Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance

Go Eun Choi, SungJae Shin, Choul Jae Won, Ki Nam Min, Taegwon Oh, Mi Young Hahn, Keehoon Lee, Soo Hyun Lee, Charles L. Daley, Seonwoo Kim, Byeong Ho Jeong, Kyeongman Jeon, Won Jung Koh

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. Objectives: To compare the activity of CLR and AZM in experimental models. Methods:We compared the treatment efficacies of CLR andAZMand determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. Measurements and Main Results: In all tested M. abscessus isolates, a highlevel of inducibleCLR resistance developed(minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P,0.001).Whereas the AZM MIC increased on Day 14 (P , 0.01 versus Day 3), the level was significantly lower than the CLRMIC onDay 14 (P,0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P , 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P , 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. Conclusions: CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume186
Issue number9
DOIs
Publication statusPublished - 2012 Nov 1

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Mycobacterium Infections
Azithromycin
Clarithromycin
Macrolides
Mycobacterium
Methyltransferases
Erythromycin
Ribosomes
Infection
Gene Expression
Theoretical Models
Anti-Bacterial Agents
Gene Knockout Techniques
Genes

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Choi, Go Eun ; Shin, SungJae ; Won, Choul Jae ; Min, Ki Nam ; Oh, Taegwon ; Hahn, Mi Young ; Lee, Keehoon ; Lee, Soo Hyun ; Daley, Charles L. ; Kim, Seonwoo ; Jeong, Byeong Ho ; Jeon, Kyeongman ; Koh, Won Jung. / Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance. In: American Journal of Respiratory and Critical Care Medicine. 2012 ; Vol. 186, No. 9. pp. 917-925.
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abstract = "Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. Objectives: To compare the activity of CLR and AZM in experimental models. Methods:We compared the treatment efficacies of CLR andAZMand determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. Measurements and Main Results: In all tested M. abscessus isolates, a highlevel of inducibleCLR resistance developed(minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P,0.001).Whereas the AZM MIC increased on Day 14 (P , 0.01 versus Day 3), the level was significantly lower than the CLRMIC onDay 14 (P,0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P , 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P , 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. Conclusions: CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.",
author = "Choi, {Go Eun} and SungJae Shin and Won, {Choul Jae} and Min, {Ki Nam} and Taegwon Oh and Hahn, {Mi Young} and Keehoon Lee and Lee, {Soo Hyun} and Daley, {Charles L.} and Seonwoo Kim and Jeong, {Byeong Ho} and Kyeongman Jeon and Koh, {Won Jung}",
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Choi, GE, Shin, S, Won, CJ, Min, KN, Oh, T, Hahn, MY, Lee, K, Lee, SH, Daley, CL, Kim, S, Jeong, BH, Jeon, K & Koh, WJ 2012, 'Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance', American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 9, pp. 917-925. https://doi.org/10.1164/rccm.201111-2005OC

Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance. / Choi, Go Eun; Shin, SungJae; Won, Choul Jae; Min, Ki Nam; Oh, Taegwon; Hahn, Mi Young; Lee, Keehoon; Lee, Soo Hyun; Daley, Charles L.; Kim, Seonwoo; Jeong, Byeong Ho; Jeon, Kyeongman; Koh, Won Jung.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 186, No. 9, 01.11.2012, p. 917-925.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance

AU - Choi, Go Eun

AU - Shin, SungJae

AU - Won, Choul Jae

AU - Min, Ki Nam

AU - Oh, Taegwon

AU - Hahn, Mi Young

AU - Lee, Keehoon

AU - Lee, Soo Hyun

AU - Daley, Charles L.

AU - Kim, Seonwoo

AU - Jeong, Byeong Ho

AU - Jeon, Kyeongman

AU - Koh, Won Jung

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. Objectives: To compare the activity of CLR and AZM in experimental models. Methods:We compared the treatment efficacies of CLR andAZMand determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. Measurements and Main Results: In all tested M. abscessus isolates, a highlevel of inducibleCLR resistance developed(minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P,0.001).Whereas the AZM MIC increased on Day 14 (P , 0.01 versus Day 3), the level was significantly lower than the CLRMIC onDay 14 (P,0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P , 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P , 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. Conclusions: CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.

AB - Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. Objectives: To compare the activity of CLR and AZM in experimental models. Methods:We compared the treatment efficacies of CLR andAZMand determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. Measurements and Main Results: In all tested M. abscessus isolates, a highlevel of inducibleCLR resistance developed(minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P,0.001).Whereas the AZM MIC increased on Day 14 (P , 0.01 versus Day 3), the level was significantly lower than the CLRMIC onDay 14 (P,0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P , 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P , 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. Conclusions: CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.

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