DOI QR코드

DOI QR Code

Multi-drug Resistance of Mycoplasma pneumoniae Isolates from Patients with Respiratory Diseases against Quinolone and Macrolide

호흡기질환 환자에서 분리한 Mycoplasma pneumoniae의 Quinolone계와 Macrolide계 항생물질에 대한 다제 저항성

  • Jun, Sung-Gon (Department of Microbiology, Kosin University College of Medicine) ;
  • Chang, Myung-Woong (Department of Microbiology, Kosin University College of Medicine)
  • 전성곤 (고신대학교 의과대학 미생물학교실) ;
  • 장명웅 (고신대학교 의과대학 미생물학교실)
  • Published : 2007.03.30

Abstract

Antimicrobial susceptibility test of the 116 strains of Mycoplasma pneumoniae isolates were performed by a broth micro-dilution method against to moxifloxacin, levofloxacin, sparfloxacin, ofloxacin, ciprofloxacin, clarithromycin minocycline, erythromycin, josamycin, and tetracycline. The initial-minimum inhibitory concentration (I-MIC) was evaluated as the lowest concentration of antimicrobial agents that prevented a color change in the medium at that time when the drug-free growth control, about 7 days after incubation, and the final-minimum inhibitory concentration (F-MIC) was defined a color change about 14 days after incubation. The evaluation to the drug-resistant M. pneumoniae isolates were determined the $MIC{\pm}1.0$ ${\mu}g/ml$ of each antimicrobial agent. According to the I-MIC, single drug-resistant M. pneumoniae strains to ciprofloxacin, ofloxacin, clarithromycin and erythromycin were 79.3, 53.5, 10.3, and 7.8%, respectively. Two kinds of drug-resistant M. pneumoniae strains to ofloxacin and ciprofloxacin, or ciprofloxacin and clarithromycin were 42.2 and 9.5%. Three kinds of drug-resistant M. pneumoniae strains to erythromycin, ofloxacin, and ciprofloxacin, or ofloxacin, ciprofloxacin and clarithromycin were 6.9 and 6.0% . According to the F-MIC, single drug-resistant M. pneumoniae strains to tetracycline, ciprofloxacin, ofloxacin, minocycline,erythromycin, josamycin, clarithromycin and sparfloxacin were 91.4, 91.4, 91.4, 89.7, 68.1, 52.6, 28.5, and 11.2%, respectively. The incidence of two kinds of drug-resistant M. pneumoniae strains were from 20.7% to 91.4%, three kinds of drug-resistant M. pneumoniae strains were from 28.5% to 89.7%, four kinds of drug-resistant M. pneumoniae strains were 2.6%, five kinds of drug-resistant M. pneumoniae were from 2.6% to 21.6%, six kinds of drug-resistant M. pneumoniae strains were from 0.9% to 24.1%, seven kinds of drug-resistant M. pneumoniae strains were from 0.9% to 2.6%, and eight kinds of drug-resistant M. pneumoniae strains were 1.7%. These results suggest that sparfloxacin, moxifloxacin and levofloxacin might be promising antimicrobial agents for the treatment of M. pneumoniae infection in Korea. However, most strains of M. pneumoniae isolates were single or multi-resistance pattern to the other tested antimicrobial agents. Therefore, tetracycline, minocycline, erythromycin, clarithromycin, and second-generation quinolones are more carefully used to patients with M. pneumoniae infection in Korea.

호흡기질환 환자의 상기도 도말물로 부터 분리 동정된 M. pneumoniae 116균주의 moxifloxacin, levofloxacin, sparfloxacin, ofloxacin, ciprofloxacin, clarithromycin minocycline, erythromycin, josamycin, and tetracycline에 대한 감수성 검사를 실시하였다. 각 항생물질에 대한 저항성 균주의 기준은 $MIC{\pm}1.0$ ${\mu}g/ml$ 로 하였으며, 초기 MIC와 최종 MIC를 구분하여 다제 저항성 균주의 분포를 분석하였다. 초기 MIC의 결과로 분리된 균주의 단일 약제에 대한 저항성은 ciprofloxacin이 79.3%, ofloxacin이 53.5%, clarithromycin이 10.3%, erythromycin이 7.8%이었으며, 2가지 약제에 저항성은 ofloxacin과 ciprofloxacin이 42.2%, ciprofloracin과 clarithromycin이 9.5%이었으며, 3가지 약제에 저항성은 erythromycin, ofloxacin과 ciprofloxacin이 6.9%, ofloxacin, ciprofloxacin과 clarithromycin이 6.0%이었다. 최종 MIC의 결과로 분리균의 단일 약제에 대한 저항성은 tetracycline, ciprofloxacin, ofloxacin이 각각 91.4%, minocycline이 89.7%, erythromycin이 68.1%, josamycin이 52.6%, clarithromycin이 28.5%, sparfloxacin이 11.2%이었으며, 2가지 약제에 저항성인 균의 분포는 $20.7{\sim}91.4%$, 3가지약제에 저항성인 규의 분포는 &28.5{\sim}89.7%$, 4가지 약제에 저항성인 균의 분포는 2.6%, 5가지 약제에 저항성인 균은 $2.6{\sim}21.6%$, 6가지 약제에 저항성인 균은 $0.9{\sim}24.1%$이었으며, 7가지 약제에 저항성인 균은 $0.9{\sim}2.6%$이었으며, 8종류 약제에 저항성인 균도 1.7%있었다. 이상의 결과로 국내에서 분리된 M. pneumoniae 균주는 적게는 1-4 종류의 항생제에, 많게는 5-8 종류의 항생제에 저항성인 균주가 있으므로 마이코플라스마폐렴 환자를 치료할때는 macrolide계나 quinolone계의 항생제 선택에 신중을 기하여야 하며, 가급적이면 항생제 감수성 검사를 실시하여 적절한 항생제를 선택함으로써 저항성균의 출현율을 줄일 수 있고 효율적인 치료도 할 수 있도록 하여야 할 것으로 생각된다.

Keywords

References

  1. Arai, S., Y. Gohara, K. Kuwano and T. Kawashima. 1992. Antimycoplasmal activities of new quinolones, tetracyclines, and macrolides against Mycoplasma pneumoniae. Antimicrobial Agents Chemother. 36, 1322-1324 https://doi.org/10.1128/AAC.36.6.1322
  2. Blanchard, A. and C. Bebear, 2002. Mycoplasmas of human, Molecular biology and pathogenicity of mycoplasma, pp 45-71, In Razin S, and Hermann R(1st ed), New York, Kluwer Academic Press, New York
  3. Cassell, G. H., W. A. Clyde and J. K. Davis. 1985. The Mycoplasmas, Mycoplasmal respiratory infections, pp 65-106, Vol. IV, S. Razin and M. F. Barile (1st ed), Academic Press, New York
  4. Cedillo-Ramirez, L., C Gil, I. Zago, A. Yanez and S. Giono. 2000. Association of M. hominis and Ureaplasma urealyticum with some indicators of nonspecific vaginitis. Rev. Latinoam. Microbiol. 42, 1-6
  5. Chang, M. W., K. H. Kim, I. D. Park and M. H. Joh. 1995. Detection of Mycoplasma pneumoniae in clinical specimens of patients by polymerase chain reaction and culture method. J. Korean Soc. Microbiol. 30, 517-525
  6. Chang, M. W., K. H. Kim, I. D. Park, K. H. Kang, E. H. Kong, M. H. Joh, K. E. Kim and S.Y. Park. 2003. Rapid detection of Mycoplasma pneumoniae and antimicrobial susceptibilities of the M. pneumoniae isolates. J. Bacteriol. Virol. 33, 183-191
  7. Chang, M. W., K. H. Kim, I. D. Park, G. Y. Song, S. W. Kim and C.E. Choi. 2005. Isolation of Mycoplasma pneumoniae and antimicrobial susceptibilities of the isolaters(III). J. Life Sci. 15, 479-485 https://doi.org/10.5352/JLS.2005.15.3.479
  8. Chang, M. W., I. D. Park, K. H. Kim, G. Y. Song and S. W. Kim. 2005. Tetracycline and erythromycin resistant mutans of the Mycoplasma pneumoniae isolated from patients with reasipratory diseases. J. Life Sci. 15, 863-870 https://doi.org/10.5352/JLS.2005.15.6.863
  9. Duffy, L. B., D. M. Crabb, X. Bing and K. B. Waites. 2003. Bactericidal activity of levofloxacin against Mycoplasma pneumoniae. J. Antimicrob. Chemother. 52, 527-528 https://doi.org/10.1093/jac/dkg365
  10. Dular, R., R. Kajioka and S. Kasatiya. 1988. Comparison of gene-probe commercial kit and culture technique for the diagnosis of Mycoplasma pneumoniae infection. J. Clin. Microbiol. 26, 1068-1069
  11. Ford, O. K. and J. R. Smith. 1974. Nonspecific urethritis associated with a tetracycline-resistant T-mycoplasama. Br. J. Vener. Dis. 50, 373-377
  12. Kaku, M., K. Ishida, K. Irifune, R. Mizukane, H. Takemura, R. Yoshida, H. Tanaka, T. Usui, K. Tomono, N. Suyama, H. Koga, S. Kohno and K. Hara. 1994. In vitro activities of sparfloxacin against M. pneumoniae. Antimicrobil. Agents Chemother. 38, 738-741 https://doi.org/10.1128/AAC.38.4.738
  13. Kapusinik-Uner, J. E. and M. A. Sande. 1996. Chambers HF: Antimicrobial agents, tetracycline, chloramphenicol, erythromycin, and miscellaneous antimicrobial agents. pp 1123-1153, In Goodman & Gilman's The pharmacological basis of therapeutics, McGraw-Hill, New York, 9th (ed)
  14. Kenny, G. E. and F. D. Cartwright. 1994. Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to new glycycyclines in comparison with those to older tetracyclines. Antimicrob. Agents Chemother. 38, 2628-2632 https://doi.org/10.1128/AAC.38.11.2628
  15. Kenny, G. E. and F. D. Cartwright. 1996. Susceptibilities of M. pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to new quinolone, trovafloxacin(CP-99219). Antimicrob. Agents Chemother. 40, 1048-1049
  16. Krause, D. C. and D. Taylor-Robinson. 1992. Mycoplasma which infect humans. pp 417-444, In Maniloff J. (ed), Mycoplasmas, ASM, Washington
  17. Matsuoka, M., M. Narita, N. Okazki, H. Ohya, T. Yamazaki, K. Ouchi, I. Suzuki, T. Andoh, T. Kenri, Y. Sasaki and T. Sasaki. 2004. Characterization and molecular analysis of macrolide-resistant M. pneumoniae clinical isolates obtained in Japan. Antimicrob. Agents Chemother. 48, 4624-4630 https://doi.org/10.1128/AAC.48.12.4624-4630.2004
  18. Meloni, F., E. Paschetto, P. Mangiarotti, D. I. Crepal, M. Morosini. M. Bulgheroni and A. Fietta. 2004. Acute Chlamydia pneumniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbrations of COPD or asthma: therapeutic considerations. J. Chemother. 16(1), 70-76
  19. Morozumi, M., A. Ito, S.Y. Murayama, K. Hasegawa, R. Kobayashi and K. Ubukata. 2006. Assessment of real-time PCR for diagnosis of M. pneumoniae pneumonia in pediatric patients. Can. J. Microbiol. 52(2), 125-129 https://doi.org/10.1139/W05-118
  20. Morozumi, M., K. Hasegawa, R. Kobayashi, N. Inoue, S. Iwata, H. Kuroki, N. Kawamura, E. Nakayama, T. Tajima, K. Shimizu and K. Ubukata. 2005. Emergence of macrolide-resistant Mycoplasma pneumoniae with a 23S rRNA gene mutation. Antimicrob. Agents Chemother. 49, 2302-2306 https://doi.org/10.1128/AAC.49.6.2302-2306.2005
  21. Okazaki, N., M. Narita, S. Yamada, K. Izumikawa, M. Umetsu, T. Kenri, Y. Sasaki, Y. Arakawa and T. Sasaki. 2001. Characteristics of macrolide-resistant M. pneumoniae strains isolated from patients and induced with erythromycin in vitro. Microbiol. Immunol. 45, 617-620 https://doi.org/10.1111/j.1348-0421.2001.tb01293.x
  22. Park, I. D., K. H. Kim, M. W. Chang and H. S. Park. 1992. Distribution of tetM gene in the tetracycline resistant Bacteria, J. Korean Soc. Microbiol. 27, 59-72
  23. Pereyre, S., P. Gonzalez, B. de Barbeyrac, A. Darnige, H. Renaudin, A. Charron, S. Raherison and C. M. Bebear. 2002. Mutation in 23S rRNA account for intrinsic resistance to macrolides in M. hominis and M. fermentans and for acquired resistance to macrolides in M. hominis. Antimicrob. Agents Chemother. 46, 3142-3150 https://doi.org/10.1128/AAC.46.10.3142-3150.2002
  24. Pereyre, S., C. Guyot, H. Renaudin, A. Charron, C. Bebear and C. M. Bebear. 2004. In vitro selection and characterization of resistance to macrolides and related antibiotics in M. pneumoniae. Antimicrob. Agents Chemother. 48, 460-465 https://doi.org/10.1128/AAC.48.2.460-465.2004
  25. Roberts, M. C., L. A. Koutsky, K. K. Holmes, D. J. LeBlanc and G. E. Kenny. 1985. Tetracycline-resistant Mycoplasma hominis strains contain streptococcal tetM sequences. Antimicrob. agents Chemother, 28, 141-143 https://doi.org/10.1128/AAC.28.1.141
  26. Smith, R. P., A. L. Baltch, W. J. Ritz, A. N. Carpenter, T. A. Halse and L. H. Bopp. 2004. In vitro activities of garenoxacin and levofloxacin against Chlamydia pneumoniae are not affected by presence of Mycoplasma DNA. Antimicrb. Agents Chemother. 48, 2081-2084 https://doi.org/10.1128/AAC.48.6.2081-2084.2004
  27. Suyama, N., K. Ishida, M. Kaku, K. Izumikawa and K. Hara. 1995. Therapeutic activites of macrolides against M. pneumoniae infection. Jap. J. Mycoplasmol. 21, 39-40
  28. Tully, J. G. and D. L. Rose. 1979. Enhanced isolation of Mycoplasma pneumoniae from throat washings with a newly modified culture medium. J. Infect Dis. 139, 478-482 https://doi.org/10.1093/infdis/139.4.478
  29. Vester, B. and S. Douthwaite. 2001. Macrolide resistance conferred by base substitution in 23S rRNA. Antimicrob. Agents Chemother. 45, 1-12 https://doi.org/10.1128/AAC.45.1.1-12.2001
  30. Waites, K. B., L. B. Duffy, T. Schmid, D. Carb, M. S. Pate and G. H. Cassell. 1991. In vitro susceptibilities of Mycoplasma pneumoniae, M. hominis, and Ureaplasma urealyticum to sparfloxacin and PD 127391. Antimicrobial. Agents Chemother. 35, 1181-1185 https://doi.org/10.1128/AAC.35.6.1181