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新型抗生素乐伐莫林单独及与多西环素联合使用对……的试验

test of the novel antibiotic lefamulin alone and in combination with doxycycline against .

作者信息

Salado-Rasmussen Kirsten, Nørgaard Christina, Pedersen Thomas Roland, Paukner Susanne, Jensen Jørgen Skov

机构信息

Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.

Department of Dermato-Venereology, Bispebjerg University Hospital, Copenhagen, Denmark.

出版信息

Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0134624. doi: 10.1128/aac.01346-24. Epub 2024 Dec 13.

DOI:10.1128/aac.01346-24
PMID:39670749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11784443/
Abstract

, a sexually transmitted bacterium, is a significant cause of urethritis in men and various reproductive tract infections in women, including cervicitis, pelvic inflammatory disease, endometritis, and potentially infertility. Treatment has become increasingly challenging due to the emergence of resistance to both first-line (azithromycin) and second-line (moxifloxacin) antibiotics. The need for new treatment options is critical. This study evaluates the efficacy of the novel antibiotic lefamulin against 54 . isolates, including highly resistant variants. Additionally, the potential synergistic effects of combining lefamulin with doxycycline were assessed in eight selected isolates. Lefamulin exhibited strong antibacterial activity across all tested isolates, with minimal inhibitory concentrations (MICs) ranging from 0.0005 to 0.064 µg/mL. Minimal bactericidal concentrations ranged from 0.001 to 0.128 µg/mL and were equal to the MIC in 40 of 54 isolates and within two- and fourfold MIC in the rest of the isolates. Notably, lefamulin's MIC values were significantly lower than those of azithromycin, doxycycline, and moxifloxacin, underscoring its potent efficacy. Checkerboard assays revealed no antagonistic interaction between lefamulin and doxycycline, with some additive effects observed in certain isolates. These findings highlight lefamulin's potential as a highly effective treatment for infections, particularly those involving multi-drug-resistant strains. Given the increasing rates of resistance and the limitations of current therapies, lefamulin may represent a promising new option for managing this challenging pathogen. Further clinical studies are warranted to confirm these results and explore the therapeutic potential of lefamulin in combination with doxycycline.

摘要

淋病奈瑟菌是一种性传播细菌,是男性尿道炎以及女性各种生殖道感染(包括宫颈炎、盆腔炎、子宫内膜炎,甚至可能导致不孕)的重要病因。由于对一线抗生素(阿奇霉素)和二线抗生素(莫西沙星)均出现耐药性,治疗变得越来越具有挑战性。因此,急需新的治疗方案。本研究评估了新型抗生素来法莫林对54株淋病奈瑟菌分离株(包括高度耐药变体)的疗效。此外,还在8株选定的分离株中评估了来法莫林与多西环素联合使用的潜在协同效应。来法莫林对所有测试分离株均表现出强大的抗菌活性,最低抑菌浓度(MIC)范围为0.0005至0.064μg/mL。最低杀菌浓度范围为0.001至0.128μg/mL,在54株分离株中有40株等于MIC,其余分离株的最低杀菌浓度在MIC的2倍和4倍之内。值得注意的是,来法莫林的MIC值显著低于阿奇霉素、多西环素和莫西沙星,突出了其强大的疗效。棋盘法试验显示来法莫林与多西环素之间无拮抗相互作用,在某些分离株中观察到一些相加效应。这些发现突出了来法莫林作为淋病感染(特别是涉及多重耐药菌株的感染)高效治疗药物的潜力。鉴于耐药率不断上升以及当前疗法的局限性,来法莫林可能是应对这种具有挑战性的病原体的一种有前景的新选择。有必要进行进一步的临床研究以证实这些结果,并探索来法莫林与多西环素联合使用的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b44/11784443/0c393483835b/aac.01346-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b44/11784443/0c393483835b/aac.01346-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b44/11784443/0c393483835b/aac.01346-24.f001.jpg

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2
Pharmacodynamic evaluation of lefamulin in the treatment of gonorrhea using a hollow fiber infection model simulating infections.使用模拟感染的中空纤维感染模型对来法莫林治疗淋病进行药效学评价。
Front Pharmacol. 2022 Nov 14;13:1035841. doi: 10.3389/fphar.2022.1035841. eCollection 2022.
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Phenotypic and genotypic antimicrobial susceptibility patterns of the emerging human respiratory pathogen Mycoplasma amphoriforme isolated from the UK and Denmark.从英国和丹麦分离出的新兴人类呼吸道病原体弯曲菌属的表型和基因型抗菌药物敏感性模式。
J Antimicrob Chemother. 2022 Oct 28;77(11):3126-3129. doi: 10.1093/jac/dkac293.
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