다약제 내성 Pseudomonas aeruginosa에 대한 항생제 병합 효과

In Vitro Effects of Combined Antibiotics against Multidrug-resistant Pseudomonas aeruginosa

  • 배현주 (한양대학교 의과대학 감염내과학교실)
  • Pai, Hyun-Joo (Infectious Diseases, Hanyang University College of Medicine)
  • 투고 : 2010.01.25
  • 심사 : 2010.04.09
  • 발행 : 2010.07.01

초록

목적: ${\beta}$-lactam, fluoroquinolone 및 amikacin에 내성인 다약제 내성 Pseudomonas aeruginosa 임상균주를 대상으로 여러 항생제의 단독 혹은 병합 투여의 균 억제 효과를 실험적으로 확인하고자 하였다. 방법: Ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin 및 amikacin에 다양한 수준의 내성을 보이는 임상균주 10주를 대상으로 checkerboard법과 in vitro killing assay로 항생제의 병합요법의 효과를 판정하였다. 결과: Checkerboard법의 결과로는 ciprofloxacin에 비하여 amikacin을 병합하였을 때 상승효과가 높았다. Ceftazidime, cefepime, piperacillin/tazobactam 및 meropenem과의 상승효과는 ciprofloxacin의 MIC가 낮을수록 저명하였고, MIC가 16 ${\mu}g$/mL 이상인 균주에서는 모두 indifference 효과를 보였다. 반면에, amikacin은 MIC가 128 ${\mu}g$/mL인 경우도 ceftazidime, cefepime, piperacillin/tazobactam 및 meropenem과 병합시 상승효과를 보였다. 그러나 in vitro killing assay에서는 meropenem 내성이면서 ciprofloxacin의 MIC가 16 ${\mu}g$/mL인 균주에서도 meropenem과 ciprofloxacin의 병합요법에 상승 살균 효과를 보였다. Amikacin은 checkerboard법의 결과와 달리 ceftazidime 혹은 piperacillin/tazobactam과 상승효과를 보이지 않았고 meropenem과 상승효과를 보였으며 MIC가 128 ${\mu}g$/mL인 고도 내성균도 같은 상승효과를 보였다. 결론: 임상적으로 내성 수준을 알 수 없는 다제내성 P. aeruginosa 감염시 일단은 meropenem과 amikacin 병합요법을 써 볼 수 있을 것으로 사료되며 이후 실험적으로 checkerboard법이나 in vitro killing assay 결과를 확인한 후 약을 수정하는 것이 좋겠다.

Background/Aims: The inhibitory effects of the combination of ${\beta}$-lactam with ciprofloxacin or amikacin against clinical isolates of multidrug-resistant Pseudomonas aeruginosa were evaluated. Methods: This study examined ten isolates with variable levels of resistance to ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, and amikacin. The efficacy of the combined antibiotics was studied using a checkerboard method or in vitro killing assay. Results: The combination of ceftazidime, cefepime, aztreonam, piperacillin-tazobactam, or meropenem with amikacin showed synergistic effects for all of the strains regardless of the minimum inhibitory concentration (MIC) of amikacin, but combination with ciprofloxacin showed a synergistic effect for the isolate with a low MIC of ciprofloxacin by the checkerboard method. The isolates with a high MIC of ciprofloxacin showed an indifferent effect in combination with ${\beta}$-lactam and ciprofloxacin. The in vitro killing assay showed that meropenem with ciprofloxacin acted synergistically for the isolates with a MIC of 16 ${\mu}g$/mL of ciprofloxacin. However, amikacin showed synergistic effects with meropenem for the isolates with high-level resistance against amikacin, i.e., up to an MIC of 128 ${\mu}g$/mL. Contrary to the checkerboard method results, no synergy was observed for the combination of ceftazidime/piperacillin-tazobactam and amikacin. Conclusions: Meropenem with amikacin can be the first choice for infections caused by multidrug-resistant P. aeruginosa when the level of resistance is not known.

키워드

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