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선택가능한 치료제 후보를 확대하기 위한 다제내성 Acinetobacter baumannii에 대한 linalool 및 colistin 병합요법의 상승효과 평가

Evaluation of Synergistic Effect of Combined Treatment with Linalool and Colistin on Multidrug-Resistant Acinetobacter baumannii to Expand Candidate for Therapeutic Option

김동민|강성호|김춘미|고영진|박건|이슬비|조성식|안영준|국중기|임동훈|윤나라|정석훈|장숙진|김웅전
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2020.03|Annals of Clinical Microbiology|제23권 제1호|pp. 1-10|DOI 10.5145/ACM.2020.23.1.11

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키워드

SynergyAcinetobacter baumanniiColistinLinaloolTime-kill assay

초록

배경: Acinetobacter baumannii는 약제내성의 증가로 세계적인 문제로 대두되고 있다. 다제내성 A. baumannii (MDRAB)감염의 치료법이 제한적이므로 새로운 치료법의 발견이 시급하다. Linalool 은 Coriandrum sativum의 주요 구성요소로서 최근 A. baumannii에 대한 높은 항균효과를 가지고 있음이 밝혀졌다. 이 연구의 목적은 MDRAB와 광범위내성 A. baumannii (XDRAB)에 대하여 linalool 과 colistin의 조합이 상승효과를 보이는지 조사하기 위함이다. 방법: A. baumannii 51균주로 실험하였으며 10균주의 MDRAB와 41균주의 XDRAB로 구성되었다. Broth microdilution으로 linalool의 MIC를 결정하였고 time-kill assay로 약제의 작용을 평가하였다. 결과: 51균주의 A. baumannii 임상분리주를 대상으로 Time-kill assay 시행한 결과 기준 2를 적용시, 높은 상승작용(92.1%), 낮은 무관(7.8%), 그리고 높은 살균효과(74.5%)가 관찰되었다. Linalool과colistin조합의 상승효과는 MDRAB와 XDRAB에서 각각 96%와 92.1%로 관찰되었다. 길항작용은관찰되지 않았다. 결론: Linalool과 colistin의 조합은 높은 상승작용률을 보여 MDRAB감염을 관리하는 효과적인 조합일 가능성을 보여주었다. 그러므로 이 조합의 MDRAB감염치료에 대한 효율성을 평가하기 위해 in vivo 추가연구가 필요하다.

Abstract

Background: Acinetobacter baumannii infection is a significant health problem worldwide due to increased drug resistance. The limited antimicrobial alternatives for the treatment of severe infections by multidrug-resistant A. baumannii (MDRAB) make the search for other therapeutic options more urgent. Linalool, the major oil compound in Coriandrum sativum, was recently found to have high antibacterial activity against A. baumannii. The purpose of this study was to investigate the synergistic effect of linalool and colistin combinations against MDRAB and extensively drug-resistant A. baumannii (XDRAB). Methods: A total of 51 strains of A. baumannii clinical isolates, consisting of 10 MDRAB and 41 XDRAB were tested. We determined the minimum inhibitory concentration (MIC) of linalool for the test strains using the broth microdilution method and searched for interactions using the time-kill assay. Results: The time-kill assay showed that the linalool and colistin combination displayed a high rate of synergy (92.1%) (by synergy criteria 2), low rate of indifference (7.8%), and a high rate of bactericidal activity (74.5%) in the 51 clinical isolates of A. baumannii. The synergy rates for the linalool and colistin combination against MDRAB and XDRAB were 96% and 92.1%, respectively. No antagonism was observed for the linalool and colistin combination. Conclusions: The combination of linalool and colistin showed a high synergy rate, which may be beneficial for controlling MDRAB infections. Therefore, this combination is a good candidate for in vivo studies to assess its efficacy in the treatment of MDRAB infections.

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