Rifabutin: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Rifabutin}} | {{Rifabutin}} | ||
{{CMG}} ; | {{CMG}}; {{AE}} {{chetan}} | ||
==Overview== | ==Overview== | ||
Rifabutin (Rfb) is a [[bactericidal]] [[antibiotic]] drug primarily used in the treatment of [[tuberculosis]]. The drug is a semi-synthetic derivative of [[rifamycin]] S. Its effect is based on blocking the DNA-dependent RNA-polymerase of the bacteria. It is effective against [[Gram-positive]] and some [[Gram-negative]] bacteria, but also against the highly resistant [[Mycobacteria]], e.g. ''[[Mycobacterium tuberculosis]]'', ''[[Mycobacterium leprae|M. leprae]]'', and ''[[Mycobacterium avium intracellulare|M. avium intracellulare]]''. | |||
==Category== | ==Category== | ||
Antimycobacterial | Antimycobacterial | ||
==US Brand Names== | ==US Brand Names== | ||
MYCOBUTIN® | |||
==FDA Package Insert== | ==FDA Package Insert== | ||
'''[[Rifabutin description|Description]]''' | |||
''' [[Rifabutin description|Description]]''' | |||
'''| [[Rifabutin clinical pharmacology|Clinical Pharmacology]]''' | '''| [[Rifabutin clinical pharmacology|Clinical Pharmacology]]''' | ||
'''| [[Rifabutin microbiology|Microbiology]]''' | '''| [[Rifabutin microbiology|Microbiology]]''' | ||
| Line 27: | Line 30: | ||
==Mechanisms of Action== | ==Mechanisms of Action== | ||
The antibacterial activity of rifamycins relies on the inhibition of bacterial DNA-dependent RNA synthesis.<ref>{{cite journal |author=Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. |journal=Nature |title=Effect of rifamycin on protein synthesis |volume=207 |pages=417–8 |year=1965 |doi=10.1038/207417a0 |pmid=4957347 |issue=995}}</ref> This is due to the high affinity of rifamycins to prokaryotic [[RNA polymerase]]. Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide ("steric-occlusion" mechanism).<ref name="Campbell">{{cite journal|author=Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A.|year=2001|title=Structural mechanism for rifampicin inhibition of bacterial RNA polymerase|journal=Cell|volume=104|issue=6|pages=901–12|PMID=11290327|doi=10.1016/S0092-8674(01)00286-0}}</ref><ref name="Feklistov">{{cite journal|author=Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., [[Richard H. Ebright|Ebright, R.H.]]|year=2008|title=Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center|journal=Proc Natl Acad Sci USA|volume=105|issue=39|pages=14820–5|PMID=18787125|doi=10.1073/pnas.0802822105}}</ref> If rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosynthesis, consistent with a steric-occlusion mechanism. | The antibacterial activity of rifamycins relies on the inhibition of bacterial DNA-dependent RNA synthesis.<ref>{{cite journal |author=Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. |journal=Nature |title=Effect of rifamycin on protein synthesis |volume=207 |pages=417–8 |year=1965 |doi=10.1038/207417a0 |pmid=4957347 |issue=995}}</ref> This is due to the high affinity of rifamycins to prokaryotic [[RNA polymerase]]. Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide ("steric-occlusion" mechanism).<ref name="Campbell">{{cite journal|author=Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A.|year=2001|title=Structural mechanism for rifampicin inhibition of bacterial RNA polymerase|journal=Cell|volume=104|issue=6|pages=901–12|PMID=11290327|doi=10.1016/S0092-8674(01)00286-0}}</ref><ref name="Feklistov">{{cite journal|author=Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., [[Richard H. Ebright|Ebright, R.H.]]|year=2008|title=Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center|journal=Proc Natl Acad Sci USA|volume=105|issue=39|pages=14820–5|PMID=18787125|doi=10.1073/pnas.0802822105}}</ref> If rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosynthesis, consistent with a steric-occlusion mechanism. | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Antibiotics]] | [[Category:Antibiotics]] | ||
[[Category:Wikinfect]] | [[Category:Wikinfect]] | ||
Revision as of 03:04, 4 January 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Overview
Rifabutin (Rfb) is a bactericidal antibiotic drug primarily used in the treatment of tuberculosis. The drug is a semi-synthetic derivative of rifamycin S. Its effect is based on blocking the DNA-dependent RNA-polymerase of the bacteria. It is effective against Gram-positive and some Gram-negative bacteria, but also against the highly resistant Mycobacteria, e.g. Mycobacterium tuberculosis, M. leprae, and M. avium intracellulare.
Category
Antimycobacterial
US Brand Names
MYCOBUTIN®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Overdosage | Dosage and Administration | How Supplied | Labels and Packages
Mechanisms of Action
The antibacterial activity of rifamycins relies on the inhibition of bacterial DNA-dependent RNA synthesis.[1] This is due to the high affinity of rifamycins to prokaryotic RNA polymerase. Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide ("steric-occlusion" mechanism).[2][3] If rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosynthesis, consistent with a steric-occlusion mechanism.
References
- ↑ Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. (1965). "Effect of rifamycin on protein synthesis". Nature. 207 (995): 417–8. doi:10.1038/207417a0. PMID 4957347.
- ↑ Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell. 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.
- ↑ Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA. 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMID 18787125.