环丙沙星在导管相关性尿路感染模型中的口服生物膜活性

Oral ciprofloxacin biofilm activity in a catheter-associated urinary tract infection model.

作者信息

Abbott Iain J, Anderson Connor R B, van Gorp Elke, Wallis Steve C, Roberts Jason A, Meletiadis Joseph, Peleg Anton Y

机构信息

Department of Infectious Diseases, Alfred Hospital and School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.

University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.

出版信息

J Antimicrob Chemother. 2025 Feb 3;80(2):413-426. doi: 10.1093/jac/dkae424.

DOI:10.1093/jac/dkae424

PMID:39626168

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11787899/

Abstract

BACKGROUND

Catheter-associated urinary tract infections (CA-UTIs) are a common hospital-acquired infection. We examined ciprofloxacin activity in a novel CA-UTI in vitro model.

METHODS

Three ATCC strains [Escherichia coli (ECO)-25922, Klebsiella pneumoniae (KPN)-700721, Pseudomonas aeruginosa (PAE)-27853] and 45 clinical urinary isolates were assessed. Biofilm mass and planktonic bacterial density were quantified during drug-free incubation (72 h) and following ciprofloxacin exposure (equivalent 750 mg orally q12h, 3 days).

RESULTS

ECO produced smaller biofilms (6.3 ± 1.1 log10 cfu/cm2) compared with KPN (7.1 ± 0.7 log10 cfu/cm2) and PAE (7.0 ± 1.2 log10 cfu/cm2), which extended along the entire catheter length. Following ciprofloxacin, all isolates with MIC > 4 mg/L had minimal biofilm disruption or planktonic kill. Ciprofloxacin resistance was most common in PAE isolates (10/16 isolates), compared with ECO (3/16 isolates) and KPN (6/16 isolates). Greater ciprofloxacin exposure (AUC0-24/MIC) was required for a 3 log10 biofilm kill for KPN (5858; R2 = 0.7774) compared with ECO (2117; R2 = 0.7907) and PAE (2485; R2 = 0.8260). Due to persistent growth in the bladder, ECO required greater ciprofloxacin exposure for a 3 log10 planktonic kill (5920; R2 = 0.8440) compared with KPN (2825; R2 = 0.9121) and PAE (1760; R2 = 0.8781). Monte Carlo simulation supported a 95% PTA for both a 3 log10 biofilm and planktonic kill for ECO and KPN isolates with MIC ≤ 0.5 mg/L and PAE isolates with MIC ≤ 1 mg/L.

CONCLUSIONS

In a novel CA-UTI model, following simulated ciprofloxacin therapy, KPN biofilms were comparatively more difficult to disrupt, ECO planktonic growth frequently persisted in the bladder, and PAE had greater propensity for emergence of ciprofloxacin resistance.

摘要

背景

导尿管相关尿路感染（CA-UTIs）是一种常见的医院获得性感染。我们在一种新型CA-UTI体外模型中检测了环丙沙星的活性。

方法

评估了三株美国典型培养物保藏中心（ATCC）菌株[大肠埃希菌（ECO）-25922、肺炎克雷伯菌（KPN）-700721、铜绿假单胞菌（PAE）-27853]和45株临床尿液分离株。在无药物孵育（72小时）期间以及环丙沙星暴露后（相当于口服750mg，每12小时一次，共3天），对生物膜量和浮游细菌密度进行了定量。

结果

与KPN（7.1±0.7 log10 cfu/cm²）和PAE（7.0±1.2 log10 cfu/cm²）相比，ECO产生的生物膜较小（6.3±1.1 log10 cfu/cm²），且沿整个导管长度延伸。环丙沙星治疗后，所有最低抑菌浓度（MIC）>4mg/L的分离株生物膜破坏或浮游菌杀灭作用最小。环丙沙星耐药在PAE分离株中最常见（10/16株），而ECO为（3/16株），KPN为（6/16株）。与ECO（2117；R²=0.7907）和PAE（2485；R²=0.8260）相比，KPN需要更高的环丙沙星暴露量（药时曲线下面积/最低抑菌浓度，AUC0-24/MIC）才能实现3 log10的生物膜杀灭（5858；R²=0.7774）。由于在膀胱中持续生长，与KPN（2825；R²=0.9121）和PAE（1760；R²=0.8781）相比，ECO需要更高的环丙沙星暴露量才能实现3 log10的浮游菌杀灭（5920；R²=0.8440）。蒙特卡洛模拟支持对于MIC≤0.5mg/L的ECO和KPN分离株以及MIC≤1mg/L的PAE分离株，实现3 log10生物膜和浮游菌杀灭的95%目标成功率（PTA）。