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杀菌性与抑菌性抗菌药物:临床意义、差异及临床实践中的协同潜力

Bactericidal versus bacteriostatic antibacterials: clinical significance, differences and synergistic potential in clinical practice.

作者信息

Ishak Angela, Mazonakis Nikolaos, Spernovasilis Nikolaos, Akinosoglou Karolina, Tsioutis Constantinos

机构信息

Department of Internal Medicine, 48202 Henry Ford Hospital, Detroit, MI, USA.

Department of Internal Medicine, Thoracic Diseases General Hospital Sotiria, 11527 Athens, Greece.

出版信息

J Antimicrob Chemother. 2025 Jan 3;80(1):1-17. doi: 10.1093/jac/dkae380.

Abstract

Antibacterial activity can be classified as either bactericidal or bacteriostatic, using methods such as the MBC/MIC ratio and time-kill curves. However, such categorization has proven challenging in clinical practice, as these definitions only apply under specific laboratory conditions, which may differ from clinical settings. Several factors, such as the specific bacteria or infectious medium, can affect the action of antibiotics, with many antibacterials exerting both activities. These definitions have also led to the belief that bactericidal antibacterials are superior to bacteriostatic, especially in more severe cases, such as endocarditis, neutropenia and bacteraemia. Additionally, current dogma dictates against the combination of bactericidal and bacteriostatic antibacterials in clinical practice, due to potential antagonism. This review aimed to assess the differences in antibacterial activity of bactericidal and bacteriostatic antibacterials based on in vitro and in vivo studies and examine their antagonistic or synergistic effects. Our findings show that specific bacteriostatic agents, such as linezolid and tigecycline, are clinically non-inferior to bactericidals in multiple infections, including pneumonia, intra-abdominal infections, and skin and soft tissue infections. Studies also support using several bacteriostatic agents as salvage therapies in severe infections, such as neutropenic fever and endocarditis. Additionally, not all combinations of bacteriostatic and bactericidal agents appear to be antagonistic, with many combinations, such as linezolid and rifampicin, already being used. The findings should be interpreted with caution, as most evidence is from observational studies and there is a need for randomized controlled trials to assess their effectiveness and combinations, especially within the context of rising antimicrobial resistance.

摘要

抗菌活性可分为杀菌性或抑菌性,可使用诸如MBC/MIC比值和时间-杀菌曲线等方法来分类。然而,在临床实践中,这种分类已被证明具有挑战性,因为这些定义仅适用于特定的实验室条件,而这些条件可能与临床环境不同。几个因素,如特定的细菌或感染介质,可影响抗生素的作用,许多抗菌药物同时具有这两种活性。这些定义还导致了一种观念,即杀菌性抗菌药物优于抑菌性抗菌药物,尤其是在更严重的病例中,如心内膜炎、中性粒细胞减少症和菌血症。此外,目前的教条规定在临床实践中反对将杀菌性和抑菌性抗菌药物联合使用,因为可能存在拮抗作用。本综述旨在基于体外和体内研究评估杀菌性和抑菌性抗菌药物的抗菌活性差异,并研究它们的拮抗或协同作用。我们的研究结果表明,特定的抑菌剂,如利奈唑胺和替加环素,在包括肺炎、腹腔内感染以及皮肤和软组织感染在内的多种感染中,在临床上并不亚于杀菌性药物。研究还支持在严重感染中,如中性粒细胞减少性发热和心内膜炎,使用几种抑菌剂作为挽救疗法。此外,并非所有抑菌剂和杀菌性药物的组合似乎都具有拮抗作用,许多组合,如利奈唑胺和利福平,已经在使用。这些研究结果应谨慎解读,因为大多数证据来自观察性研究,需要进行随机对照试验来评估它们的有效性和组合情况,尤其是在抗菌药物耐药性不断上升的背景下。

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