新一代氟喹诺酮类药物司帕沙星有可能克服多数耐药性 . 中左氧氟沙星和莫西沙星的耐药性。
New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant .
机构信息
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, PR China.
Pharmacy of Beijing Chest Hospital, Capital Medical University, Beijing, PR China.
出版信息
J Med Microbiol. 2024 Jul;73(7). doi: 10.1099/jmm.0.001825.
Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ. Sfx is more active against drug-resistant (Mtb) isolates. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC of 0.0313 µg ml and MIC of 0.125 µg ml, which was lower than that of Mfx (MIC = 0.0625 µg ml, MIC = 1 µg ml) and Lfx (MIC = 0.125 µg ml, MIC = 2 µg ml). We determined the tentative epidemiological cut-off values as 0.5 µg ml for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in or , 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.
先前存在的氟喹诺酮（FQs）耐药性是治疗多药耐药（MDR）结核病的主要威胁。司氟沙星（Sfx）是一种新型的广谱 FQ。Sfx 对耐药性（Mtb）分离株更具活性。为了确定 MDR Mtb 中 Sfx 与氧氟沙星（Ofx）、左氧氟沙星（Lfx）和莫西沙星（Mfx）之间是否存在交叉耐药性。总共分析了 106 株临床 Mtb 分离株，包括 23 株全敏感株和 83 株 MDR 株，采用 MIC 测定法测定 Sfx、Lfx 和 Mfx 耐药性。还对分离株进行了全基因组测序，以分析耐药基因。Sfx 对 Mtb 临床分离株表现出最强大的抑制活性，MIC 为 0.0313 µg ml，MIC 为 0.125 µg ml，低于 Mfx（MIC = 0.0625 µg ml，MIC = 1 µg ml）和 Lfx（MIC = 0.125 µg ml，MIC = 2 µg ml）。我们确定暂定的流行病学截断值为 0.5 µg ml。此外，8.43%（7/83）、43.37%（36/83）、42.17%（35/83）和 51.81%（43/83）的 MDR 株分别对 Sfx、Mfx、Lfx 和 Ofx 耐药。Ofx、Lfx 和 Mfx 之间存在交叉耐药性，为 80.43%（37/46）。仅有 15.22%（7/46）的先前存在的 FQs 耐药分离株对 Sfx 耐药。在 30 株存在 或 基因突变的分离株中，有 5 株（16.67%）对 Sfx 耐药。Sfx 与利福平联合使用可发挥部分协同作用，并且 Sfx 与六种临床重要的抗 Mtb 抗生素之间没有明显的拮抗作用。Sfx 对 MDR 分离株的活性优于 Lfx 和 Mfx，并且有可能克服 Mtb 菌株中大多数先前存在的 FQs 耐药性。
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