AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
AAC.01551-06v1
51/5/1849    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shen, G.-H.
Right arrow Articles by Chen, J.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, G.-H.
Right arrow Articles by Chen, J.-H.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2007, p. 1849-1851, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01551-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Isepamicin, Other Aminoglycosides, and Capreomycin against Clinical Isolates of Rapidly Growing Mycobacteria in Taiwan{triangledown}

Gwan-Han Shen,1,2 Bo-Da Wu,1 Kun-Ming Wu,3 and Jiann-Hwa Chen2*

Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China,1 Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, Republic of China,2 Rui-Fu-Shi Medical Laboratory, Taichung, Taiwan, Republic of China3

Received 14 December 2006/ Returned for modification 29 December 2006/ Accepted 1 March 2007


   ABSTRACT
Top
 ABSTRACT
TEXT
 REFERENCES
 
The in vitro activities of isepamicin against 117 Mycobacteria abscessus, 48 Mycobacterium fortuitum, and 20 Mycobacterium chelonae isolates were evaluated by a microdilution test. Isepamicin MIC90s were ≤16 µg/ml for the three species. Isepamicin was as active as amikacin and kanamycin and more active than tobramycin, capreomycin, gentamicin, and streptomycin.


   TEXT
Top
 ABSTRACT
 TEXT
REFERENCES
 
Rapidly growing mycobacteria (RGM) can cause a wide spectrum of disseminated or localized diseases, especially pulmonary, skin, or soft tissue infections (6). Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum are the three major pathogenic RGM species. The management of RGM remains very difficult, especially for the problems associated with infection caused by M. abscessus (12).

Aminoglycoside agents have the potential to be extremely active against RGM (1, 5, 15). Amikacin has shown excellent activities against RGM in several studies and currently is the most widely used aminoglycoside in the treatment of RGM (1, 5, 15, 18). Amikacin and isepamicin, an aminoglycoside used in Asia, were developed by introducing the (S)-4-amino-2-hydroxybutyryl and (S)-3-amino-2-hydroxypropionyl side chains into the 1-amino groups of kanamycin and gentamicin, respectively (8). Isepamicin has shown excellent activities against a wide range of bacteria (4). The cyclic peptide capreomycin is sometimes considered an aminoglycoside because of its actions on bacterial ribosomes (7). This study compared the activities of isepamicin with those of five other aminoglycosides (amikacin, gentamicin, kanamycin, tobramycin, and streptomycin) and capreomycin against RGM.

RGM isolates were collected between November 2005 and July 2006 and identified by the conventional biochemical methods (10). Some of these (136 isolates) were confirmed by PCR restriction enzyme analysis of the 65-kDa hsp gene (13). Totals of 117 M. abscessus, 48 M. fortuitum, and 20 M. chelonae nonduplicate clinical isolates were collected. Of them, 71 (61%), 12 (25%), and 7 (35%), respectively, were recovered from patients with probable RGM infections (in which cases identical RGM species were recovered from three or more specimens from the same patient).

Broth microdilution MIC testing was performed according to CLSI guidelines (11, 16-18). The isolates were subcultured on Trypticase soy agar plates with 5% sheep blood (BBL Microbiology Systems) and incubated at 30°C for 72 h. Bacteria on the agar plates were collected and adjusted to a final inoculum (5 x 105 CFU/ml) in cation-supplemented Mueller-Hinton broth (Difco, Detroit, MI). Serial double dilutions of the tested antimicrobial agents were prepared with the same broth, and the concentrations in the wells ranged from 0.25 to 128 µg/ml. The inoculated trays were incubated at 30°C, and MICs were recorded after 3 to 5 days.

RGM isolates with amikacin MICs of ≥64 µg/ml are interpreted as resistant to amikacin and those with amikacin MICs of ≤16 µg/ml as susceptible to amikacin according to the CLSI cutoff criteria (11). No interpretive criteria have been approved for the susceptibilities of RGM to the other six agents except for that of M. chelonae to tobramycin. Quality control strain Staphylococcus aureus ATCC 29213 was included, and the results were in the acceptable range (MICs of 1 to 4 µg/ml).

Table 1 shows the MIC ranges, the MIC50s and MIC90s, and the percentages of isolates with MICs of ≤16, 32, and ≥64 µg/ml for the seven antimicrobial agents against the 185 RGM isolates. It is clear that amikacin, isepamicin, and kanamycin had excellent activities against RGM (MIC50s, 1 to 16 µg/ml; MIC90s, 4 to 32 µg/ml). For these three agents, >87% of the isolates of each of the three RGM species had MICs of ≤16 µg/ml. When MIC50s were compared, isepamicin was found to be onefold more active than amikacin against M. abscessus and M. chelonae and as active as kanamycin against the 185 RGM isolates but sevenfold less active than amikacin against M. fortuitum. When MIC90s were compared, isepamicin was found to be onefold more active than amikacin against M. abscessus, onefold more active than kanamycin against M. fortuitum, and as active as amikacin and kanamycin against M. chelonae but onefold less active than kanamycin against M. abscessus and threefold less active than amikacin against M. fortuitum. Gentamicin exhibited limited activities (MIC50s, 16 to 32 µg/ml; MIC90s, 32 to 64 µg/ml) and streptomycin poor activities (MIC50s, 64 to 128 µg/ml; MIC90s, 128 to >128 µg/ml) against each of the three RGM species. Tobramycin showed excellent activity against M. abscessus and limited to good activities against M. fortuitum and M. chelonae. Capreomycin showed good activity against M. fortuitum but poor activities against M. abscessus and M. chelonae, which is consistent with the results of Lévy-Frébault et al. (9).


View this table:
[in this window]
[in a new window]

  		TABLE 1. In vitro inhibitory activities of amikacin, isepamicin, kanamycin, tobramycin, gentamicin, streptomycin, and capreomycin against 117 isolates of M. abscessus, 48 isolates of M. fortuitum, and 20 isolates of M. chelonae

 
While none of the M. chelonae isolates tested had amikacin or isepamicin MICs of ≥32 µg/ml, 15 (13%) M. abscessus and 3 (6%) M. fortuitum isolates had amikacin and/or isepamicin MICs of ≥32 µg/ml (Table 2). Two M. abscessus isolates (CH10 and R31) were essentially resistant to all of the seven agents tested (MICs, ≥128 µg/ml). For the remaining 13 M. abscessus isolates, isepamicin was either as active as (2 isolates) or one- to threefold more active than (11 isolates) amikacin. Similar phenomena were observed with kanamycin and tobramycin. For the three M. fortuitum isolates with isepamicin MICs of ≥32 µg/ml, amikacin was 7- or 15-fold more active than isepamicin (Table 2). Isepamicin may be a good therapeutic option for RGM isolates that are nonsusceptible to amikacin, and vice versa.


View this table:
[in this window]
[in a new window]

  		TABLE 2. In vitro inhibitory activities of amikacin, isepamicin, kanamycin, tobramycin, gentamicin, streptomycin, and capreomycin against M. abscessus and M. fortuitum isolates that had amikacin MICs of ≥64 or 32 µg/ml and/or isepamicin MICs of ≥64 or 32 µg/ml

 
Because of the high prevalence of antimicrobial resistance in RGM in Taiwan (18), the use of a single agent for treatment is not recommended. Our study indicates that isepamicin, amikacin, and kanamycin exhibited excellent activities against RGM, and tobramycin exhibited excellent activity against M. abscessus. These antimicrobial agents can be used in the combination regimens for RGM. Isepamicin is particularly important since animal and clinical trials have shown that isepamicin is one of the less toxic aminoglycosides (3, 14). The activities of isepamicin against five M. chelonae and M. fortuitum strains were previously reported (2).

Ho et al. (7) found poor activities for amikacin, kanamycin, tobramycin, gentamicin, streptomycin, and capreomycin against M. chelonae and for kanamycin, tobramycin, streptomycin, and capreomycin against M. fortuitum. Only amikacin and gentamicin had good activities against M. fortuitum. Our results are largely different from theirs. The discrepancies may be due to differences in the methods of in vitro testing or the RGM strains used in their studies.


   ACKNOWLEDGMENTS
 
We thank Po-Ren Hsueh for providing M. chelonae isolates.

This study was supported by grants from the Center for Disease Control (DOH 95-DC-1106) and the National Science Foundation (NSC 91-2316-B-005-003-CC3) of Taiwan.


   FOOTNOTES
 
* Corresponding author. Mailing address: Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan 402, Republic of China. Phone: 886-04-22851885. Fax: 886-04-22874879. E-mail: jhchen{at}dragon.nchu.edu.tw Back

{triangledown} Published ahead of print on 12 March 2007. Back


   REFERENCES
Top
 ABSTRACT
 TEXT
 REFERENCES
 

  1. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America. 1997. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am. J. Respir. Crit. Care Med. 156:S1-S25.[Medline]
  2. Barrett, M. S., R. N. Jones, M. E. Erwin, and F. P. Koontz. 1992. CI-960 (PD127391 or AM-1091), sparfloxacin, WIN 57273, and isepamicin activity against clinical isolates of Mycobacterium avium-intracellularae complex, M. chelonae, and M. fortuitum. Diagn. Microbiol. Infect. Dis. 15:169-171.[CrossRef][Medline]
  3. Blum, D. 1995. An overview of the safety of isepamicin in adults. J. Chemother. 7(Suppl. 2):87-93.[Medline]
  4. Cheng, N. C., P. R. Hsueh, Y. C. Liu, J. M. Shyr, W. K. Huang, L. J. Teng, and C. Y. Liu. 2005. In vitro activities of tigecycline, ertapenem, isepamicin, and other antimicrobial agents against clinically isolated organisms in Taiwan. Microb. Drug Resist. 11:330-341.[CrossRef][Medline]
  5. Dalovisio, J. R., G. A. Pankey, R. J. Wallace, and D. B. Jones. 1981. Clinical usefulness of amikacin and doxycycline in the treatment of infection due to Mycobacterium fortuitum and Mycobacterium chelonei. Rev. Infect. Dis. 3:1068-1074.[Medline]
  6. De Groote, M. A., and G. Huitt. 2006. Infections due to rapidly growing mycobacteria. Clin. Infect. Dis. 42:1756-1763.[CrossRef][Medline]
  7. Ho, Y. I., C. Y. Chan, and A. F. Cheng. 1997. In-vitro activities of aminoglycoside-aminocyclitols against mycobacteria. J. Antimicrob. Chemother. 40:27-32.[Abstract/Free Full Text]
  8. Kondo, S., and K. Hotta. 1999. Semisynthetic aminoglycoside antibiotics: development and enzymatic modifications. J. Infect. Chemother. 5:1-9.[Medline]
  9. Lévy-Frébault, V., M. Daffé, K. S. Goh, M. A. Lanéelle, C. Asselineau, and H. L. David. 1983. Identification of Mycobacterium fortuitum and Mycobacterium chelonei. J. Clin. Microbiol. 17:744-752.[Abstract/Free Full Text]
  10. Metchock, B. G., F. S. Nolte, and R. J. Wallace. 1999. Mycobacterium, p. 399-437. In P. R. Murray, E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.), Manual of clinical microbiology, 7th ed. ASM Press, Washington, DC.
  11. National Committee for Clinical Laboratory Standards. 2002. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes. Tentative standards, second edition. M24-T2. National Committee for Clinical Laboratory Standards, Wayne, PA.
  12. Petrini, B. 2006. Mycobacterium abscessus: an emerging rapid-growing potential pathogen. APMIS 114:319-328.[CrossRef][Medline]
  13. Telenti, A., F. Marchesi, M. Balz, F. Bally, E. C. Bottger, and T. Bodmer. 1993. Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis. J. Clin. Microbiol. 31:175-178.[Abstract/Free Full Text]
  14. Tod, M., C. Padoin, and O. Petitjean. 2000. Clinical pharmacokinetics and pharmacodynamics of isepamicin. Clin. Pharmacokinet. 38:205-223.[CrossRef][Medline]
  15. Wallace, R. J., Jr., J. M. Swenson, V. A. Silcox, and M. G. Bullen. 1985. Treatment of nonpulmonary infections due to Mycobacterium fortuitum and Mycobacterium chelonei on the basis of in vitro susceptibilities. J. Infect. Dis. 152:500-514.[Medline]
  16. Woods, G. L. 2000. Susceptibility testing for mycobacteria. Clin. Infect. Dis. 31:1209-1215.[CrossRef][Medline]
  17. Woods, G. L., J. S. Bergmann, F. G. Witebsky, G. A. Fahle, A. Wanger, B. Boulet, M. Plaunt, B. A. Brown, and R. J. Wallace, Jr. 1999. Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. J. Clin. Microbiol. 37:1676-1682.[Abstract/Free Full Text]
  18. Yang, S. C., P. R. Hsueh, H. C. Lai, L. J. Teng, L. M. Huang, J. M. Chen, S. K. Wang, D. C. Shie, S. W. Ho, and K. T. Luh. 2003. High prevalence of antimicrobial resistance in rapidly growing mycobacteria in Taiwan. Antimicrob. Agents Chemother. 47:1958-1962.[Abstract/Free Full Text]

Antimicrobial Agents and Chemotherapy, May 2007, p. 1849-1851, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01551-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
AAC.01551-06v1
51/5/1849    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shen, G.-H.
Right arrow Articles by Chen, J.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, G.-H.
Right arrow Articles by Chen, J.-H.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS