Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Emergency Medicine, Department of Emergency Medicine and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
J Glob Antimicrob Resist. 2020 Dec;23:388-393. doi: 10.1016/j.jgar.2020.10.017. Epub 2020 Nov 15.
To determine the minimum inhibitory concentration (MIC) distribution, epidemiological cut-off (ECOFF) values and clinical breakpoints (CBPs) of nemonoxacin, a non-fluorinated quinolone, for community-acquired pneumonia (CAP)-related Streptococcus pneumoniae and Staphylococcus aureus.
We pooled the susceptibility and clinical data of CAP patients enrolled in five clinical trials conducted in three countries from 2006 to 2017. Published pharmacokinetic (PK) profiles of oral (500 mg) and intravenous (IV) (500, 650 and 750 mg) nemonoxacin formulations and pharmacodynamic (PD) parameters of the two aforementioned CAP-related Gram-positive cocci (GPC) were used to determine plausible CBPs. Moreover, nemonoxacin MIC distributions of CAP-relatedS. pneumoniae (n = 1800) and S. aureus (n = 2000) isolates were obtained to evaluate ECOFF values using a visual estimation approach and ECOFFinder.
More than 92% of patients with CAP caused byS. pneumoniae or S. aureus with nemonoxacin MICs ≤ 0.25 mg/L presented positive clinical and microbiological outcomes. The ECOFF, MIC and MIC values of nemonoxacin were, respectively, 0.06, 0.125 and 1 mg/L for S. pneumoniae and 0.125, 1 and 8 mg/L for S. aureus. Based on differences in the PK profiles of oral and IV formulations, PD parameters of nemonoxacin for these CAP-GPC and clinical in vivo efficacy data, tentative CBPs of 0.5, 0.5 and 1 mg/L, respectively, were established for the 500 mg oral and 500 mg and 750 mg IV nemonoxacin formulations for S. pneumoniae, and 0.25, 0.5 and 1 mg/L for S. aureus.
This study provides plausible nemonoxacin CBPs for two important CAP-GPC.
确定非氟喹诺酮类药物奈莫沙星对社区获得性肺炎（CAP）相关肺炎链球菌和金黄色葡萄球菌的最低抑菌浓度（MIC）分布、流行病学折点（ECOFF）值和临床断点（CBP）。
我们汇总了 2006 年至 2017 年在三个国家进行的五项临床试验中 CAP 患者的药敏和临床数据。使用口服（500mg）和静脉（IV）（500、650 和 750mg）奈莫沙星制剂的已发表药代动力学（PK）曲线和上述两种 CAP 相关革兰阳性球菌（GPC）的药效动力学（PD）参数来确定合理的 CBP。此外，我们还获得了奈莫沙星治疗 CAP 相关肺炎链球菌（n=1800）和金黄色葡萄球菌（n=2000）分离株的 MIC 分布，以通过视觉评估方法和 ECOFFinder 评估 ECOFF 值。
超过 92%的 CAP 患者，其肺炎链球菌或金黄色葡萄球菌的奈莫沙星 MIC 值≤0.25mg/L，临床和微生物学结果均为阳性。奈莫沙星的 ECOFF、MIC 和 MIC 值分别为 0.06、0.125 和 1mg/L，用于肺炎链球菌，0.125、1 和 8mg/L，用于金黄色葡萄球菌。基于口服和 IV 制剂 PK 曲线的差异、奈莫沙星对这些 CAP-GPC 的 PD 参数以及临床体内疗效数据，我们分别为 500mg 口服和 500mg 和 750mg IV 奈莫沙星制剂建立了暂定的 CBP，用于肺炎链球菌为 0.5、0.5 和 1mg/L，用于金黄色葡萄球菌为 0.25、0.5 和 1mg/L。
本研究为两种重要的 CAP-GPC 提供了合理的奈莫沙星 CBP。
