Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis

• Published in: European journal of clinical microbiology & infectious diseases 2015-12, Vol.34 (12), p.2349-2357
• Main Authors: Lerche, C. J., Christophersen, L. J., Trøstrup, H., Thomsen, K., Jensen, P. Ø., Hougen, H. P., Bundgaard, H., Høiby, N., Moser, C.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Aortic Valve - microbiology; Aortic Valve - pathology; Bacterial Load; Bacteriology; Biomedical and Life Sciences; Biomedicine; Cardiology; Catheters; Chemokines; Cytokines; Cytokines - analysis; Disease Models, Animal; Endocarditis; Endocarditis, Bacterial - drug therapy; Endocarditis, Bacterial - pathology; Granulocytes; Internal Medicine; Medical instruments; Medical Microbiology; Myocardium - pathology; Original Article; Pathogenesis; Penicillin; Rats, Wistar; Spleen - microbiology; Staphylococcal Infections - drug therapy; Staphylococcal Infections - pathology; Staphylococcus aureus - drug effects; Staphylococcus infections; Tobramycin - administration & dosage; Treatment Outcome
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-015-2488-5

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.