Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial.

IF 3.9 2区医学 Q1 INFECTIOUS DISEASES

Journal of Antimicrobial Chemotherapy Pub Date : 2024-11-07 DOI:10.1093/jac/dkae394

Lucas H P Bernts, Roger J M Brüggemann, Anouk M E Jansen, Nynke G L Jager, Heiman F L Wertheim, Joost P H Drenth, Marten A Lantinga

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引用次数: 0

Abstract

Background: The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited.

Objectives: This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors.

Methods: We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR).

Results: We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120-188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%-8.9%) for ciprofloxacin, 0.3% (IQR 0.0%-1.3%) for piperacillin, 0.2% (IQR 0.0%-1.3%) for tazobactam, 12.2% (IQR 6.3%-16.1%) for trimethoprim, 0.4% (IQR 0.2%-3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%-2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01).

Conclusions: Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose.

Clinical trial number: NTR8499The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.

查看原文本刊更多论文

抗生素在感染目标部位的肝囊肿穿透：随机药代动力学试验。

背景：EASL囊性肝病指南指出，药物在感染部位（肝囊肿）的渗透是成功治疗的关键，但有关囊肿渗透的药代动力学（PK）数据有限：本研究旨在调查四种抗生素在非感染肝囊肿中的组织穿透性，并探讨影响因素：我们进行了一项前瞻性、随机单剂量 PK 研究。在对非感染性肝囊肿进行经皮引流前，静脉注射环丙沙星和哌拉西林/他唑巴坦（第1组），或联合曲唑（三甲双嘧/磺胺甲噁唑）和多西环素（第2组）。在引流过程中收集囊液。在引流前、引流期间和引流后（12 小时内）采集血样。药物浓度由经过验证的 LC-MS/MS 测定。主要结果是肝囊肿穿透率，定义为囊肿液与血浆浓度比值（%），以中位数（IQR）表示：我们共纳入了 20 名患者，引流了 21 个肝囊肿（第 1 组：n = 11，第 2 组：n = 10）。引流出的囊肿体积中位数为 700 毫升。从输液到引流的中位时间为 139 分钟（IQR 120-188 分钟）。环丙沙星的中位囊液血浆浓度比为 4.2%（IQR 1.6%-8.9%），哌拉西林的中位囊液血浆浓度比为 0.3%（IQR 0.0%-1.3%），他唑巴坦的中位囊液血浆浓度比为 0.2%（IQR 0.0%-1.3%）。他唑巴坦为 0.2%（IQR 0.0%-1.3%），三甲氧苄氨嘧啶为 12.2%（IQR 6.3%-16.1%），磺胺甲噁唑为 0.4%（IQR 0.2%-3.8%），强力霉素为 1.6%（IQR 0.9%-2.3%）。输注三甲氧苄啶与囊肿引流之间的时间与囊肿液与血浆浓度比值的增加相关（P 结论：囊肿引流时间与囊肿液与血浆浓度比值的增加相关：在测试的抗生素中，曲美普林和环丙沙星的渗透率最高。我们发现，不同药物在单次静脉注射后的肝囊肿穿透性差异很大：NTR8499该试验最初在荷兰试验注册中心（ID：NL7290）注册，并于2022年转入国际临床试验注册平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Antimicrobial Chemotherapy 医学-传染病学

CiteScore

9.20

自引率

5.80%

发文量

423

审稿时长

2-4 weeks

期刊介绍： The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.