Ahmed Samar A, Jordan Rondelle L, Isseroff Roslyn Rivkah, Lenhard Justin R
Department of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA.
Clinical Pharmacy Department, Shefa'a Al-Orman Comprehensive Cancer Center, Luxor 85863, Egypt.
Antibiotics (Basel). 2024 Dec 3;13(12):1165. doi: 10.3390/antibiotics13121165.
The feasibility of repurposing selective serotonin reuptake inhibitors as adjunctive antibacterial agents is an area of current investigation. We sought to evaluate if fluoxetine will achieve synergistic killing with relevant antibacterial drugs against skin and soft tissue pathogens and multidrug-resistant pathogens. : The MIC of fluoxetine was determined using broth microdilution for a diverse isolate collection of 21 organisms. Checkerboard experiments were then conducted using fluoxetine and clinically relevant antibacterial drugs. If fluoxetine and an anti-infective agent achieved synergy denoted by a fractional inhibitory concentration index ≤ 0.5, then the combination was further evaluated in 24 h time-killing experiments. Synergy in time-killing experiments was defined as a ≥2 log CFU/mL reduction in fluoxetine combined with an antibacterial agent at any point in the experiment in comparison to whichever agent in the combination resulted in the lowest bacterial counts individually. : The fluoxetine MICs ranged from 64 to 128 mcg/mL for Gram-positive isolates and 8-512 mcg/mL for Gram-negative organisms. Against Gram-positive isolates, vancomycin, linezolid, clindamycin, and gentamicin failed to achieve synergy in checkerboard experiments. Levofloxacin and fluoxetine were the only combination that demonstrated synergy against a Gram-positive pathogen in both checkerboard and time-killing experiments (1/6 isolates, 16.7%). Against Gram-negative organisms, the most promising combination was fluoxetine and polymyxin B, which achieved synergistic killing in both checkerboard experiments and time-killing experiments in 12/15 isolates (80%). In comparison, fosfomycin and meropenem achieved synergy in both experiments against 6/15 (40%) and 3/15 (20%) Gram-negative isolates, respectively. : The combination of fluoxetine and polymyxin B may be a potential strategy for combatting difficult-to-treat Gram-negative pathogens.
将选择性5-羟色胺再摄取抑制剂重新用作辅助抗菌剂的可行性是当前的一个研究领域。我们试图评估氟西汀是否能与相关抗菌药物协同杀灭皮肤和软组织病原体以及多重耐药病原体。：使用肉汤微量稀释法测定了21种不同菌株的氟西汀最低抑菌浓度（MIC）。然后使用氟西汀和临床相关抗菌药物进行棋盘试验。如果氟西汀和一种抗感染药物达到协同作用，即分数抑菌浓度指数≤0.5，则在24小时杀菌试验中进一步评估该组合。杀菌试验中的协同作用定义为：与组合中单独导致最低细菌计数的任何一种药物相比，在试验的任何时间点，氟西汀与抗菌剂联合使用时细菌菌落形成单位（CFU）/毫升减少≥2个对数。：革兰氏阳性菌分离株中氟西汀的MIC范围为64至128微克/毫升，革兰氏阴性菌的MIC范围为8至512微克/毫升。对于革兰氏阳性菌分离株，在棋盘试验中，万古霉素、利奈唑胺、克林霉素和庆大霉素未达到协同作用。左氧氟沙星和氟西汀是唯一在棋盘试验和杀菌试验中均显示对革兰氏阳性病原体具有协同作用的组合（6株中有1株协同，16.7%）。对于革兰氏阴性菌，最有前景的组合是氟西汀和多粘菌素B，在15株中有12株（80%）在棋盘试验和杀菌试验中均实现了协同杀灭。相比之下，磷霉素和美罗培南在两项试验中分别对6/15（40%）和3/15（20%）的革兰氏阴性菌分离株实现了协同作用。：氟西汀和多粘菌素B的组合可能是对抗难治性革兰氏阴性病原体的一种潜在策略。
