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The association between sterilizing activity and drug distribution into tuberculosis lesions

DC FieldValueLanguage
dc.contributor.author조상래-
dc.date.accessioned2016-02-04T11:54:19Z-
dc.date.available2016-02-04T11:54:19Z-
dc.date.issued2015-
dc.identifier.issn1078-8956-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141459-
dc.description.abstractFinding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside. In contrast, moxifloxacin, which is active in vitro against a subpopulation of Mycobacterium tuberculosis that persists in specific niches under drug pressure and has achieved treatment shortening in mice, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug-resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration may contribute to treatment outcome has wide implications for TB.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1223~1227-
dc.relation.isPartOfNATURE MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAntitubercular Agents/pharmacokinetics-
dc.subject.MESHAntitubercular Agents/pharmacology*-
dc.subject.MESHAntitubercular Agents/therapeutic use-
dc.subject.MESHHumans-
dc.subject.MESHMycobacterium tuberculosis/drug effects-
dc.subject.MESHPyrazinamide/pharmacokinetics-
dc.subject.MESHPyrazinamide/pharmacology*-
dc.subject.MESHPyrazinamide/therapeutic use-
dc.subject.MESHRifampin/pharmacokinetics-
dc.subject.MESHRifampin/pharmacology*-
dc.subject.MESHRifampin/therapeutic use-
dc.subject.MESHTuberculosis/drug therapy*-
dc.subject.MESHTuberculosis/metabolism-
dc.titleThe association between sterilizing activity and drug distribution into tuberculosis lesions-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학)-
dc.contributor.googleauthorBrendan Prideaux-
dc.contributor.googleauthorLaura E Via-
dc.contributor.googleauthorMatthew D Zimmerman-
dc.contributor.googleauthorSeokyong Eum-
dc.contributor.googleauthorJansy Sarathy-
dc.contributor.googleauthorPaul O'Brien-
dc.contributor.googleauthorChao Chen-
dc.contributor.googleauthorFirat Kaya-
dc.contributor.googleauthorDanielle M Weiner-
dc.contributor.googleauthorPei-Yu Chen-
dc.contributor.googleauthorTaeksun Song-
dc.contributor.googleauthorMyungsun Lee-
dc.contributor.googleauthorTae Sun Shim-
dc.contributor.googleauthorJeong Su Cho-
dc.contributor.googleauthorWooshik Kim-
dc.contributor.googleauthorSang Nae Cho-
dc.contributor.googleauthorKenneth N Olivier-
dc.contributor.googleauthorClifton E Barry III-
dc.contributor.googleauthorVéronique Dartois-
dc.identifier.doi10.1038/nm.3937-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03824-
dc.relation.journalcodeJ02296-
dc.identifier.eissn1546-170X-
dc.identifier.pmid26343800-
dc.identifier.urlhttp://www.nature.com/nm/journal/v21/n10/full/nm.3937.html-
dc.contributor.alternativeNameCho, Sang Nae-
dc.contributor.affiliatedAuthorCho, Sang Nae-
dc.rights.accessRightsnot free-
dc.citation.volume21-
dc.citation.number10-
dc.citation.startPage1223-
dc.citation.endPage1227-
dc.identifier.bibliographicCitationNATURE MEDICINE, Vol.21(10) : 1223-1227, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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