预测头孢曲松在淋病治疗中的使用限制:即将出现的耐药性和后勤挑战。

IF 4.2 2区 医学 Q1 INFECTIOUS DISEASES
Susannah F Vanderpool, Nardine Karam, Margaret R Hammerschlag
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引用次数: 0

摘要

淋病奈瑟菌中抗菌素耐药性的日益流行威胁到头孢曲松的疗效,头孢曲松是最后一种广泛有效的淋病治疗药物。耐药机制挑战了当前给药策略的充分性和最低抑制浓度(MIC)阈值,MIC低至0.125 mcg/mL时治疗失败。有限的临床和药效学数据使确定最佳剂量和耐药断点的努力复杂化。涵盖领域:本综述研究了头孢曲松推荐剂量随耐药趋势的演变,探讨了导致易感性降低的遗传和药代动力学因素,并严格评估了CDC的MIC“警戒值”0.125微克/毫升。监测数据与药代动力学/药效学(PK/PD)模型一起进行分析,包括蒙特卡罗模拟和中空纤维感染模型(HFIM)。实际的挑战,包括注射部位耐受性,利多卡因的安全性和剂量限制的肌肉注射,进行了审查。专家意见:目前的PK/PD数据和静脉耐受性研究支持头孢曲松剂量递增至3.5 g IM作为mic高达0.5 mcg/mL菌株的可行门诊限制。然而,即使是高剂量治疗方案也无法达到的最低剂量仍是未知的。当务之急包括通过临床药代动力学和结局研究验证更高的剂量,根据解剖部位改进MIC阈值,以及评估可靠的咽部根除新药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Predicting the limit to ceftriaxone's use in gonorrhea treatment: impending resistance and logistical challenges.

Introduction: The increasing prevalence of antimicrobial resistance in Neisseria gonorrhoeae threatens the efficacy of ceftriaxone, the last widely effective treatment for gonorrhea. Resistance mechanisms challenge the adequacy of current dosing strategies and minimum inhibitory concentration (MIC) thresholds, with treatment failures documented at MICs as low as 0.125 mcg/mL. Limited clinical and pharmacodynamic data complicate efforts to define optimal dosing and resistance breakpoints.

Areas covered: This review examines the evolution of ceftriaxone dosing recommendations in response to resistance trends, explores the genetic and pharmacokinetic factors driving reduced susceptibility, and critically evaluates the CDC's MIC 'alert value' of 0.125 mcg/mL. Surveillance data are analyzed alongside pharmacokinetic/pharmacodynamic (PK/PD) models, including Monte Carlo simulations and hollow fiber infection models (HFIM). Practical challenges, including injection site tolerability, lidocaine safety, and dosing limits for intramuscular administration, are reviewed.

Expert opinion: Current PK/PD data and IV tolerability studies support ceftriaxone dose escalation up to 3.5 g IM as a feasible outpatient limit for strains with MICs up to 0.5 mcg/mL. However, the MIC at which even high-dose regimens fail remains unknown. Urgent priorities include validating higher doses through clinical pharmacokinetic and outcomes studies, refining MIC thresholds by anatomical site, and evaluating novel agents for reliable pharyngeal eradication.

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来源期刊
CiteScore
11.20
自引率
0.00%
发文量
66
审稿时长
4-8 weeks
期刊介绍: Expert Review of Anti-Infective Therapy (ISSN 1478-7210) provides expert reviews on therapeutics and diagnostics in the treatment of infectious disease. Coverage includes antibiotics, drug resistance, drug therapy, infectious disease medicine, antibacterial, antimicrobial, antifungal and antiviral approaches, and diagnostic tests.
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