School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
J Hosp Infect. 2021 May;111:78-88. doi: 10.1016/j.jhin.2021.01.024. Epub 2021 Feb 3.
Urinary tract infections (UTIs) are among the most common hospital-acquired infections, with an estimated 75% of UTIs caused by urinary catheters. In addition to the significant healthcare costs and patient morbidity, the escalating antimicrobial resistance reported among common uropathogens make the investigation of efficacious new antimicrobial strategies of urgent importance.
To examine the antibacterial activity of a suite of weak organic acids (WOAs) (citric acid, malic acid, propionic acid, mandelic acid, lactic acid, benzoic acid, pyruvic acid and hippuric acid), alone and in combination, against common nosocomial uropathogens (Proteus mirabilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa).
Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm eradication concentration (MBEC), fractional inhibitory concentration index (FICI) values and kinetics of bactericidal activity of WOAs were determined by microdilution and time-kill assays.
All tested WOAs displayed bactericidal activities against uropathogens in their planktonic and biofilm modes of growth when used individually. Moreover, WOAs in combination displayed synergistic activity against P. mirabilis, S. aureus and E. coli, with reductions in MIC values of up to 250-fold and significant reductions in biofilm formation.
The synergistic multi-mechanistic combinations identified herein are anticipated to play an important role in the treatment and prevention of catheter-associated UTIs.
尿路感染(UTIs)是最常见的医院获得性感染之一,估计有 75%的 UTIs 是由导尿管引起的。除了巨大的医疗保健成本和患者发病率之外,常见尿路病原体报告的抗生素耐药性不断升级,使得调查有效的新抗生素策略变得尤为紧迫。
研究一系列弱有机酸(WOAs)(柠檬酸、苹果酸、丙酸、扁桃酸、乳酸、苯甲酸、丙酮酸和马尿酸)单独和联合对常见医院获得性尿路病原体(奇异变形杆菌、金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌)的抗菌活性。
通过微量稀释和时间杀伤试验测定最小抑菌浓度(MIC)、最小杀菌浓度(MBC)、最小生物膜清除浓度(MBEC)、部分抑菌浓度指数(FICI)值和 WOAs 的杀菌动力学。
所有测试的 WOAs 在浮游和生物膜生长模式下均对尿路病原体具有杀菌活性。此外,WOAs 联合使用对奇异变形杆菌、金黄色葡萄球菌和大肠杆菌表现出协同作用,MIC 值降低了多达 250 倍,生物膜形成显著减少。
本文鉴定的协同多机制组合有望在治疗和预防导管相关 UTIs 中发挥重要作用。