caa a22 4500 606156194 CHVBK 20210128100607.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10096-015-2488-5 doi (NATIONALLICENCE)springer-10.1007/s10096-015-2488-5 Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis [Elektronische Daten] [C. Lerche, L. Christophersen, H. Trøstrup, K. Thomsen, P. Jensen, H. Hougen, H. Bundgaard, N. Høiby, C. Moser] The empiric treatment of infective endocarditis (IE) varies widely and, in some places, a regimen of penicillin in combination with an aminoglycoside is administered. The increasing incidence of Staphylococcus aureus IE, poor tissue penetration by aminoglycosides and low frequency of penicillin-susceptible S. aureus may potentially lead to functional tobramycin monotherapy. Therefore, this study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE rat model. Catheter-induced IE at the aortic valves were established with S. aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or tobramycin-treated (n = 13) groups. The treatment group received tobramycin once-daily. Animals were evaluated at 1day post infection (DPI), 2 DPI or 3 DPI. Quantitative bacteriology and cytokine expression were measured for valves, myocardium and serum. A decrease of bacterial load was observed in valves and the spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8) (p ≤ 0.02 and p ≤ 0.01, respectively), but not at 3 DPI (n = 7). Quantitative bacteriology in the myocardium was not different between the groups. Keratinocyte-derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in the tobramycin-treated group (p ≤ 0.03). However, the expression of interleukin (IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was not different between the two groups. In the myocardium, a significant reduction in IL-1b was observed at 2 DPI (p ≤ 0.001) but not at 3 DPI. Tobramycin as functional monotherapy only reduced bacterial load and inflammation transiently, and was insufficient in most cases of S. aureus IE. Springer-Verlag Berlin Heidelberg, 2015 Lerche C. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Christophersen L. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Trøstrup H. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Thomsen K. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Jensen P. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Hougen H. Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark aut Bundgaard H. Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark aut Høiby N. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut Moser C. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/12(2015-12-01), 2349-2357 0934-9723 34:12<2349 2015 34 10096 https://doi.org/10.1007/s10096-015-2488-5 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/s10096-015-2488-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lerche C. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Christophersen L. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Trøstrup H. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Thomsen K. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Jensen P. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Hougen H. Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Bundgaard H. Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Høiby N. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Moser C. Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/12(2015-12-01), 2349-2357 0934-9723 34:12<2349 2015 34 10096