胆汁中头孢他啶和阿维菌素的浓度--一项前瞻性 IIb 期研究。

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Journal of Antimicrobial Chemotherapy Pub Date : 2024-10-07 DOI:10.1093/jac/dkae361
Andrea Witowski, Lars Palmowski, Iris K Minichmayr, Markus Zeitlinger, Christoph Dorn, Constantin Lier, Michael Adamzik, Hartmuth Nowak, Tim Rahmel
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引用次数: 0

摘要

背景:耐碳青霉烯类细菌的增加和有效抗生素的有限数量对医疗保健构成了重大威胁。头孢他啶(CAZ)和阿维巴坦(AVI)的联合用药已被批准用于治疗耐碳青霉烯类药物的腹腔感染。然而,目前尚缺乏 AVI 在肝胆区的药代动力学特征数据:目的:提供AVI在胆汁液中的浓度作为肝胆排泄替代物的临床活体数据:在这项 IIb 期研究(DRKS-ID:DRKS00023533)中,有 9 名患者获得了胆汁样本。研究测定了血浆(0-8 小时)、胆汁(切除术后)中的抗生素浓度和药效学参数:CAZ和AVI在胆汁中的平均浓度分别为33.5毫克/升(±20.5毫克/升)和7.1毫克/升(±3.5毫克/升),胆汁/血浆比分别为0.58(±0.26)和0.61(±0.18)。CAZ在血浆中的最大浓度为87.2毫克/升(±25.0毫克/升),AVI为18.6毫克/升(±6.29毫克/升),AUC0-∞值分别为351小时-毫克/升(±104小时-毫克/升)和72.1小时-毫克/升(±32.1小时-毫克/升)。所有患者的CAZ和AVI血浆浓度在给药间隔期内均高于最低抑制浓度的50%以上(T>MIC > 50%;MICCAZ = 8 mg/L,MICAVI = 1 mg/L)。在30天的随访过程中,没有出现与抗生素相关的副作用:结论:CAZ和AVI在胆汁中的浓度表明,它们有可能成为治疗多重耐药性胆道感染的重要选择。
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Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study.

Background: The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking.

Objectives: To provide clinical in vivo data on the concentration of AVI in bile fluid as a surrogate for hepatobiliary excretion.

Methods: A single dose of 2000/500 mg CAZ/AVI was administered prolonged over 2 h to 10 patients prior to abdominal surgery, with bile samples available in nine patients in this phase IIb study (DRKS-ID: DRKS00023533). Antibiotic concentrations in plasma (0-8 h), bile (after resection) and pharmacodynamic parameters were determined.

Results: The mean concentration across individuals in bile was 33.5 mg/L (±20.5 mg/L) for CAZ and 7.1 mg/L (±3.5 mg/L) for AVI, resulting in bile/plasma ratios of 0.58 (±0.26) and 0.61 (±0.18). The Cmax in plasma was 87.2 mg/L (±25.0 mg/L) for CAZ and 18.6 mg/L (±6.29 mg/L) for AVI, with AUC0-∞ values of 351 h·mg/L (±104 h·mg/L) and 72.1 h·mg/L (±32.1 h·mg/L), respectively. Plasma concentrations of both CAZ and AVI remained more than 50% of the dosing interval above the minimum inhibitory concentrations (T>MIC > 50%; MICCAZ = 8 mg/L, MICAVI = 1 mg/L) in all patients. No antibiotic-associated side effects were reported during the 30-day follow-up.

Conclusions: The concentrations of CAZ and AVI in bile suggest their potential as a valuable therapeutic option for multi-resistant biliary infections.

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来源期刊
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.
期刊最新文献
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