미생물학회지 (Korean Journal of Microbiology)

  • 제44권4호
  • /
  • Pages.339-345
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  • 2008
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  • 0440-2413(pISSN)
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  • 2383-9902(eISSN)
한국미생물학회 (The Microbiological Society of Korea)
권호 표지

Metallo-${\beta}$-lactamase를 생성하여 Imipenem에 내성인 Pseudomonas aeruginosa에 대한 항균제 병합요법의 효과

Effect of Antibiotic Combination Therapy on Metallo-${\beta}$-Lactamase Producing Imipenem Resistant Pseudomonas aeruginosa

  • 홍승복 (단국대학교 첨단과학부 미생물학 및 기초과학연구소) ;
  • 김홍철 (단국대학교 첨단과학부 미생물학 및 기초과학연구소) ;
  • 이장원 (단국대학교 첨단과학부 미생물학 및 기초과학연구소) ;
  • 손승렬 (단국대학교 첨단과학부 미생물학 및 기초과학연구소)
  • Hong, Seung-Bok (Department of Microbiology and Institute of Basic Sciences, Dankook University) ;
  • Kim, Hong Chul (Department of Microbiology and Institute of Basic Sciences, Dankook University) ;
  • Lee, Jang-Won (Department of Microbiology and Institute of Basic Sciences, Dankook University) ;
  • Son, Seung-Yeol (Department of Microbiology and Institute of Basic Sciences, Dankook University)
  • 발행 : 2008.12.31
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초록

국내 대학병원에서 분리되어 imipenem 에 대한 최소억제농도가 $8{\mu}g/ml$ 이상인 51개의 포도당비발효 그람음성 간균들 중 metallo-${\beta}$-lactamase (MBL)을 생성하는 균주들을 분리하고, 그들 중에서 내성이 강한 Pseudomonas aeruginosa에 대한 항균제 병합요법의 효과를 알아보기 위하여 상승효과를 보이는 항균제 조합을 찾아보았다. 9개의 균주(Pseudomonas aeruginosa 2주 및 Achromobacter xylosoxidans subsp. xylosoxidans 7주)가 MBL 양성을 나타냈으며, PCR 결과 9주 모두에서 $bla_{VIM-2}$ 유전자가 관찰되었다. 이들 중에서 P. aeruginosa DK569는 aztreonam (MIC; $8{\mu}g/ml$)을 제외하고 실험한 모든 ${\beta}$-lactam 항균제, aminoglycoside, ciprofloxacin에 내성을 보여 aztreonam 함유 배지를 이용하여 상승효과률 보이는 항균제를 찾고자 하였다. One disk synergy test 에서 선별된 항균제 조합을 이용하여 생존률 검사 실험을 한 결과, aztreonam (AZT)와 piperacillin-tazobactam (TZP)의 병합은 항균제 노출 6시간 후에 AZT 또는 TZP의 단독 항균제 노출시 보다 균수가 1/18.7로 감소하였다. 그리고 AZT와 amikacin (AN)의 병합에서도 항균제 노출 6 시간 후에 AZT 또는 AN의 단독항균제의 투여보다 균수가 1/17.1 로 감소하였다. 결국 위 두 조합은 의미있는 상승효과를 보이지 못하여 위 세 항균제를 조합하여 실험하였다. 위의 세 항균제를 병합하였을 때 항균제 노출 8시간 후에 AZT, TZP 및 AN의 단독 투여에 비하여 병합요법에 의해 균수가 1/183.3 로 감소하여 의미있는 상승효과를 보였다. 이 결과는 치료가 쉽지 앓은 MBL 생성균에 의한 감염에 대한 치료에 AZT, TZP 및 AN의 세 가지 항균제 병합요법이 유용할 것이라는 것을 의미한다.

This study was to detect MBL (metallo-${\beta}$-lactamase) among glucose non-fermenting Gram-negative bacilli isolated from clinical specimen and to search antimicrobial combination therapy against MBL producing Pseudomonas aeruginosa. Among fifty one isolates of Gram-negative bacilli with reduced imipenem susceptibility ($MIC{\ge}8{\mu}g/ml$), nine isolates have shown positive results in MBL detection test. They were seven Achromobacter xylosoxidans subsp. xylosoxidans and two P. aeruginosa. The results from EDTA-DDST coin-cided with those of PCR and nucleotide sequence analysis which showed the presence of $bla_{VIM-2}$. The combination of aztreonam (AZT) and piperacillin-tazobactarn (TZP) or AZT and amikacin (AN) screened by one disk synergy test showed no synergistic effect. Triple antibiotic combination therapy with AZT, TZP and AN, however, was shown to be effective and the most synergistic after 8 hrs of exposure. This result strongly suggest that the triple combination therapy of AZT, TZP, and AN could be useful for the treatment of infection caused by MBL producing Gram-negative bacilli.

키워드

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