ABSTRACT

Introduction

Urinary tract infections (UTIs) are extremely common. Millions of people, particularly healthy women, are affected worldwide every year. One-in-two women will have a recurrence within 12-months of an initial UTI. Inadequate treatment risks worsening infection leading to acute pyelonephritis, bacteremia and sepsis. In an era of increasing antimicrobial resistance, it is critical to provide optimized antimicrobial treatment.

Areas covered

Literature was searched using PubMed and Google Scholar (up to 06/2020), examining the etiology, diagnosis and oral antimicrobial therapy for uncomplicated UTIs, with emphasis on urinary antimicrobial pharmacokinetics (PK) and the application of dynamic in vitro models for the pharmacodynamic (PD) profiling of pathogen response.

Expert opinion

The majority of antimicrobial agents included in international guidelines were developed decades ago without well-described dose–response relationships. Microbiology laboratories still apply standard diagnostic methodology that has essentially remained unchanged for decades. Furthermore, it is uncertain how relevant standard in vitro susceptibility is for predicting antimicrobial efficacy in urine. In order to optimize UTI treatments, clinicians must exploit the urine-specific PK of antimicrobial agents. Dynamic in vitro models are valuable tools to examine the PK/PD and urodynamic variables associated with UTIs, while informing uropathogen susceptibility reporting, optimized dosing schedules, clinical trials and treatment guidelines.

中文翻译：

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抗菌药代动力学和临床前体外模型，以支持无并发症下尿路感染的优化治疗方法

摘要

介绍

尿路感染 (UTI) 极为常见。全世界每年有数百万人，尤其是健康妇女受到影响。有二分之一的女性会在初次尿路感染后的 12 个月内复发。治疗不当会导致感染恶化，导致急性肾盂肾炎、菌血症和败血症。在抗菌素耐药性不断增加的时代，提供优化的抗菌治疗至关重要。

覆盖区域

使用 PubMed 和 Google Scholar 搜索文献（截至 06/2020），检查无并发症 UTI 的病因、诊断和口服抗菌治疗，重点是尿液抗菌药代动力学 (PK) 和动态体外模型的药效学应用。PD) 分析病原体反应。

专家意见

国际指南中包含的大多数抗菌药物是几十年前开发的，没有充分描述的剂量反应关系。微生物实验室仍然采用几十年来基本保持不变的标准诊断方法。此外，尚不确定体外敏感性标准对于预测尿液中的抗菌功效的相关性。为了优化 UTI 治疗，临床医生必须利用抗菌药物的尿液特异性 PK。动态体外模型是检查与 UTI 相关的 PK/PD 和尿动力学变量的宝贵工具，同时为尿路病原体敏感性报告、优化给药方案、临床试验和治疗指南提供信息。