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A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis
BACKGROUND: Most recently we reported that RHB‑104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041445/ https://www.ncbi.nlm.nih.gov/pubmed/27708718 http://dx.doi.org/10.1186/s13099-016-0127-z |
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author | Qasem, Ahmad Safavikhasraghi, Mitra Naser, Saleh A. |
author_facet | Qasem, Ahmad Safavikhasraghi, Mitra Naser, Saleh A. |
author_sort | Qasem, Ahmad |
collection | PubMed |
description | BACKGROUND: Most recently we reported that RHB‑104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination exhibited unique synergistic antimicrobial growth activity. The proprietary RHB-104 capsule formulation contains active ingredients (63.3 % Clarithromycin (CLA), 6.7 % Clofazimine (CLO) and 30 % Rifabutin (RIF)). In our earlier study, we could not dissolve the proprietary RHB-104 capsule formulation in one compatible solvent. Consequently, we re-created RHB-104 analog by adding appropriate concentrations of each of the three antibiotics into the cultures. The Minimum inhibitory concentration (MIC) for RHB-104 analog, CLA, CLO, RIF, CLA-CLO, CLA-RIF, CLO-RIF and their individual solvents were reported earlier (Alcedo et al. in Gut Pathog 14:32, 2016). In this study, we succeeded in dissolving the proprietary RHB-104 capsule formulation in a single proprietary solvent. This study is designed to compare of the MIC the proprietary RHB-104 capsule formulation to RHB-104 analog against MAP and other microorganisms. METHODS: BD Bactec™ MGIT™ Para-TB medium (Sparks, MD) system was used to determine the MIC of the proprietary RHB-104 capsule formulation and RHB-104 analog and their solvents against MAP and several other microorganisms. The final concentration of solvents used to dissolve all the drugs were ≤0.5 % (v/v). RESULTS: The MIC for the RHB-104 proprietary solvent against MAP was consistent against all microorganisms tested in the study at 12.5 % (v/v). The MIC for the proprietary RHB-104 capsule formulation was similar to RHB-104 analog against several MAP clinical strains with MIC ≤ 0.2 μg/mL. The MIC for the proprietary RHB-104 capsule formulation was at 2.0 μg/mL against MAP strain MS 137 and M. avium strain JF7 compared to 4.0 ug/mL for RHB-104 analog. Similarly, the MIC of RHB-104 formulation capsule was significantly lower than RHB-104 analog against M. tuberculosis HR237, M. fortuitism subspecies fortuitum, M. smegmatis ATCC 27199, Staphylococcus aureus ATCC 25923 and Listeria monocytogenes ATCC 19112. CONCLUSION: The data demonstrated that the proprietary RHB-104 capsule formulation is more potent in culture against Mycobacteria and other microorganisms especially those with MIC >0.2. Formulation of multi-drugs in a single capsule results in potent synergistic anti-microbial activity far exceeds treatment the culture with multi-individually dissolved drugs. RHB-104 capsule formulation should be more effective to eradicate MAP infection in patients with CD. The study provides evidence that combining weak antibiotics in one formulation might be the new silver bullet to combat bacteria. |
format | Online Article Text |
id | pubmed-5041445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50414452016-10-05 A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis Qasem, Ahmad Safavikhasraghi, Mitra Naser, Saleh A. Gut Pathog Letter to the Editor BACKGROUND: Most recently we reported that RHB‑104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination exhibited unique synergistic antimicrobial growth activity. The proprietary RHB-104 capsule formulation contains active ingredients (63.3 % Clarithromycin (CLA), 6.7 % Clofazimine (CLO) and 30 % Rifabutin (RIF)). In our earlier study, we could not dissolve the proprietary RHB-104 capsule formulation in one compatible solvent. Consequently, we re-created RHB-104 analog by adding appropriate concentrations of each of the three antibiotics into the cultures. The Minimum inhibitory concentration (MIC) for RHB-104 analog, CLA, CLO, RIF, CLA-CLO, CLA-RIF, CLO-RIF and their individual solvents were reported earlier (Alcedo et al. in Gut Pathog 14:32, 2016). In this study, we succeeded in dissolving the proprietary RHB-104 capsule formulation in a single proprietary solvent. This study is designed to compare of the MIC the proprietary RHB-104 capsule formulation to RHB-104 analog against MAP and other microorganisms. METHODS: BD Bactec™ MGIT™ Para-TB medium (Sparks, MD) system was used to determine the MIC of the proprietary RHB-104 capsule formulation and RHB-104 analog and their solvents against MAP and several other microorganisms. The final concentration of solvents used to dissolve all the drugs were ≤0.5 % (v/v). RESULTS: The MIC for the RHB-104 proprietary solvent against MAP was consistent against all microorganisms tested in the study at 12.5 % (v/v). The MIC for the proprietary RHB-104 capsule formulation was similar to RHB-104 analog against several MAP clinical strains with MIC ≤ 0.2 μg/mL. The MIC for the proprietary RHB-104 capsule formulation was at 2.0 μg/mL against MAP strain MS 137 and M. avium strain JF7 compared to 4.0 ug/mL for RHB-104 analog. Similarly, the MIC of RHB-104 formulation capsule was significantly lower than RHB-104 analog against M. tuberculosis HR237, M. fortuitism subspecies fortuitum, M. smegmatis ATCC 27199, Staphylococcus aureus ATCC 25923 and Listeria monocytogenes ATCC 19112. CONCLUSION: The data demonstrated that the proprietary RHB-104 capsule formulation is more potent in culture against Mycobacteria and other microorganisms especially those with MIC >0.2. Formulation of multi-drugs in a single capsule results in potent synergistic anti-microbial activity far exceeds treatment the culture with multi-individually dissolved drugs. RHB-104 capsule formulation should be more effective to eradicate MAP infection in patients with CD. The study provides evidence that combining weak antibiotics in one formulation might be the new silver bullet to combat bacteria. BioMed Central 2016-09-29 /pmc/articles/PMC5041445/ /pubmed/27708718 http://dx.doi.org/10.1186/s13099-016-0127-z Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Letter to the Editor Qasem, Ahmad Safavikhasraghi, Mitra Naser, Saleh A. A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title | A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title_full | A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title_fullStr | A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title_full_unstemmed | A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title_short | A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis |
title_sort | single capsule formulation of rhb-104 demonstrates higher anti-microbial growth potency for effective treatment of crohn’s disease associated with mycobacterium avium subspecies paratuberculosis |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041445/ https://www.ncbi.nlm.nih.gov/pubmed/27708718 http://dx.doi.org/10.1186/s13099-016-0127-z |
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