Stein Gary E, Yasin Fadi, Smith Curtis, Scharmen Amy, Havlichek Daniel, Bill Charles
1 Department of Medicine, Michigan State University , East Lansing, Michigan.
Surg Infect (Larchmt). 2015 Apr;16(2):169-73. doi: 10.1089/sur.2014.098. Epub 2015 Mar 31.
Ceftaroline is a broad-spectrum cephalosporin antibiotic with activity against drug-resistant bacteria, including strains of methicillin-resistant Staphylococcus aureus (MRSA), and may be useful to prevent and treat ventriculostomy-related infections (VRIs). The purpose of this study was to analyze the pharmacokinetics and pharmacodynamics of prophylactic ceftaroline in neurosurgical patients with an external ventricular drain (EVD).
Adult patients in the neurosurgical intensive care unit with an EVD were given prolonged prophylaxis with ceftaroline. Serum and cerebral spinal fluid (CSF) were obtained simultaneously at 2, 6, and 12 h after initiation of the fourth dose of ceftaroline and concentrations were measured by a liquid chromatography tandem mass spectrometry assay. Time-kill curves against isolates of coagulase-negative S. aureus, methicillin-sensitive S. aureus, MRSA, and Streptococcus pneumoniae were determined in serum and CSF at each collection time point.
A total of five patients with a mean age of 63 y and mean weight of 83 kg were enrolled. The mean CSF:serum penetration ratios of ceftaroline were 0.005 (0.5%), 0.021 (2.1%), and 0.043 (4.3%) at 2, 6, and 12 h, respectively. The mean ceftaroline exposure ratio area under the curve (AUC)csf/AUCserum) was 0.011 (1.1%). Bactericidal activity at each collection time point was observed against each strain of staphylococci from serum samples and a penicillin-sensitive strain of S. pneumoniae from CSF samples.
This investigation suggests that ceftaroline could have clinical utility for the prevention of VRIs in patients with EVDs.
头孢洛林是一种广谱头孢菌素抗生素，对耐药菌具有活性，包括耐甲氧西林金黄色葡萄球菌（MRSA）菌株，可能有助于预防和治疗脑室造口相关感染（VRI）。本研究的目的是分析预防性使用头孢洛林在接受外置脑室引流（EVD）的神经外科患者中的药代动力学和药效学。
神经外科重症监护病房中带有EVD的成年患者接受了头孢洛林的长期预防治疗。在给予第四剂头孢洛林后2、6和12小时同时采集血清和脑脊液（CSF），并通过液相色谱串联质谱分析法测量浓度。在每个采集时间点测定血清和CSF中针对凝固酶阴性金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、MRSA和肺炎链球菌分离株的时间-杀菌曲线。
共纳入5例患者，平均年龄63岁，平均体重83 kg。头孢洛林的平均脑脊液：血清渗透比在2、6和12小时分别为0.005（0.5%）、0.021（2.1%）和0.043（4.3%）。头孢洛林的平均暴露比曲线下面积（AUC）脑脊液/AUC血清为0.011（1.1%）。在每个采集时间点，观察到血清样本中针对每种葡萄球菌菌株以及CSF样本中针对青霉素敏感的肺炎链球菌菌株的杀菌活性。
本研究表明，头孢洛林可能对预防EVD患者的VRI具有临床应用价值。
