Ofloxacin 내성 마이코박테리아에 대한 Moxifloxacin의 항결핵 효과: Ofloxacin과 Moxifloxacin의 교차내성 연구를 중심으로

Activity of Moxifloxacin Against Ofloxacin-Resistant Mycobacterium Tuberculosis: A Study of Cross-Resistance Between Ofloxacin and Moxifloxacin

  • 김병주 (국립마산병원 임상연구소) ;
  • 강영수 (국립마산병원 임상연구소) ;
  • 박승규 (국립마산병원 임상연구소)
  • Kim, Byoung Ju (Clinical Research Center for Tuberculosis, National Masan Hospital) ;
  • Kang, Young Soo (Clinical Research Center for Tuberculosis, National Masan Hospital) ;
  • Park, Seung Kyu (Clinical Research Center for Tuberculosis, National Masan Hospital)
  • 투고 : 2004.06.15
  • 심사 : 2004.09.15
  • 발행 : 2004.11.30

초록

배 경 : 현재 moxifloxacin은 기존의 quinolone 제제들에 비하여 항결핵효과가 크다고 알려지면서 다제내성 결핵에 많이 사용되어 왔지만 moxifloxacin과 기존의 quinolone간의 교차내성에 대한 보고가 없는 상황에서 기존의 quinolone에 내성인 균주에 대한 moxifloxacin의 효과를 예측하기 어려웠다. 이에 본 연구를 통하여 moxifloxacin과 ofloxacin간의 교차내성을 알아봄으로써 ofloxacin 내성 균주에 대한 moxifloxacin의 항 결핵 효과를 알아보고자 하였다. 방 법 : 2003년 3월부터 2004년 3월까지 폐결핵 치료를 위해서 국립마산병원에 방문 또는 입원하였던 환자들의 객담에서 분리된 M. tuberculosis isolate에 대한 약물감수성 검사상 ofloxacin에 대한 본원 임상 검사실의 내성기준 농도인 $2.5{\mu}g/m{\ell}$의 농도에 내성을 보인 균주 37개와 감성을 보인 균주 16개를 대상으로 하여 ofloxacin 및 moxifloxacin 각각에 대한 MIC를 비례법을 이용하여 조사하였다. 결 과 : Ofloxaicn 감성균주들에 대한 $MIC_{50}$$MIC_{90}$은 ofloxacin에서 모두 $1.25{\mu}g/m{\ell}$, moxifloxacin에서는 각각 $0.31{\mu}g/m{\ell}$$0.63{\mu}g/m{\ell}$였다. ofloxacin 내성균주들에 대한 $MIC_{50}$은 ofloxacin에서 $10{\mu}g/m{\ell}$ 이상, moxifloxacin에서 $5{\mu}g/m{\ell}$였으며 $MIC_{90}$은 ofloxacin과 moxifloxacin 모두에서 $10{\mu}g/m{\ell}$이상의 값을 보였다. 약물 농도 $2.5{\mu}g/m{\ell}$을 기준으로 한 moxifloxacin의 ofloxacin에 대한 교차 내성률은 67.6%로 나타났다. 결 론 : moxifloxacin은 $10{\mu}g/m{\ell}$의 농도에서 ofloxacin 내성균주의 82.4%(28/34)에서 항결핵 효과가 있었으나 ofloxacin 내성을 포함하는 다제내성 결핵환자에게 사용하기 위해서 좀 더 많은 연구가 필요할 것으로 사료된다.

Background : Moxifloxacin is an 8-methoxyquinolone compound which has been shown to have the best activity of the quinolones against M. tuberculosis but there is no literature showing the rate of cross-resistance between moxifloxacin and the other quinolones such as ofloxacin. Therefore, we tested the activity of moxifloxacin against ofloxacin resistant M. tuberculosis by a study of cross-resistance. Methods : We tested MIC's of moxifloxacin and ofloxacin by proportion method against 34 M. tuberculosis isolates showing resistance against ofloxacin at $2.5{\mu}g/m{\ell}$ concentration and 13 ofloxacin susceptible isolates from specimens submitted to clinical laboratory of National Masan Hospital from March 2003 to March 2004. Results : For ofloxacin susceptible isolates, $MIC_{50}$ and $MIC_{90}$ of ofloxacin were all $1.25{\mu}g/m{\ell}$, and $MIC_{50}$ and $MIC_{90}$ of moxifloxacin were $0.31{\mu}g/m{\ell}$ and $0.63{\mu}g/m{\ell}$ respectively. For ofloxacin resistant isolates, $MIC_{50}$ of ofloxacin was over $10{\mu}g/m{\ell}$ and $MIC_{50}$ of moxifloxacin was $5{\mu}g/m{\ell}$, $MIC_{90}$ of ofloxacin and moxifloxacin were all over $10{\mu}g/m{\ell}$. The rate of cross-resistance between the two was 67.6%(23/34) at $2.5{\mu}g/m{\ell}$ concentration. Conclusions : Moxifloxacin showed activity against 82.4%(28/34) of ofloxacin resistant M. tuberculosis at $10{\mu}g/m{\ell}$, but more studies are needed so that moxifloxacin will be used for patient with multi-drug resistant tuberculosis including oflokacin resistance.

키워드

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