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Published on: April 18, 2019
In vitro Antimicrobial Activity of Fosfomycin, Rifampin, Vancomycin, Daptomycin Alone and in Combination Against
Jiepeng Tong1, Yiheng Jiang2, Hao Xu1
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Purpose:
The emergence of vancomycin resistant Enterococci (VRE) is shortening the choices for clinical anti-infective therapy. The aim of this study was to investigate the mechanism of vancomycin resistance and evaluate the effect of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), daptomycin (DAP) alone or in combination against VRE.
Methods:
Eight VRE isolates were collected. A total of 18 antibiotics susceptibility tests were further done for VRE. Whole genome sequencing and bioinformatics analysis were performed. The effect of FM, RIF, VNA, LNZ, DAP alone or in combination was determined using anti-biofilm testing and the time-kill assay.
Results:
All isolates were susceptible to LNZ and DPA. The high-level resistance determinant of VAN in these strains was due to VanA-type cassette. MLST revealed two different STs for vancomycin-resistant Enterococcus faecium (VREm) and four different STs for vancomycin-resistant E. faecalis (VREs). Virulence genes in VREs were more than VREm, especially for 4942 isolated from blood. Gene acm and uppS were only identified in VREm, while virulence genes related to cytolysin were only found in E. faecalis. Further in vitro studies indicated FM (83 mg/L) combined with DAP (20.6 mg/L) and DAP monotherapy (47.1 mg/L) had bactericidal effect against VRE isolates at 24h.
Conclusion:
High-level resistance determinant of VAN in tested isolates was due to VanA-type cassette. FM combined with DAP is a potential therapeutic option for VRE infections.
Insights
Fosfomycin combined with daptomycin shows bactericidal effects against vancomycin-resistant Enterococci (VRE). This combination therapy presents a promising option for treating VRE infections, addressing limited clinical choices.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Emergence of vancomycin-resistant Enterococci (VRE) poses a significant threat due to limited therapeutic options.
- VRE infections are associated with high morbidity and mortality, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the vancomycin resistance mechanisms in VRE isolates.
- To evaluate the in vitro efficacy of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), and daptomycin (DAP) alone and in combination against VRE.
Main Methods:
- Eight VRE isolates were analyzed using whole genome sequencing and bioinformatics.
- Antibiotic susceptibility testing, anti-biofilm assays, and time-kill assays were performed.
- Molecular typing (MLST) was conducted to identify different sequence types.
Main Results:
- All VRE isolates were susceptible to linezolid and daptomycin.
- High-level vancomycin resistance was attributed to the VanA-type cassette.
- Fosfomycin combined with daptomycin demonstrated bactericidal activity against VRE at 24 hours.
Conclusions:
- The VanA-type cassette is responsible for high-level vancomycin resistance in the studied VRE isolates.
- Fosfomycin in combination with daptomycin is a potential therapeutic strategy for VRE infections.
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