PMID- 33519787
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210202
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 11
DP  - 2020
TI  - 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.
PG  - 626216
LID - 10.3389/fmicb.2020.626216 [doi]
LID - 626216
AB  - Treatment 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.
CI  - Copyright (c) 2021 Lee, Park, Choi, Jhun, Kim, Jo, Hong, Kim and Shin.
FAU - Lee, Ju Mi
AU  - Lee JM
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Park, Jiyun
AU  - Park J
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Choi, Sangwon
AU  - Choi S
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Jhun, Byung Woo
AU  - Jhun BW
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung 
      Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
FAU - Kim, Su-Young
AU  - Kim SY
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung 
      Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
FAU - Jo, Kyung-Wook
AU  - Jo KW
AD  - Division of Pulmonology and Critical Care Medicine, Department of Internal 
      Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      South Korea.
FAU - Hong, Jung Joo
AU  - Hong JJ
AD  - National Primate Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Cheongju, South Korea.
FAU - Kim, Lee-Han
AU  - Kim LH
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Shin, Sung Jae
AU  - Shin SJ
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20210114
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC7841306
OTO - NOTNLM
OT  - Mycobacterium avium complex-pulmonary disease
OT  - chronic progressive murine model
OT  - clofazimine
OT  - clofazimine-containing regimen
OT  - in vivo drug susceptibility test
OT  - intracellular drug susceptibility test
OT  - minimum inhibitory concentrations
OT  - standard treatment regimen
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/02 06:00
MHDA- 2021/02/02 06:01
PMCR- 2021/01/14
CRDT- 2021/02/01 05:55
PHST- 2020/11/05 00:00 [received]
PHST- 2020/12/22 00:00 [accepted]
PHST- 2021/02/01 05:55 [entrez]
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/02/02 06:01 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - 10.3389/fmicb.2020.626216 [doi]
PST - epublish
SO  - Front Microbiol. 2021 Jan 14;11:626216. doi: 10.3389/fmicb.2020.626216. 
      eCollection 2020.