Rifampin in the Treatment of Leprosy

Bullock, Ward E.

doi:10.1093/clinids/5.supplement_3.s606

Cited by 19 publications

(16 citation statements)

References 18 publications

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“…Dapsone has been used in the treatment of leprosy since 1945 [Zhu and Stiller, ]. Due to the emergence and spread of dapsone‐resistant M. leprae from 1976 [Friedmann, ], WHO recommended and implemented control measure for leprosy with MDT, with the inclusion of rifampin in 1985 [Bullock, ] and ofloxacin in 1996 as a second line antibiotic [Ji and Grosset, ]. In India, the prevalence rate for leprosy before the initiation of MDT was 24/10,000 population.…”

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confidence: 99%

Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy

Chaitanya

Das

Bhat

et al. 2015

J of Cellular Biochemistry

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The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy.

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confidence: 99%

Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy

Chaitanya

Das

Bhat

et al. 2015

J of Cellular Biochemistry

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“…2,3 Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells by binding its beta-subunit, thereby preventing transcription to RNA and subsequent translation to proteins. 4,5 Gastrointestinal problems (nausea, vomiting, diarrhea, and abdominal pain), hepatotoxicity, drug eruption, flu syndrome, hemolytic anemia, and renal failure are common side effects of rifampicin, particularly during intermittent treatment, but thrombocytopenia is rare. 3,5,6 In this report, the patient received anti-leprosy treatment including rifampicin for the first two rounds.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Gastrointestinal problems (nausea, vomiting, diarrhea, and abdominal pain), hepatotoxicity, drug eruption, flu syndrome, hemolytic anemia, and renal failure are common side effects of rifampicin, particularly during intermittent treatment, but thrombocytopenia is rare. 3,5,6 In this report, the patient received anti-leprosy treatment including rifampicin for the first two rounds. Both times, the patient developed thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Rifampicin-Induced Thrombocytopenia in a Patient with Borderline Lepromatous Leprosy

Shui

Shi

Jing

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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“…It is rapidly bactericidal against M. leprae with bacteriologic success within 3 weeks of starting therapy. Even a single high dose was efficacious in a mouse footpad model . The rifamycins bind to the β‐subunit of RNA polymerase in prokaryotic cells and block RNA transcription.…”

Section: Treatment Of the Diseasementioning

confidence: 99%

“…Even a single high dose was efficacious in a mouse footpad model. 45 The rifamycins bind to the b-subunit of RNA polymerase in prokaryotic cells and block RNA transcription. Bactericidal activity is observed even in slowly dividing cells, such as Mycobacterium species.…”

Section: Rifampinmentioning

confidence: 99%

Hansen's Disease (Leprosy): Current and Future Pharmacotherapy and Treatment of Disease‐Related Immunologic Reactions

Legendre¹,

Muzny

Swiatlo

2012

Pharmacotherapy

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Hansen's disease, also known as leprosy, remains an important public health problem throughout the world, including North America. The causative microbe in Hansen's disease is Mycobacterium leprae, an acid-fast organism that is difficult to grow in vitro. The nine-banded armadillo is the major animal reservoir in the United States. Manifestations of disease vary based on host immune response and can range from tuberculoid to lepromatous leprosy (paucibacillary to multibacillary disease). Hansen's disease typically affects the skin, nerves, and eyes, and patients may present with skin lesions, weakness, numbness, eye pain, or loss of vision. Definitive diagnosis is based on a combination of physical examination findings and skin biopsy and/or smear. Modern antibacterial therapy typically consists of combinations of dapsone and rifampin with or without clofazimine. Clofazimine is available only as an investigational drug through the National Hansen's Disease Program. Other options include moxifloxacin, ofloxacin, minocycline, and clarithromycin. Hansen's disease is associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions, during which the disease process appears to worsen dramatically. These reactions may occur at any time before, during, or after treatment. Antibacterial therapy should usually be continued during these reactions. Treatment options for these reactions differ based on clinical manifestations and include corticosteroids, thalidomide, pentoxiphylline, tumor necrosis factor inhibitors, and T cell inhibitors. Prompt diagnosis, antimicrobial therapy, and treatment of reactions dramatically reduce complications of the disease.

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Rifampin in the Treatment of Leprosy

Cited by 19 publications

References 18 publications

Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy

Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy

Case Report: Rifampicin-Induced Thrombocytopenia in a Patient with Borderline Lepromatous Leprosy

Hansen's Disease (Leprosy): Current and Future Pharmacotherapy and Treatment of Disease‐Related Immunologic Reactions

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