In vitro and intracellular activities of fosfomycin against clinical strains of Listeria monocytogenes |
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Institution: | 1. Infectious Diseases, Clinical Microbiology and Preventive Medicine Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain;2. Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain;3. Microbiology Department, University of Seville, Seville, Spain;1. Instituto de Agrobiotecnología del Litoral (UNL–CONICET), Facultad de Bioquímica y Ciencias Biológicas, Paraje “El Pozo” CC 242, S3000ZAA Santa Fe, Argentina;2. Estación Experimental Agropecuaria Rafaela, Instituto Nacional de Tecnología Agropecuaria, Rafaela, Santa Fe, Argentina;1. Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Department of Infectious Disease, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore;2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore;1. INSERM U914 ‘Emerging Resistance to Antibiotics’, K.-Bicêtre, France;2. Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland;3. International Center for Medical Research and Training, CIDEIM, Cali, Colombia;1. 1st Division of Infectious Diseases, ‘Luigi Sacco’ Hospital, via GB Grassi 74, Milan 20157, Italy;2. Division of Infectious Diseases, ‘Careggi’ Hospital, Florence, Italy;3. Infectious Diseases Clinic, ‘San Martino’ Hospital, Genoa, Italy;4. Infectious Diseases Clinic, ‘Santa Maria Annunziata’ Hospital, Florence, Italy;5. 3rd Division of Infectious Diseases, Istituto Nazionale di Malattie Infettive ‘Lazzaro Spallanzani’, Rome, Italy;6. Division of Infectious Diseases, ‘Ospedale di Circolo’, Busto Arsizio, Italy;7. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Perugia, Italy;8. Infectious Diseases Clinic, ‘Luigi Sacco’ Hospital, Milan, Italy;9. Infectious Diseases Clinic, ‘San Gerardo de’ Tintori’ Hospital, Monza, Italy;10. Infectious Diseases Clinic, Azienda Ospedaliera Universitaria Policlinico, Modena, Italy;11. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy;12. Division of Infectious Diseases, ‘Policlinico G. Martino’, Messina, Italy;13. Division of Infectious Diseases, ‘Santo Spirito’ Hospital, Pescara, Italy;14. Division of Infectious Diseases, ‘Santa Maria della Misericordia’ Hospital, Grosseto, Italy;15. Infectious Diseases Unit, University of Catania, ARNAS Garibaldi, Catania, Italy;p. 2nd Division of Internal Medicine, Azienda Ospedaliera di Desio e Vimercate Hospital, Vimercate, Italy;1. Infection and Immunity Research Group, Glasgow Dental School and Hospital, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK;2. Institute of Healthcare Associated Infections, School of Health, Nursing and Midwifery, University of the West of Scotland, Glasgow, UK |
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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 1 h and 24 h 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. |
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Keywords: | Listeria Fosfomycin Charcoal |
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