评价感染性心内膜炎患者心脏瓣膜组织中阿莫西林的扩散情况：一项前瞻性观察性非对照研究。

Evaluating the heart valve tissue diffusion of amoxicillin in infective endocarditis: a pilot prospective observational non-comparative study.

机构信息

Mobile Infectiology Unit, Microbiology Department, European Hospital Georges Pompidou, AP-HP Paris Cité University, Paris, France.

Pharmacology Department, European Hospital Georges Pompidou, AP-HP Paris Cité University, Paris, France.

出版信息

J Antimicrob Chemother. 2023 Dec 1;78(12):2915-2918. doi: 10.1093/jac/dkad330.

DOI:10.1093/jac/dkad330

PMID:37878769

Abstract

OBJECTIVES

Treating patients with infective endocarditis (IE) due to streptococci and enterococci currently involves high-dosage antibiotics. Recent literature suggests a 30%-70% diffusion rate could be extrapolated to human heart valve tissue. The objective of this study was to evaluate the diffusion coefficient of amoxicillin in heart valve tissue of patients operated for IE.

METHODS

Adult patients were prospectively included that underwent surgery at the European Hospital Georges Pompidou for IE due to streptococci and enterococci and had previous IV amoxicillin treatment. Plasma (taken 48 h preoperatively) and heart valve tissue amoxicillin concentrations were measured with a validated LC-MS/MS method. The MIC values of amoxicillin were measured for all available isolates.

RESULTS

Seventeen patients were included. Eleven (64.7%) patients had native valve IE and six (35.3%) had prosthetic valve IE. Fourteen IE cases (82.4%) were due to streptococci, one (5.9%) was due to enterococci and two (11.8%) were Haemophilus spp, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae group infections. Median (IQR) amoxicillin dose administered was 10.5 (8.0-12.0) g/day corresponding to 138.2 (112.5-160.0) mg/kg/day. The median amoxicillin plasma concentrations pre-surgery and intra-tissular weighted concentrations were 31.9 (25.9-51.9) mg/L and 19.0 (7.9-31.4) µg/g, respectively. Median tissue/plasma concentration ratio was 0.47 (0.24-0.67), with a median amoxicillin plasma/MIC ratio of 487 (179-745), and median amoxicillin tissue/MIC ratio of 42 (14-116).

CONCLUSIONS

With a significant diffusion coefficient, amoxicillin dosage in heart valve tissues showed a concentration/MIC ratio well above current recommendations for bactericidal activity. Our study suggests that lower doses can be considered for susceptible bacteria.

摘要

目的

治疗由链球菌和肠球菌引起的感染性心内膜炎（IE）患者目前需要使用高剂量抗生素。最近的文献表明，扩散率为 30%-70%可外推至人类心脏瓣膜组织。本研究的目的是评估 IE 患者心脏瓣膜组织中阿莫西林的扩散系数。

方法

前瞻性纳入在欧洲 Georges Pompidou 医院因链球菌和肠球菌引起 IE 并接受过 IV 阿莫西林治疗的成年患者。使用经过验证的 LC-MS/MS 方法测量术前 48 小时采集的血浆和心脏瓣膜组织中的阿莫西林浓度。测量所有可用分离株的阿莫西林 MIC 值。

结果

共纳入 17 例患者。11 例（64.7%）患者为原发性瓣膜 IE，6 例（35.3%）为人工瓣膜 IE。14 例 IE 病例（82.4%）由链球菌引起，1 例（5.9%）由肠球菌引起，2 例（11.8%）由嗜血杆菌属、伴放线放线杆菌、心杆菌属、腐生真杆菌、金氏金杆菌群感染引起。中位（IQR）剂量为 10.5（8.0-12.0）g/天，相当于 138.2（112.5-160.0）mg/kg/天。术前中位阿莫西林血浆浓度和组织加权浓度分别为 31.9（25.9-51.9）mg/L 和 19.0（7.9-31.4）µg/g。中位组织/血浆浓度比为 0.47（0.24-0.67），中位阿莫西林血浆/MIC 比值为 487（179-745），中位阿莫西林组织/MIC 比值为 42（14-116）。