Tuberc Respir Dis.  2008 Jun;64(6):422-426.

Detection of Clarithromycin-resistant Strains from Clinical Isolates of Mycobacterium abscessus

• Lee SH
• Park YK
• Ryo SW
• Shim MS
• Lew WJ
• Kim HJ

Abstract

BACKGROUND
Mycobacterium abscessus is the most pathogenic and drug-resistant rapid-growing mycobacterium. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents that have an effect on M. abscessus. We tried to detect the clarithromycin-resistant strains from the clinical isolates of M. abscessus.
METHODS
We tried to isolate the clarithromycin-resistant strains from 220 clinical isolates of M. abscessus by performing using reverse hybridization assay (RHA) and the broth microdilution test (BMT).
RESULTS
Seven resistant strains (3.2%) from all the tested clinical isolates were detected by BMT. Three of these resistant strains were also detected by RHA and it was confirmed that they had point mutants.
CONCLUSION
These results showed that clarithromycin resistance in M. abscessus clinical isolates is related to a point mutation and other unknown mechanisms.

Keyword

Mycobacterium abscessus; Reverse hybridization assay; Broth microdilution test; 23S rRNA; Clarithromycin

MeSH Terms

Anti-Bacterial Agents
Azithromycin
Chimera
Clarithromycin
Mycobacterium
Point Mutation
Anti-Bacterial Agents
Azithromycin
Clarithromycin

Reference

1. Brown-Elliott BA, Griffith DE, Wallace RJ Jr. Newly described or emerging human species of nontuberculous mycobacteria. Infect Dis Clin North Am. 2002. 16:187–220.

2. Brown-Elliott BA, Wallace RJ Jr. Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev. 2002. 15:716–746.

3. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association. Am J Respir Crit Care Med. 1997. 156:S1–S25.

4. Brown BA, Springer B, Steingrube VA, Wilson RW, Pfyffer GE, Garcia MJ, et al. Mycobacterium wolinskyi sp. nov. and Mycobacterium goodii sp. nov., two new rapidly growing species related to Mycobacterium smegmatis and associated with human wound infections: a cooperative study from the International Working Group on Mycobacterial Taxonomy. Int J Syst Bacteriol. 1999. 49:1493–1511.

5. Buriankova K, Doucet-Populaire F, Dorson O, Gondran A, Ghnassia JC, Weiser J, et al. Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex. Antimicrob Agents Chemother. 2004. 48:143–150.

6. Nash KA. Intrinsic macrolide resistance in Mycobacterium smegmatis is conferred by a novel erm gene, erm (38). Antimicrob Agents Chemother. 2003. 47:3053–3060.

7. Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ Jr. Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother. 2005. 55:170–177.

8. Nash KA, Andini N, Zhang Y, Brown-Elliott BA, Wallace RJ Jr. Intrinsic macrolide resistance in rapidly growing mycobacteria. Antimicrob Agents Chemother. 2006. 50:3476–3478.

9. Meier A, Kirschner P, Springer B, Steingrube VA, Brown BA, Wallace RJ Jr, et al. Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob Agents Chemother. 1994. 38:381–384.

10. Nash KA, Inderlied CB. Genetic basis of macrolide resistance in Mycobacterium avium isolated from patients with disseminated disease. Antimicrob Agents Chemother. 1995. 39:2625–2630.

11. Wallace RJ Jr, Meier A, Brown BA, Zhang Y, Sander P, Onyi GO, et al. Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus. Antimicrob Agents Chemother. 1996. 40:1676–1681.

12. Coleman K, Athalye M, Clancey A, Davison M, Payne DJ, Perry CR, et al. Bacterial resistance mechanisms as therapeutic targets. J Antimicrob Chemother. 1994. 33:1091–1116.

13. Fierro JF, Hardisson C, Salas JA. Involvement of cell impermeability in resistance to macrolides in some producer streptomycetes. J Antibiot (Tokyo). 1988. 41:142–144.

14. Honore N, Roche PW, Grosset JH, Cole ST. A method for rapid detection of rifampicin-resistant isolates of Mycobacterium leprae. Lepr Rev. 2001. 72:441–448.

15. NCCLS. Susceptibility testing of Mycobacteria, Nocardia, and other aerobic actinomycetes: approves standard. 2003. Wayne, Pennsylvania: NCCLS.

16. Douthwaite S, Aagaard C. Erythromycin binding is reduced in ribosomes with conformational alterations in the 23S rRNA peptidyl transferase loop. J Mol Biol. 1993. 232:725–731.

17. Goldman RC, Kadam SK. Binding of novel macrolide structures to macrolides-lincosamides-streptogramin B-resistant ribosomes inhibits protein synthesis and bacterial growth. Antimicrob Agents Chemother. 1989. 33:1058–1066.

18. Andersson S, Kurland CG. Elongating ribosomes in vivo are refractory to erythromycin. Biochimie. 1987. 69:901–904.

19. Menninger JR. Mechanism of inhibition of protein synthesis by macrolide and lincosamide antibiotics. J Basic Clin Physiol Pharmacol. 1995. 6:229–250.

20. Champney WS, Tober CL. Superiority of 11,12 carbonate macrolide antibiotics as inhibitors of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Curr Microbiol. 1999. 38:342–348.