Capper-Parkin K L, Nichol T, Smith T J, Lacey M M, Forbes S
Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK.
Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK.
J Hosp Infect. 2023 Apr;134:138-146. doi: 10.1016/j.jhin.2023.02.004. Epub 2023 Feb 18.
Uropathogenic Escherichia coli (UPEC) are a primary cause of catheter-associated urinary tract infections (CAUTIs), often forming mature recalcitrant biofilms on the catheter surface. Anti-infective catheter coatings containing single biocides have been developed but display limited antimicrobial activity due to the selection of biocide-resistant bacterial populations. Furthermore, biocides often display cytotoxicity at concentrations required to eradicate biofilms, limiting their antiseptic potential. Quorum-sensing inhibitors (QSIs) provide a novel anti-infective approach to disrupt biofilm formation on the catheter surface and help prevent CAUTIs.
To evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bactericidal and biofilm eradication concentrations in parallel to assessing cytotoxicity in a bladder smooth muscle (BSM) cell line.
Checkerboard assays were performed to determine fractional inhibitory, bactericidal, and biofilm eradication concentrations of test combinations in UPEC and combined cytotoxic effects in BSM cells.
Synergistic antimicrobial activity was observed between polyhexamethylene biguanide, benzalkonium chloride or silver nitrate in combination with either cinnamaldehyde or furanone-C30 against UPEC biofilms. However, furanone-C30 was cytotoxic at concentrations below those required even for bacteriostatic activity. A dose-dependent cytotoxicity profile was observed for cinnamaldehyde when in combination with BAC, PHMB or silver nitrate. Both PHMB and silver nitrate displayed combined bacteriostatic and bactericidal activity below the half-maximum inhibitory concentration (IC). Triclosan in combination with both QSIs displayed antagonistic activity in both UPEC and BSM cells.
PHMB and silver in combination with cinnamaldehyde display synergistic antimicrobial activity in UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.
尿路致病性大肠杆菌（UPEC）是导尿管相关尿路感染（CAUTIs）的主要病因，常于导尿管表面形成成熟且顽固的生物膜。已研发出含单一杀菌剂的抗感染导尿管涂层，但由于对杀菌剂耐药的细菌群体的出现，其抗菌活性有限。此外，杀菌剂在根除生物膜所需的浓度下通常具有细胞毒性，限制了它们的防腐潜力。群体感应抑制剂（QSIs）为破坏导尿管表面生物膜形成并预防CAUTIs提供了一种新型抗感染方法。
评估杀菌剂与群体感应抑制剂在抑菌、杀菌和根除生物膜浓度下的联合作用，并同时评估其对膀胱平滑肌（BSM）细胞系的细胞毒性。
进行棋盘法试验以确定测试组合在UPEC中的部分抑菌、杀菌和生物膜根除浓度，以及在BSM细胞中的联合细胞毒性作用。
观察到聚六亚甲基双胍、苯扎氯铵或硝酸银与肉桂醛或呋喃酮 - C30联合对UPEC生物膜具有协同抗菌活性。然而，呋喃酮 - C30在甚至低于抑菌活性所需的浓度下就具有细胞毒性。肉桂醛与苯扎氯铵、聚六亚甲基双胍或硝酸银联合时呈现剂量依赖性细胞毒性。聚六亚甲基双胍和硝酸银在低于半数最大抑制浓度（IC）时均表现出联合抑菌和杀菌活性。三氯生与两种群体感应抑制剂联合在UPEC和BSM细胞中均表现出拮抗活性。
聚六亚甲基双胍和银与肉桂醛联合在非细胞毒性浓度下对UPEC具有协同抗菌活性，表明其作为抗感染导尿管涂层剂的潜力。
