Pharmacodynamics Of Linezolid-Plus-Fosfomycin Against Vancomycin-Susceptible And -Resistant Enterococci In Vitro And In Vivo Of A Galleria mellonella Larval Infection Model

Qi C, Xu S, Wu M, Zhu S, Liu Y, Huang H, Zhang G, Li J, Huang X
2019 Infection and Drug Resistance  
Caifen Qi,1,2,* Shuangli Xu,1,* Maomao Wu,1 Shuo Zhu,1 Yanyan Liu,3 Hong Huang,1 Guijun Zhang,1 Jiabin Li,3 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People's Republic of China; 2Department of Pharmacy, The Anqing Affiliated Hospital of Anhui Medical University, Anqing, Anhui, People's Republic of China; 3Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui,
more » ... le's Republic of China*These authors contributed equally to this workCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Meishan Road 81#, Hefei, Anhui 230032, People's Republic of ChinaTel +86 138 5518 3138Email math2088@163.com Jiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218#, Hefei, Anhui, People's Republic of ChinaFax +86551 62922713Email lijiabin@ahmu.edu.cnObjectives: To explore the in vitro and in vivo antibacterial activity of linezolid/fosfomycin combination against vancomycin-susceptible and -resistant enterococci (VSE and VRE), and provide a theoretical basis for the treatment of VRE.Methods: The checkerboard method and time-kill curve study were used to evaluate the efficacy of linezolid combined with fosfomycin against VSE and VRE. The transmission electron microscopy (TEM) was employed to observe the cell morphology of bacteria treated with each drug alone or in combination, which further elucidate the mechanism of action of antibiotic combination therapy. The Galleria mellonella infection model was constructed to demonstrate the in vivo efficacy of linezolid plus fosfomycin for VSE and VRE infection.Results: The fractional inhibitory concentration index (FICI) values of all strains suggested that linezolid showed synergy or additivity in combination with fosfomycin against five of the six strains. Time-kill experiments demonstrated that the combination of linezolid-fosfom [...]
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