Introduction. Ceftobiprole is an advanced-generation broad-spectrum parenteral cephalosporin with activity against MSSA and MRSA. Gap Statement. Ceftobiprole is not currently approved for use to treat S. aureus bacteremia and phase three clinical trials are taking place. Drug approval requires further pre-clinical evidence to support this new indication. Aim. The aim of this study was to evaluate the efficacy of ceftobiprole at the human equivalent efficacious exposure (considering a 500 mg q8h dosing regimen infused over 2 h) against MSSA and MRSA strains in a neutropenic murine model of bacteremia and disseminated infection. Methodology. Two bioluminescent-tagged strains (one MSSA and one MRSA strain) were selected based on their in vitro susceptibility and in vivo growth profiles. Bacterial c.f.u. counts in the blood, lung, kidney, and liver were determined 48 h post-infection or after death. The bioluminescent-tag allowed the visualization of the real-time effects of ceftobiprole therapy compared to the natural progression of the infection in untreated controls. Results. Treatment with ceftobiprole resulted in a significant reduction of the bacterial load with the bioluminescence reduced by 2-log units and bacterial c.f.u. counts reduced by 3- to 6-log units, depending on the organ and bacterial strain. Survival was 100 % in the ceftobiprole-treated group compared to only 0–20 % survival in the untreated control animals for both strains tested. Conclusion. These results suggest that treatment with ceftobiprole using a 500 mg q8h dosing regimen studied in several successful phase three trials, has potential as an antibiotic therapy to treat bacteremia and associated disseminated infections caused by either methicillin-susceptible or methicillin-resistant strains of S. aureus .

中文翻译：

---

头孢比普罗在菌血症和播散性感染小鼠模型中的功效

介绍。Ceftobiprole 是一种新一代广谱肠外头孢菌素，具有抗 MSSA 和 MRSA 活性。差距声明。头孢比普罗目前尚未被批准用于治疗金黄色葡萄球菌菌血症，并且正在进行三期临床试验。药物批准需要进一步的临床前证据来支持这一新适应症。目的。本研究的目的是在中性粒细胞减少性鼠菌血症和播散性感染模型中评估头孢比普罗在人体等效有效暴露量（考虑在 2 小时内输注 500 mg q8h 给药方案）对 MSSA 和 MRSA 菌株的功效。方法。根据体外敏感性和体内生长情况选择两种生物发光标记菌株（一种 MSSA 和一种 MRSA 菌株）。感染后 48 小时或死亡后测定血液、肺、肾和肝脏中的细菌 CFU 计数。与未经治疗的对照中感染的自然进展相比，生物发光标签可以使头孢比普罗治疗的实时效果可视化。结果。头孢比普罗治疗导致细菌负荷显着减少，生物发光减少 2 个对数单位，细菌 cfu 计数减少 3 至 6 个对数单位，具体取决于器官和菌株。对于测试的两种菌株，头孢比普罗治疗组的存活率为 100%，而未经治疗的对照动物的存活率仅为 0-20%。结论。这些结果表明，在几项成功的三期试验中研究的使用 500 mg q8h 给药方案的头孢比普罗治疗有潜力作为抗生素疗法来治疗由甲氧西林敏感或甲氧西林耐药金黄色葡萄球菌菌株引起的菌血症和相关播散性感染。