Shujuan Ji1,2, Shengnan Jiang1,2, Xiang Wei1,2, Lu Sun1,2, Haiping Wang1,2, Feng Zhao3, Yan Chen1,2, Yunsong Yu1,2. 1. Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2. Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China. 3. Department of Clinical laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
BACKGROUND: Daptomycin is considered an important alternative for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). However, treatment failures associated with daptomycin nonsusceptibility isolates have been reported in recent years. METHODS: In this study, we investigated serial MRSA strains from 3 endocarditis patients who had breakthrough bacteremia, despite treatment with daptomycin. The strains were analyzed by whole-genome sequencing, molecular typing, and mutation screening. Population analysis and growth curves were also applied to evaluate heteroresistance and fitness cost. RESULTS: This series of MRSA strains belonged to ST5, ST59, and ST4513. The daptomycin minimum inhibitory concentrations for these MRSA strains increased after daptomycin exposure, whereas daptomycin-resistant strains emerged with mutations in mprF and yycH. Population analysis profiling results demonstrated the presence of a daptomycin-heteroresistant subpopulation among daptomycin-susceptible MRSA strains, and no significant fitness cost was observed within these heteroresistant MRSA clones. CONCLUSIONS: We confirmed that daptomycin heteroresistance and resistance could emerge rapidly in MRSA strains of different lineages after daptomycin exposure. Further studies to fully understand the mechanism(s) underlying daptomycin resistance in MRSA are required.
BACKGROUND:Daptomycin is considered an important alternative for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). However, treatment failures associated with daptomycin nonsusceptibility isolates have been reported in recent years. METHODS: In this study, we investigated serial MRSA strains from 3 endocarditispatients who had breakthrough bacteremia, despite treatment with daptomycin. The strains were analyzed by whole-genome sequencing, molecular typing, and mutation screening. Population analysis and growth curves were also applied to evaluate heteroresistance and fitness cost. RESULTS: This series of MRSA strains belonged to ST5, ST59, and ST4513. The daptomycin minimum inhibitory concentrations for these MRSA strains increased after daptomycin exposure, whereas daptomycin-resistant strains emerged with mutations in mprF and yycH. Population analysis profiling results demonstrated the presence of a daptomycin-heteroresistant subpopulation among daptomycin-susceptible MRSA strains, and no significant fitness cost was observed within these heteroresistant MRSA clones. CONCLUSIONS: We confirmed that daptomycin heteroresistance and resistance could emerge rapidly in MRSA strains of different lineages after daptomycin exposure. Further studies to fully understand the mechanism(s) underlying daptomycin resistance in MRSA are required.
Authors: Stefano G Giulieri; Romain Guérillot; Sebastian Duchene; Abderrahman Hachani; Diane Daniel; Torsten Seemann; Joshua S Davis; Steven Y C Tong; Bernadette C Young; Daniel J Wilson; Timothy P Stinear; Benjamin P Howden Journal: Elife Date: 2022-06-14 Impact factor: 8.713