title: In vitro and intracellular activities of fosfomycin against clinical strains of Listeria monocytogenes.
abstract: This study was designed to evaluate the potential role of fosfomycin as a therapeutic agent in human listeriosis. The in vitro activity of fosfomycin against 154 Listeria monocytogenes clinical isolates under conditions that mimic the induction of prfA expression was determined and was correlated with fosfomycin intracellular antimicrobial activity. In vitro, partial induction of prfA expression is achieved through bacterial growth in brain-heart infusion agar supplemented with activated charcoal (BHIC). A fosfomycin pharmacokinetic/pharmacodynamic breakpoint of ≤64 mg/L was estimated using a Monte Carlo simulation to assess the success of an intravenous fosfomycin dose of 300 mg/kg/day over 5000 individuals. Eighty strains (51.9%) were susceptible to fosfomycin in BHIC, with minimum inhibitory concentrations (MICs) of ≤64 mg/L; 13 strains (8.4%) had the epidemic clone (EC) marker. In addition, 27 strains (17.5%) had a three doubling dilutions reduction in the MIC from ≥1024 mg/L to 128 mg/L (96-128 mg/L by Etest). The fosfomycin modal MIC is lower under prfA expression. However, this effect is smaller in terms of clinical categorisation of isolates and can be influenced by the serotype and clonal type. In A549 cells, the reductions in bacterial inocula of the two susceptible isolates studied after 1h and 24h of incubation with fosfomycin at 0.5× the human maximum serum concentration (Cmax) were 45.8% and 46.6%, and 93.8% and 99.1%, respectively. Slightly higher reductions were found with fosfomycin at 1× Cmax. The resistant strain tested showed significantly lower reductions in all assays.
authors: Infectious Diseases, Clinical Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain; Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. Electronic address: jalepe@cica.es.
authors: José A
authors: JA
authors: Lepe
authors: Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain; Microbiology Department, University of Seville, Seville, Spain.
authors: María J
authors: MJ
authors: Torres
authors: Infectious Diseases, Clinical Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain; Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors: Younes
authors: Y
authors: Smani
authors: Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors: Raquel
authors: R
authors: Parra-Millán
authors: Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors: Jerónimo
authors: J
authors: Pachón
authors: Infectious Diseases, Clinical Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors: Isabel
authors: I
authors: Vazquez-Barba
authors: Infectious Diseases, Clinical Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain; Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain; Microbiology Department, University of Seville, Seville, Spain.
authors: Javier
authors: J
authors: Aznar
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D004847:Epithelial Cells / Q000382:microbiology; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010454:Peptide Termination Factors / Q000096:biosynthesis; D015533:Transcriptional Activation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D005578:Fosfomycin
keywords: Charcoal; Fosfomycin; Listeria; prfA