To prevent Pseudomonas aeruginosa biofilms in the urinary tract -the search for antibiofilm agents-

在努力寻找抗生素膜剂，我们使用实验模型的复杂性尿路感染（UTI）。我们使用了体外（改良的罗宾斯装置和毛细管生物膜系统）和体内（大鼠）模型。在这些模型中，最近开发的毛细管生物膜系统是一种较好的体外模型，用于评估抗生素膜药物。使用从导管相关性尿路感染患者分离的铜绿假单胞菌OP14-210。在人造尿液的连续流动条件下，在玻璃毛细管中培养生物膜，用激光共聚焦扫描显微镜观察。对潜在的抗菌膜药物进行了评价。磷霉素和氟喹诺酮类药物联合治疗铜绿假单胞菌生物膜是有效的，对生物膜相关感染似乎是有益的。这些药物在体外和体内模型中获得的协同作用，在接受临床口服剂量这些药物治疗的患者尿液中容易达到的浓度下得到证实。我们还研究了铜绿假单胞菌分离株的生物膜形成能力与UTI临床背景/抗菌药物耐药性之间的关系。来自导管相关病例和/或发热期的铜绿假单胞菌分离株的生物膜形成能力高于来自导管无关病例和/或非发热期的分离株。铜绿假单胞菌对哌拉西林、头孢他啶、亚胺培南/西司他汀、庆大霉素和环丙沙星耐药的比例在强生物膜形成者中高于非强生物膜形成者。这些结果表明，铜绿假单胞菌在尿路中的持续存在不仅是由于铜绿假单胞菌本身的多重耐药机制，而且是由于生物膜的形成具有耐药性。

In efforts to search for antibiofilm agents, we use experimental models for complicated urinary tract infections (UTI). We have used in vitro (a modified Robbins device and a capillary biofilm system) and in vivo (rat) models. In these models, a capillary biofilm system recently developed is a better in vitro model for evaluating antibiofilm agents. Pseudomonas aeruginosa OP14-210 isolated from a patient with a catheter-associated UTI was used. The biofilms were grown in glass capillary tubes under continuous flow conditions with artificial urine, and observed by confocal laser scanning microscopy. The potential antibiofilm agents were evaluated. The combination treatment of fosfomycin and fluoroquinolones against P.aeruginosa biofilms was effective and would appear beneficial against biofilm-related infections. This synergy obtained by these in vitro and in vivo models was confirmed at concentrations easily achievable in the urine of patients treated with clinical oral doses of these agents.We also investigated the relationships between biofilm-forming capacities of P.aeruginosa isolates and clinical background / antimicrobial resistance in UTI. The biofilm-forming capacities of P.aeruginosa isolates from catheter-related cases and / or febrile episodes were greater than those from catheter-unrelated cases and / or non-febrile episodes. The percentage of P.aeruginosa isolates exhibiting antimicrobial resistance to piperacillin, ceftazidime, imipenem/cilastatin, gentamicin and ciprofloxacin was higher among strong biofilm formers than among non-strong biofilm formers. These results suggested that the persistence of P.aeruginosa in the urinary tract is due to biofilm formation exhibiting antimicrobial resistance as well as multiple resistance mechanism of P.aeruginosa itself.