Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, Brazil; Christus University Center, Fortaleza, Ceará, Brazil.
Microb Pathog. 2024 Aug;193:106769. doi: 10.1016/j.micpath.2024.106769. Epub 2024 Jun 30.
The bacterium Escherichia coli is one of the main causes of urinary tract infections. The formation of bacterial biofilms, especially associated with the use of urinary catheters, contributes to the establishment of recurrent infections and the development of resistance to treatment. Strains of E. coli that produce extended-spectrum beta-lactamases (ESBL) have a greater ability to form biofilms. In addition, there is a lack of drugs available in the market with antibiofilm activity. Promethazine (PMZ) is an antihistamine known to have antimicrobial activity against different pathogens, including in the form of biofilms, but there are still few studies of its activity against ESBL E. coli biofilms. The aim of this study was to evaluate the antimicrobial activity of PMZ against ESBL E. coli biofilms, as well as to assess the application of this drug as a biofilm prevention agent in urinary catheters. To this end, the minimum inhibitory concentration and minimum bactericidal concentration of PMZ in ESBL E. coli strains were determined using the broth microdilution assay and tolerance level measurement. The activity of PMZ against the cell viability of the in vitro biofilm formation of ESBL E. coli was analyzed by the MTT colorimetric assay and its ability to prevent biofilm formation when impregnated in a urinary catheter was investigated by counting colony-forming units (CFU) and confirmed by scanning electron microscopy (SEM). PMZ showed bactericidal activity and significantly reduced (p < 0.05) the viability of the biofilm being formed by ESBL E. coli at concentrations of 256 and 512 μg/ml, as well as preventing the formation of biofilm on urinary catheters at concentrations starting at 512 μg/ml by reducing the number of CFUs, as also observed by SEM. Thus, PMZ is a promising candidate to prevent the formation of ESBL E. coli biofilms on abiotic surfaces.
大肠杆菌是尿路感染的主要病因之一。细菌生物膜的形成，特别是与使用导尿管有关，有助于建立复发性感染和对治疗产生耐药性。产生扩展谱β-内酰胺酶（ESBL）的大肠杆菌菌株具有更强的形成生物膜的能力。此外，市场上缺乏具有抗生物膜活性的药物。吩噻嗪（PMZ）是一种已知具有抗微生物活性的抗组胺药，对包括生物膜形式在内的不同病原体均有效，但对其针对 ESBL 大肠杆菌生物膜的活性研究仍然较少。本研究旨在评估 PMZ 对 ESBL 大肠杆菌生物膜的抗菌活性，并评估该药物作为预防生物膜的药物在导尿管中的应用。为此，使用肉汤微量稀释法和耐量测定法测定 PMZ 在 ESBL 大肠杆菌菌株中的最低抑菌浓度和最低杀菌浓度。通过 MTT 比色法分析 PMZ 对 ESBL 大肠杆菌体外生物膜形成的细胞活力的活性，并通过计算集落形成单位（CFU）和通过扫描电子显微镜（SEM）确认来研究其在浸渍在导尿管中时预防生物膜形成的能力。PMZ 显示出杀菌活性，并显著降低（p<0.05）ESBL 大肠杆菌形成的生物膜的活力，在 256 和 512μg/ml 浓度下，以及在 512μg/ml 浓度下开始通过减少 CFU 来预防生物膜在导尿管上的形成，SEM 也观察到了这一点。因此，PMZ 是预防生物膜在非生物表面上形成的有前途的候选药物。
