Craddock Vaughn D, Steere Evan L, Harman Hannah, Britt Nicholas S
Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, KS 66047, USA.
Department of Population Health, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Antibiotics (Basel). 2023 Jun 20;12(6):1078. doi: 10.3390/antibiotics12061078.
Delafloxacin (DLX) is a recently approved fluoroquinolone with broad activity against common cystic fibrosis (CF) pathogens, including multidrug-resistant (MDR-Psa). Delafloxacin has been previously shown to have excellent lung and biofilm penetration and enhanced activity at lower pH environments, such as those that would be observed in the CF lung. We analyzed six Psa strains isolated from CF sputum and compared DLX to ciprofloxacin (CPX) and levofloxacin (LVX). Minimum inhibitory concentrations (MICs) were determined for DLX using standard culture media (pH 7.3) and artificial sputum media (ASM), a physiologic media recapitulating the CF lung microenvironment (pH 6.9). Delafloxacin activity was further compared to CPX and LVX in an in vitro CF sputum time-kill model at physiologically relevant drug concentrations (Cmax, Cmed, Cmin). Delafloxacin exhibited 2- to 4-fold MIC reductions in ASM, which corresponded with significant improvements in bacterial killing in the CF sputum time-kill model between DLX and LVX at Cmed ( = 0.033) and Cmin ( = 0.004). Compared to CPX, DLX demonstrated significantly greater killing at Cmin ( = 0.024). Overall, DLX demonstrated favorable in vitro activity compared to alternative fluoroquinolones against MDR-Psa. Delafloxacin may be considered as an option against MDR-Psa pulmonary infections in CF.
德拉氟沙星（DLX）是一种最近获批的氟喹诺酮类药物，对常见的囊性纤维化（CF）病原体具有广泛活性，包括多重耐药性铜绿假单胞菌（MDR-Psa）。此前已证明德拉氟沙星具有出色的肺部和生物膜穿透力，并且在较低pH环境（如CF肺部所观察到的环境）中活性增强。我们分析了从CF痰液中分离出的6株铜绿假单胞菌菌株，并将德拉氟沙星与环丙沙星（CPX）和左氧氟沙星（LVX）进行比较。使用标准培养基（pH 7.3）和人工痰液培养基（ASM，一种模拟CF肺部微环境的生理培养基，pH 6.9）测定德拉氟沙星的最低抑菌浓度（MIC）。在体外CF痰液时间-杀菌模型中，在生理相关药物浓度（Cmax、Cmed、Cmin）下，进一步将德拉氟沙星的活性与环丙沙星和左氧氟沙星进行比较。德拉氟沙星在ASM中的MIC降低了2至4倍，这与在Cmed（P = 0.033）和Cmin（P = 0.004）时，德拉氟沙星和左氧氟沙星在CF痰液时间-杀菌模型中细菌杀灭的显著改善相对应。与环丙沙星相比，德拉氟沙星在Cmin时显示出显著更强的杀菌效果（P = 0.024）。总体而言，与其他氟喹诺酮类药物相比，德拉氟沙星对MDR-Psa显示出良好的体外活性。德拉氟沙星可被视为治疗CF中MDR-Psa肺部感染的一种选择。
