Barnea Y, Navon-Venezia S, Kuzmenko B, Artzi N, Carmeli Y
Division of Epidemiology & Laboratory for Molecular Epidemiology and Antimicrobials Research, Tel-Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Eur J Clin Microbiol Infect Dis. 2014 Mar;33(3):325-9. doi: 10.1007/s10096-013-1959-9. Epub 2013 Sep 14.
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.
正中开胸术后耐甲氧西林金黄色葡萄球菌（MRSA）纵隔炎是心脏手术的一种主要并发症，其发病率和死亡率都很高。我们在一种新的纵隔炎大鼠模型中评估了头孢比普甲磺酸盐的疗效，并将其与万古霉素进行比较。该模型应用于92只大鼠。在正中开胸术后立即通过向胸骨注射MRSA（菌株3020，1×10(7) cfu/大鼠）诱导感染。24小时后，将大鼠（每组6 - 8只）通过以下方式进行腹腔内治疗5天或14天：（i）生理盐水（对照组，每8小时一次），（ii）头孢比普甲磺酸盐（70或100 mg/kg，每8小时一次），或（iii）万古霉素（50 mg/kg，每12小时一次）。通过胸骨和脾脏组织中细菌cfu的减少来确定疗效。使用曼 - 惠特尼检验进行比较。与对照组相比，以及与5天万古霉素治疗（导致非显著减少，p = 0.07）相比，两种测试剂量的头孢比普甲磺酸盐进行5天疗程治疗均导致胸骨中MRSA载量显著减少（p < 0.01）。与万古霉素相似，头孢比普甲磺酸盐进行更长疗程（14天）治疗导致胸骨中MRSA完全清除。与生理盐水处理的大鼠相比，头孢比普甲磺酸盐在消除MRSA向脾脏扩散方面也显示出显著效果。头孢比普甲磺酸盐在大鼠模型中治疗MRSA纵隔炎有效。在5天疗程中，头孢比普甲磺酸盐显示胸骨中MRSA计数显著减少，且优于万古霉素。14天后，头孢比普甲磺酸盐和万古霉素在超过50%的大鼠中均显示胸骨中MRSA清除，其余大鼠几乎完全清除。
