Methicillin-resistant Staphylococcus aureus (MRSA)
mediastinitis after
median sternotomy is a major complication of cardiac surgery with significant morbidity and mortality rates. We evaluated the efficacy of
ceftobiprole medocaril in a new rat model of
mediastinitis and compared it to
vancomycin. The model was induced in 92 rats.
Infection was induced immediately after
median sternotomy by the injection of MRSA (strain 3020, 1 × 10(7) cfu/rat) into the sternal bone. After 24 h, rats (groups of 6-8) were treated intraperitoneally for 5 days or 14 days by either: (i) saline (control, q8h), (ii)
ceftobiprole medocaril (70 or 100 mg/kg, q8h), or (iii)
vancomycin (50 mg/kg, q12h). Efficacy was determined by a reduction in bacterial cfu in the sternum and spleen tissues. Comparisons were performed using the Mann-Whitney test. A 5-day treatment course of
ceftobiprole at both doses tested lead to a significant reduction in MRSA load in the sternum (p < 0.01) as compared to the control group and compared to 5-day
vancomycin treatment, which lead to a non-significant reduction (p = 0.07). Longer treatment (14 days) with
ceftobiprole lead to a complete clearance of MRSA from the sternum, similarly to
vancomycin.
Ceftobiprole also showed a significant effect on eliminating MRSA dissemination to the spleen compared to saline-treated rats.
Ceftobiprole was effective in treating MRSA
mediastinitis in the rat model. In the 5-day course,
ceftobiprole showed a significant reduction in sternal MRSA counts and was superior to
vancomycin. After 14 days, both
ceftobiprole and
vancomycin showed clearance of MRSA from the sternum in more than 50 % of rats and almost complete clearance in the remainder.