drug formula with active ingredients composed of (63.3 %) CLA, (6.7 %) CLO, and (30 %) RIF, has been recently subjected to investigation in an FDA approved Phase III clinical trial to treat patients with moderate to severe CD. In this study, we determined the efficacy of RHB-104 active ingredients against MAP strains isolated from the blood, tissue, and milk of CD patients. Based on fluorescence quenching technology using the Bactec MGIT Para-TB medium, we determined the minimum inhibitory concentration (MIC) of CLA, CLO, RIF individually and in dual and triple combinations against 16 MAP clinical strains and 19 other mycobacteria. Results The MIC of all drugs against 35 different mycobacteria ranged between 0.25–20 μg/mL. However, the MIC of RHB-104 active ingredients regimen was the lowest at 0.25–10 μg/mL compared to the MIC of the other drugs at 0.5–20 μg/mL. The components of RHB-104 active ingredients at their individual concentrations or in dual combinations were not effective against all microorganisms compared to the triple combinations at MIC level. The MIC of CLA–CLO, CLA–RIF, and CLO–RIF regimens ranged between 0.5–1.25 μg/mL compared to 0.25 μg/mL of bactericidal effect of the triple combination. Conclusion The data clearly demonstrated that lower concentrations of the triple combination of RHB-104 active ingredients provided synergistic anti-MAP growth activity compared to individual or dual combinations of the drugs. Consequently, this is favorable and should lead to tolerable dosage that is desirable for long-term treatment of CD andMycobacterium avium complex disease.