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A Clofazimine-Containing Regimen Confers Improved Treatment Outcomes in Macrophages and in a Murine Model of Chronic Progressive Pulmonary Infection Caused by the Mycobacterium avium Complex

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dc.contributor.author김이한-
dc.contributor.author신성재-
dc.date.accessioned2021-04-29T17:11:30Z-
dc.date.available2021-04-29T17:11:30Z-
dc.date.issued2021-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/182224-
dc.description.abstractTreatment outcomes using the standard regimen (a macrolide, ethambutol, and rifampicin) for Mycobacterium avium complex-pulmonary disease (MAC-PD) remain unsatisfactory. Thus, improved treatment regimens for MAC-PD are required. Clofazimine has recently been revisited as an effective drug against mycobacterial infection. We performed a comparison between the standard regimen and an alternative regimen (replacing the rifampicin of the standard regimen with clofazimine) based on the intracellular anti-MAC activities of the individual drugs in a murine model of chronic progressive MAC-pulmonary infection (MAC-PI). The intracellular anti-MAC activities of the individual drugs and their combinations in murine bone marrow-derived macrophages (BMDMs) were determined. The treatment efficacies of the standard and clofazimine-containing regimens were evaluated in mice chronically infected with M. avium by initiating 2- and 4-week treatment at 8 weeks post-infection. Bacterial loads in the lung, spleen, and liver were assessed along with lung inflammation. Insufficient intracellular anti-MAC activity of rifampicin in BMDMs was recorded despite its low in vitro minimum inhibitory concentrations (MICs), whereas optimal intracellular killing activity against all tested MAC strains was achieved with clofazimine. Compared to the standard regimen, the clofazimine-containing regimen significantly reduced CFUs in all organs and achieved marked reductions in lung inflammation. The replacement of rifampicin with clofazimine in the treatment regimen resulted in more favorable outcomes in an animal model of chronic progressive MAC-PI. Intriguingly, 2 weeks of treatment with the clofazimine-containing regimen reduced bacterial loads more effectively than 4 weeks of treatment with the standard regimen in M. avium-infected mice. Thus, the clofazimine-containing regimen also had a treatment-shortening effect.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherFrontiers Research Foundation-
dc.relation.isPartOfFRONTIERS IN MICROBIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleA Clofazimine-Containing Regimen Confers Improved Treatment Outcomes in Macrophages and in a Murine Model of Chronic Progressive Pulmonary Infection Caused by the Mycobacterium avium Complex-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentResearch Institute (부설연구소)-
dc.contributor.googleauthorJu Mi Lee-
dc.contributor.googleauthorJiyun Park-
dc.contributor.googleauthorSangwon Choi-
dc.contributor.googleauthorByung Woo Jhun-
dc.contributor.googleauthorSu-Young Kim-
dc.contributor.googleauthorKyung-Wook Jo-
dc.contributor.googleauthorJung Joo Hong-
dc.contributor.googleauthorLee-Han Kim-
dc.contributor.googleauthorSung Jae Shin-
dc.identifier.doi10.3389/fmicb.2020.626216-
dc.contributor.localIdA06045-
dc.contributor.localIdA02114-
dc.relation.journalcodeJ03413-
dc.identifier.eissn1664-302X-
dc.identifier.pmid33519787-
dc.subject.keywordMycobacterium avium complex-pulmonary disease-
dc.subject.keywordchronic progressive murine model-
dc.subject.keywordclofazimine-
dc.subject.keywordclofazimine-containing regimen-
dc.subject.keywordin vivo drug susceptibility test-
dc.subject.keywordintracellular drug susceptibility test-
dc.subject.keywordminimum inhibitory concentrations-
dc.subject.keywordstandard treatment regimen-
dc.contributor.alternativeNameKim, Lee-Han-
dc.contributor.affiliatedAuthor김이한-
dc.contributor.affiliatedAuthor신성재-
dc.citation.volume11-
dc.citation.startPage626216-
dc.identifier.bibliographicCitationFRONTIERS IN MICROBIOLOGY, Vol.11 : 626216, 2021-01-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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