Cies Jeffrey J, Moore Wayne S, Enache Adela, Chopra Arun
J Pediatr Pharmacol Ther. 2020;25(4):336-339. doi: 10.5863/1551-6776-25.4.336.
Pharmacokinetic data regarding ceftaroline fosamil (CPT) penetration into cerebrospinal fluid (CSF) are limited to a rabbit model (15% inflamed) and adult case reports. We describe serum and CSF CPT concentrations in a 21-year-old, 34.8 kg female, medically complex patient presented with a 4-day history of fevers (Tmax 39.2°C), tachypnea, tachycardia, fatigue, and a 1-week history of pus and blood draining from the ventriculopleural (VPL) shunt. A head CT and an ultrasound of the neck revealed septated complex fluid collection surrounding the shunt. Therapy was initiated with vancomycin and ceftriaxone. Blood and CSF cultures from hospital day (HD) 1 were positive for methicillin-resistant with a CPT MIC of 0.5 mg/L and a vancomycin MIC range of 0.5 to 1 mg/L. On HD 3, CPT was added. On HD 7, simultaneous serum (69.4, 44, and 30.2 mg/L) and CSF (1.7, 2.3, and 2.3 mg/L) concentrations were obtained at 0.25, 1.5, and 4.75 hours from the end of an infusion. Based on these concentrations, CPT CSF penetration ratio ranged from 2.4% to 7.6%. After addition of CPT, the blood and CSF cultures remained negative on a regimen of vancomycin plus CPT. On HD 14, a new left-sided VPL shunt was placed. The patient continued on CPT for a period of 7 days after the new VPL shunt placement. This case demonstrated CPT CSF penetration in a range of 2.4% to 7.6%, approximately half of the rabbit model. This allowed for CSF concentrations at least 50% free time > 4 to 6× MIC of the dosing interval with a dosing regimen of 600 mg IV every 8 hours in a 34.8 kg chronic patient and resulted in a successful clinical outcome with no identified adverse outcomes.
关于头孢洛林酯(CPT)渗入脑脊液(CSF)的药代动力学数据仅限于兔模型(15%炎症模型)和成人病例报告。我们描述了一名21岁、体重34.8千克、患有多种疾病的女性患者血清和脑脊液中的CPT浓度,该患者有4天发热病史(最高体温39.2°C)、呼吸急促、心动过速、疲劳,还有1周从脑室胸膜(VPL)分流管引流脓液和血液的病史。头部CT和颈部超声显示分流管周围有分隔的复杂液体积聚。开始使用万古霉素和头孢曲松进行治疗。住院第1天(HD1)的血液和脑脊液培养显示耐甲氧西林金黄色葡萄球菌阳性,CPT的最低抑菌浓度(MIC)为0.5毫克/升,万古霉素的MIC范围为0.5至1毫克/升。在HD3时加用CPT。在HD7时,在输注结束后的0.25、1.5和4.75小时同时获得血清(69.4、44和30.2毫克/升)和脑脊液(1.7、2.3和2.3毫克/升)浓度。根据这些浓度,CPT脑脊液渗透比范围为2.4%至7.6%。加用CPT后,在万古霉素加CPT治疗方案下,血液和脑脊液培养仍为阴性。在HD14时,放置了新的左侧VPL分流管。在新的VPL分流管放置后,患者继续使用CPT 7天。该病例显示CPT脑脊液渗透率在2.4%至7.6%之间,约为兔模型的一半。这使得在一名34.8千克的慢性患者中,采用每8小时静脉注射600毫克的给药方案时,脑脊液浓度至少有50%的自由时间>给药间隔的4至6倍MIC,并取得了成功的临床结果,未发现不良后果。