caa a22 4500 606156968 CHVBK 20210128100611.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10096-014-2285-6 doi (NATIONALLICENCE)springer-10.1007/s10096-014-2285-6 Testing the mutant selection window hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin [Elektronische Daten] [Q. Mei, Y. Ye, Y.-L. Zhu, J. Cheng, X. Chang, Y.-Y. Liu, H.-R. Li, J.-B. Li] The purpose of this study was to test the mutant selection window (MSW) hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin. With the in vitro time-kill studies, S. aureus ATCC 29213 [with a minimal concentration that inhibits colony formation by 99% (MIC99) of 2.2μg/mL and a mutant prevention concentration (MPC) of 57.6μg/mL] lost fosfomycin susceptibility at antibiotic concentrations (2×, 4×, and 8× MIC) that are between the lower and upper boundaries of the MSW. In the tissue-cage model, S. aureus was exposed to fosfomycin pharmacokinetics at concentrations below the MIC99, between the MIC99 and the MPC, and above the MPC, respectively. Changes in susceptibility and counts of total and resistant viable bacteria were monitored in tissue-cage fluid obtained daily. However, the selection of resistant mutants was not observed during antibacterial treatment and 48h after the termination of fosfomycin treatment, regardless of the fosfomycin dosage. Besides, we found no differences between the in vitro-isolated mutant and its sensitive parental strain, which indicates the absence of fitness cost of fosfomycin resistance in S. aureus ATCC 29213. These findings demonstrate that agar plate determinations do not fit the MSW for fosfomycin treatment of rabbits infected with S. aureus ATCC 29213; therefore, the existence of the window must be demonstrated not only in vitro but also in vivo. Further research is needed on the exact mechanism of resistance. Springer-Verlag Berlin Heidelberg, 2014 Mei Q. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut Ye Y. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut Zhu Y.-L Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut Cheng J. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut Chang X. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut Liu Y.-Y Anhui Center for Surveillance of Bacterial Resistance, 230022, Hefei, Anhui, China aut Li H.-R Class 7 Grade 2012, the Eight-Year Program on Clinical Medicine, Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, China aut Li J.-B Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/4(2015-04-01), 737-744 0934-9723 34:4<737 2015 34 10096 https://doi.org/10.1007/s10096-014-2285-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-014-2285-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mei Q. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Ye Y. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Zhu Y.-L Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Cheng J. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Chang X. Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Liu Y.-Y Anhui Center for Surveillance of Bacterial Resistance, 230022, Hefei, Anhui, China aut NATIONALLICENCE 700 1- Li H.-R Class 7 Grade 2012, the Eight-Year Program on Clinical Medicine, Xiangya School of Medicine, Central South University, 410013, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Li J.-B Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/4(2015-04-01), 737-744 0934-9723 34:4<737 2015 34 10096