Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | European Journal of Clinical Microbiology & Infectious Diseases |
Vol/bind | 34 |
Udgave nummer | 12 |
Sider (fra-til) | 2349-2357 |
Antal sider | 9 |
ISSN | 0934-9723 |
DOI | |
Status | Udgivet - 1 dec. 2015 |
ID: 160026103