title: Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis.
abstract: 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 1 day 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.
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark. cjl@dadlnet.dk.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lerche
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.
authors.forename: L J
authors.initials: LJ
authors.lastname: Christophersen
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Trøstrup
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Thomsen
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.
authors.forename: P Ø
authors.initials: PØ
authors.lastname: Jensen
authors.affiliation: Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H P
authors.initials: HP
authors.lastname: Hougen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Bundgaard
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.|Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Department of Clinical Microbiology 9301, Copenhagen University Hospital, Rigshospitalet, Juliane Maries vej 22, 2100, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Moser
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001021:Aortic Valve / Q000382:microbiology / Q000473:pathology; D058491:Bacterial Load; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects*; D014031:Tobramycin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D014031:Tobramycin