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광범위 약제내성 Acinetobacter baumannii 균주에 대한 7가지 항균물질 조합의 상승 효과 평가

Assessment of the Synergistic Effect of Seven Antimicrobial Combinations on Extensively Drug- Resistant Acinetobacter baumannii Strains

강성호|고영진|박건|김춘미|최지예|장숙진
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2022.12|Annals of Clinical Microbiology|제25권 제4호|pp. 133-144|DOI 10.5145/ACM.2022.25.4.3

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키워드

SynergyMinocyclineDrug CombinationsColistinAntimicrobial cationic peptides

초록

배경: Extensively drug-resistant Acinetobacter baumannii (XDRAB)에 감염된 환자를 위한 적절한 치료제를 찾기 어려운 문제를 해결하기 위해 항균제의 치료효과를 높이기 위한 다양한 전략 개발이필요하다. 본 연구의 목적은 7가지 항균물질 조합의 효과를 비교하여 그 중 우수한 병합효과를 보이는 조합을 선별하는데 있다. 방법: 대상균주는 XDRAB 균주 7주였다. 7가지 약제조합의 구성은 colistin을 기본으로 넣고 7가지 항균물질(doripenem, minocycline, tigecycline, linezolid, fusidic acid, vancomycin, 및 alyteserin peptidee4k) 중 하나씩 각각 넣어 조성하였다. Time-kill 분석을 이용하여 상승효과율을 측정함으로서 각조합에 들어간 약물간 상호작용을 평가하였다. 결과: 본 연구에서 time-kill 분석법으로 실험한 7가지 약제조합의 상승효과율이 가장 높았던 조합부터 내림차순으로 열거해보면 colistin + minocycline 조합(57.1%), colistin + alyteserin E4K 조합(50.0%), colistin + tigecycline 조합(42.9%), colistin + vancomycin조합(28.6%), colistin + doripenem 조합(14.3%)과 colistin + fusidic acid 조합(14.3%), colistin + linezolid 조합 (0%)의 순이었다. 길항작용을보인 조합은 없었다. 살균능을 보인 3 조합과 그 살균비율은 colistin + alyteserin E4K 조합(33.3%),colistin + minocycline 조합(14.3%)과 colistin + vancomycin 조합(14.3%)이었다. 결론: 7가지 약제조합 중 높은 상승효과율을 보인 colistin + minocycline 조합과 colistin + alyteserinE4K 조합은 XDRAB 균주에 대한 항균제의 병합 효과를 평가하기 위한 향후 생체내 실험에서 유망한 후보들로 간주될 수 있다고 생각된다.

Abstract

Background: To solve the difficulty in determining the appropriate treatment regimen forpatients infected with extensively drug-resistant Acinetobacter baumannii (XDRAB), it isnecessary to develop various strategies to increase the therapeutic effect of antimicrobialagents. The purpose of this study was to select the treatment combination showing thegreatest antimicrobial effect among seven candidate antimicrobial substances. Methods: Seven strains of XDRAB were used in this study. The composition of the treatmentconsisted of colistin as the base and one of the seven antimicrobial substances, doripenem,minocycline, tigecycline, linezolid, fusidic acid, vancomycin, or alyteserin E4K peptide. Theinteraction between the drugs in each combination was evaluated by measuring the synergyrates using time-kill analysis. Results: The synergy rates of the seven combinations tested in the time-kill assay in thisstudy were as follows, in descending order from the combination with the highest synergyrate: colistin + minocycline (57.1%), colistin + alyteserin E4K (50.0%), colistin + tigecycline(42.9%), colistin + vancomycin (28.6%), colistin + doripenem (14.3%), colistin + fusidic acid(14.3%), and colistin + linzolid (0%). None of the combinations showed antagonism. The threecombinations showing bactericidal activity and the rates of their bactericidal activity werecolistin + alyteserin E4K combination (33.3%), colistin + minocycline (14.3%), and colistin +vancomycin (14.3%). Conclusion: The colistin + minocycline and colistin + alyteserin E4K treatment combinations,which showed high synergy rates, can be considered as promising candidates for future invivo experiments evaluating combination therapies.

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In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii박건, 강성호, 김춘미, 문대수, 박균철, 장숙진, 정석훈, 최인선, 최지애대한진단검사의학회 · Annals of Laboratory Medicine2016 · 제36권 제2호다제내성 Acinetobacter baumannii 균주의 항균제 병합 효과문희원, 이미애대한진단검사의학회 · Annals of Laboratory Medicine2005 · 제25권 제5호In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates어영, 송원근, 신희봉, 용동은, 이경원, 이혁민, 정석훈, 홍성근, Kyung Ho Roh대한진단검사의학회 · Annals of Laboratory Medicine2016 · 제36권 제2호Imipenem 내성 Acinetobacter baumannii에서 항균제 병합요법의 시험관내 상승작용 검사김미나, 성흥섭, 유수진, 최수진대한진단검사의학회 · Annals of Laboratory Medicine2007 · 제27권 제2호선택가능한 치료제 후보를 확대하기 위한 다제내성 Acinetobacter baumannii에 대한 linalool 및 colistin 병합요법의 상승효과 평가박건, 강성호, 고영진, 국중기, 김동민, 김웅전, 김춘미, 안영준, 윤나라, 이슬비, 임동훈, 장숙진, 정석훈, 조성식대한임상미생물학회 · Annals of Clinical Microbiology2020 · 제23권 제1호국내의 Acinetobacter baumannii와 Pseudomonas aeruginosa 임상분리주에 대한 Colistin과 Polymyxin B의 감수성 양상김재석, 김한성, 박민정, 송원근, 우흥정, 이규만, 이태재대한감염학회 · Infection and Chemotherapy2006 · 제38권 제6호

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