Programa de Pós-Graduação Em Ciências Farmacêuticas, Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil.
Departamento de Análises Clínicas E Toxicológicas, Universidade Federal de Santa Maria (UFSM), Prédio 2626, Sala 1201, Santa Maria, Rio Grande Do Sul, 97015-900, Brazil.
World J Microbiol Biotechnol. 2021 Feb 19;37(3):53. doi: 10.1007/s11274-021-03016-3.
The repositioning of drugs has been shown to be an advantageous alternative for treating diseases caused by multidrug-resistant (MDR) microorganisms. The study aimed to investigate the in vitro antibacterial activity of the antidepressants fluoxetine and paroxetine alone and in combination with the antibacterial ciprofloxacin against standard strains and clinical isolates to explore the repositioning of these drugs in severe bacterial infections. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), tolerance level, fractional inhibitory concentration index (FICI) and interaction of antidepressants with the ciprofloxacin antibiotic were determined using the Checkerboard method against six American Type Culture Collection (ATCC) standard strains and seventy MDR clinical isolates. Both antidepressants showed better antibacterial activity than ciprofloxacin, in addition to being separately bactericidal against all tested Gram-negative and Gram-positive strains. When associated with ciprofloxacin, fluoxetine and paroxetine exhibited significant synergism compared to seventy ciprofloxacin-resistant clinical isolates, demonstrating that these antidepressants were able to increase the antibacterial activity of the antibiotic by eight times. The combination of antidepressants with ciprofloxacin showed relatively better activity against Acinetobacter baumannii, Enterococcus faecium and Klebsiella pneumoniae, strains in which the FICI value obtained was 0.008. The MDR isolates tested in this study ratify the antibacterial properties of the non-antibiotic fluoxetine and paroxetine. In addition, synergism when associated with ciprofloxacin is an alternative for treating serious infections in hospitalized patients. However, additional in vivo studies must be conducted to elucidate the mechanisms of action of these drugs.
药物重定位已被证明是治疗多药耐药（MDR）微生物引起的疾病的有利替代方法。本研究旨在研究单独使用抗抑郁药氟西汀和帕罗西汀以及与抗菌药环丙沙星联合使用对标准菌株和临床分离株的体外抗菌活性，以探索这些药物在严重细菌感染中的重定位作用。使用棋盘法测定最低抑菌浓度（MIC）、最低杀菌浓度（MBC）、耐量水平、部分抑菌浓度指数（FICI）以及抗抑郁药与环丙沙星抗生素的相互作用，共针对 6 株美国典型培养物保藏中心（ATCC）标准菌株和 70 株 MDR 临床分离株进行了测试。两种抗抑郁药的抗菌活性均优于环丙沙星，并且对所有测试的革兰氏阴性和革兰氏阳性菌株均具有单独的杀菌作用。与环丙沙星联合使用时，氟西汀和帕罗西汀与 70 株环丙沙星耐药的临床分离株相比表现出显著的协同作用，表明这些抗抑郁药能够使抗生素的抗菌活性增加 8 倍。抗抑郁药与环丙沙星的联合使用对鲍曼不动杆菌、屎肠球菌和肺炎克雷伯菌表现出相对更好的活性，获得的 FICI 值为 0.008。本研究中测试的 MDR 分离株证实了非抗生素氟西汀和帕罗西汀的抗菌特性。此外，与环丙沙星联合使用的协同作用是治疗住院患者严重感染的一种替代方法。然而，必须进行更多的体内研究来阐明这些药物的作用机制。
