PMID- 37996500
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231220
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Nov 23
TI  - Intracellular and in vivo activities of oxazolidinone drugs against Mycobacterium 
      avium complex infection.
PG  - 20631
LID - 10.1038/s41598-023-48001-y [doi]
LID - 20631
AB  - The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has 
      become a growing concern worldwide, and current treatments involving macrolides 
      (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited 
      success, highlighting the need for better therapeutic strategies. Recently, 
      oxazolidinone drugs have been identified as novel anti-tuberculosis drugs 
      effective against drug-resistant M. tuberculosis. However, the effects of these 
      drugs against MAC are still controversial due to limited data. Here, we first 
      evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, 
      linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC 
      strains and one macrolide-resistant M. avium strain in murine bone marrow-derived 
      macrophages (BMDMs) and found that both drugs demonstrated similar potential. The 
      synergistic efficacies with CLR were then determined in a chronic progressive 
      MAC-PD murine model by initiating a 4-week treatment at 8 weeks post-infection. 
      Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs 
      exhibited no anti-MAC effect, and there was no significant difference in the 
      synergistic effect of CLR between LZD and DZD. These findings suggest that 
      oxazolidinone drugs inhibit intracellular bacterial growth, even against 
      macrolide-resistant MAC, but their clinical application requires further 
      consideration.
CI  - (c) 2023. The Author(s).
FAU - Lee, Ju Mi
AU  - Lee JM
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, Seoul, South Korea.
FAU - Kim, Lee-Han
AU  - Kim LH
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College 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 - 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 - Lee, Wonsik
AU  - Lee W
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
FAU - Shin, Sung Jae
AU  - Shin SJ
AD  - Department of Microbiology, Institute for Immunology and Immunological Disease, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, Seoul, South Korea. sjshin@yuhs.ac.
LA  - eng
GR  - NRF-2020M3A9H5104234/Bio & Medical Technology Development Program of National 
      Research Foundation of Korea/
PT  - Journal Article
DEP - 20231123
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Oxazolidinones)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Antitubercular Agents)
RN  - H1250JIK0A (Clarithromycin)
RN  - 0 (Macrolides)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Mycobacterium avium Complex
MH  - *Mycobacterium avium-intracellulare Infection/drug therapy/microbiology
MH  - *Oxazolidinones/pharmacology/therapeutic use
MH  - Anti-Bacterial Agents/pharmacology
MH  - Antitubercular Agents/pharmacology
MH  - Clarithromycin/therapeutic use
MH  - Macrolides/pharmacology
MH  - *Lung Diseases/drug therapy
PMC - PMC10667338
COIS- The authors declare no competing interests.
EDAT- 2023/11/24 00:42
MHDA- 2023/11/27 12:42
PMCR- 2023/11/23
CRDT- 2023/11/23 23:29
PHST- 2023/07/11 00:00 [received]
PHST- 2023/11/21 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/11/24 00:42 [pubmed]
PHST- 2023/11/23 23:29 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - 10.1038/s41598-023-48001-y [pii]
AID - 48001 [pii]
AID - 10.1038/s41598-023-48001-y [doi]
PST - epublish
SO  - Sci Rep. 2023 Nov 23;13(1):20631. doi: 10.1038/s41598-023-48001-y.