Identification of Persister Drug Combination Clinafloxacin+Cefuroxime+Gentamicin That Eradicates Persistent Pseudomonas aeruginosa Infection in a Murine Cystic Fibrosis Model  

作　　者：Yuting Yuan Rebecca Yee Naina Gour Xinzhong Dong Jie Feng Wanliang Shi Ying Zhang 

机构地区：[1]Department of Molecular Microbiology and Immunology,Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,USA [2]The Solomon H.Snyder Department of Neuroscience and the Center for Sensory Biology,Johns Hopkins University School of Medicine,Baltimore,Maryland,USA [3]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,National Medical Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China [4]Research Units of Infectious Disease and Microecology,Chinese Academy of Medical Sciences,Hangzhou,Zhejiang,China [5]Jinan Microecological Biomedicine Shandong Laboratory,Jinan,Shandong,China

出　　处：《Infectious Microbes & Diseases》2023年第1期21-28,共8页感染微生物与疾病（英文）

摘　　要：Pseudomonas aeruginosa can cause persistent infections,such as biofilm infections,in cystic fibrosis patients,which are difficult to cure due to non-growing persister bacteria that are not effectively killed by the current treatments.While antibiotic activity against growing P.aeruginosa is well documented,their activity against non-growing stationary phase cultures is less clear.Here,we evaluated six major classes of antibiotics,including cell wall and cell membrane inhibitors,protein synthesis inhibitors,DNA synthesis inhibitors,RNA synthesis inhibitors,sulfa drugs and nitrofurantoin,for their activity against growing and non-growing P.aeruginosa.We foundthat cell wall and cell membrane inhibitors(cefuroxime and colistin),DNA synthesis inhibitors(clinafloxacin)and sulfa drugs(sulfamethoxazole)had good activity against stationary-phase bacteria,while protein synthesis inhibitors(gentamicin),RNA synthesis inhibitor(rifampin)and nitrofurantoin showed relatively poor activity.Clinafloxacin was the only drug able to completely eradicate stationary-phase bacteria within four days.The cefuroxime+gentamicin+clinafloxacin combination was able to kill all bacteria from a biofilm within two days,whereas the clinically used drug combination cefuroxime+gentamicin/colistin only partially killed the biofilmbacteria.In amurine persistent cystic fibrosis lung infectionmodel,only the cefuroxime+gentamicin+clinafloxacin drug combination eradicated all bacteria from the lungs,whereas clinafloxacin alone,cefuroxime+clinafloxacin or the currently recommended drug combination cefuroxime+gentamicin failed to do so.The complete eradication is a property of the clinafloxacin combination,as the otherwise identical levofloxacin combination did not clear the bacterial loads from the lungs.Our findings offer new therapeutic options for more effective treatment of persistent P.aeruginosa infections,with possible implications for treating other persistent infections.

关 键 词：Pseudomonas aeruginosa persisters stationary-phase bacteria BIOFILM CLINAFLOXACIN cystic fibrosis 

分 类 号：R28[医药卫生—中药学]