Department of Urology, Santa Chiara Regional Hospital, Trento, Italy; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy.
Int J Antimicrob Agents. 2023 Dec;62(6):106983. doi: 10.1016/j.ijantimicag.2023.106983. Epub 2023 Sep 24.
The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe.
全球范围内由多药耐药性大肠杆菌引起的单纯性下尿路感染（uUTI）的患病率正在上升。为了解决这一紧急情况，国际指南建议减少氟喹诺酮类药物的使用，因为这些药物的耐药性不断增加，且具有长期和潜在致残的副作用。替代氟喹诺酮类药物的首选药物是磷霉素氨丁三醇（FT），这是一种众所周知的磷酸衍生物，对革兰氏阴性和革兰氏阳性细菌具有广谱活性，包括多药耐药（MDR）菌株。欧洲抗菌药物敏感性测试委员会（EUCAST）最近将用于 uUTI 的 FT 的大肠杆菌药敏折点从 32mg/L 降低到 8mg/L。这可能会导致针对大肠杆菌和其他微生物的口服磷霉素靶向治疗的适当使用增加，并且可能与高成功率相关。对于像克雷伯氏菌属等物种，特别是 MDR 菌株，如果没有临床折点，可能会减少口服磷霉素的使用，特别是如果没有最低抑菌浓度。为了解决这个问题，本综述介绍了 FT 的临床前活性的概述，以及 FT 在女性单纯性下尿路感染和前列腺活检后预防感染性并发症中的临床活性的系统评价。研究结果表明，FT 单次口服剂量的安全性以及微生物学和临床疗效与具有更长治疗方案的比较方案相似，对于前列腺活检中的抗菌预防，FT 可以被认为是氟喹诺酮类药物的可行替代品。这些观察结果和广泛的临床经验支持了 FT 治疗 uUTI 的经验性使用，并表明 FT 是一种有效的候选药物，可以有效地对抗整个欧洲的抗生素耐药性 uUTI。
