肝囊肿感染靶部位抗生素渗透：一项随机药代动力学试验。

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

作者信息

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

机构信息

Department of Gastroenterology and Hepatology, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.

Department of Medical Microbiology, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

J Antimicrob Chemother. 2025 Jan 3;80(1):182-191. doi: 10.1093/jac/dkae394.

DOI:10.1093/jac/dkae394

PMID:39508371

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11695873/

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.

摘要

背景

欧洲肝脏研究学会（EASL）肝囊肿疾病指南指出，药物在感染部位（肝囊肿）的渗透对于成功治疗至关重要，但关于囊肿渗透的药代动力学（PK）数据有限。

目的

本研究旨在调查四种抗生素在未感染肝囊肿中的组织渗透情况，并探索影响因素。

方法

我们进行了一项前瞻性、随机单剂量PK研究。在对未感染的肝囊肿进行经皮引流之前，静脉注射（IV）一剂环丙沙星和哌拉西林/他唑巴坦（第1组）；或复方新诺明（甲氧苄啶/磺胺甲恶唑）和强力霉素（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。使用经过验证的液相色谱-串联质谱法（LC-MS/MS）测量药物浓度。主要结局是肝囊肿渗透，定义为囊液与血浆浓度比（%），以中位数（四分位间距）表示。

结果

我们纳入了20例患者，共引流了21个肝囊肿（第1组：n = 11，第2组：n = 10）。引流的囊肿体积中位数为700 mL。输注与引流之间的时间中位数为139分钟（四分位间距120 - 188分钟）。环丙沙星的囊液与血浆浓度比中位数为4.2%（四分位间距1.6% - 8.9%），哌拉西林为0.3%（四分位间距0.0% - 1.3%），他唑巴坦为0.2%（四分位间距0.0% - 1.3%），甲氧苄啶为12.2%（四分位间距6.3% - 16.1%），磺胺甲恶唑为0.4%（四分位间距0.2% - 3.8%），强力霉素为1.6%（四分位间距0.9% - 2.3%）。甲氧苄啶输注与囊肿引流之间的时间与囊液与血浆浓度比增加相关（P < 0.01）。