Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL Center, Tampa, FL, USA.
Ann Pharmacother. 2010 Mar;44(3):582-6. doi: 10.1345/aph.1M480. Epub 2010 Feb 23.
To describe cerebral spinal fluid (CSF) penetration of tigecycline.
A 38-year-old woman experienced a right internal carotid artery dissection and right anterior and middle cerebral artery strokes due to unknown causes and subsequently developed vasogenic edema requiring right hemi-craniectomy. Her postoperative course was complicated by multiple infections, and she developed multidrug, carbapenem-resistant Acinetobacter baumannii cerebritis. She was treated with a prolonged course of multiple antibiotics, including 18 days of therapy with tigecycline. Time-paired serum and CSF samples were obtained, and tigecycline concentrations were analyzed by high-performance liquid chromatography. We report serial, steady-state, serum, and CSF concentrations of tigecycline when administered in the Food and Drug Administration-approved dose of 50 mg every 12 hours. CSF concentrations remained relatively stable, suggesting that tigecycline did not accumulate in the CSF, at least in our patient. Tigecycline concentrations in the CSF were between 0.035 and 0.048 mg/L, while corresponding serum concentrations were 0.097-0.566 mg/L. The calculated tigecycline penetration ratio in this patient ranged from 0% to 52%, depending on the calculation methodology utilized.
Concentrations, regardless of sample timing relative to dose, remained relatively stable in the CSF of our patient. The pharmacodynamic profile of tigecycline is not completely elucidated; however, it is presumed that the drug must be at the site of infection for efficacy. Our patient never obtained tigecycline concentrations in excess of the minimum inhibitory concentration for A. baumannii in either the serum or the CSF.
Our patient experienced low CSF tigecycline concentrations and failed to achieve a clinical response while on therapy. CSF drug disposition of tigecycline requires further systematic study to fully elucidate the pharmacokinetic profile. Reduced CSF concentrations urge caution in the treatment of cerebritis with standard dosing of tigecycline.
描述替加环素在脑脊液中的渗透情况。
一名 38 岁女性因不明原因发生右侧颈内动脉夹层和右侧前、中脑动脉卒中,继而出现血管源性水肿,需要行右侧半颅骨切除术。她的术后病程复杂,合并多种感染,并发生了多药、耐碳青霉烯鲍曼不动杆菌性脑脊髓炎。她接受了多种抗生素的长期治疗,包括 18 天的替加环素治疗。我们报告了在食品和药物管理局批准的剂量(每 12 小时 50 毫克)下给药时,替加环素在血清和脑脊液中的时间配对样本和浓度。我们报告了替加环素在血清和脑脊液中的浓度,结果显示,替加环素在该患者中并未积累,至少在我们的患者中是这样。替加环素在脑脊液中的浓度在 0.035 至 0.048 毫克/升之间,而相应的血清浓度在 0.097 至 0.566 毫克/升之间。根据所使用的计算方法,该患者的替加环素穿透率范围在 0%至 52%之间。
无论样本与剂量的时间关系如何,替加环素在我们患者的脑脊液中的浓度仍然相对稳定。替加环素的药效学特征尚未完全阐明;然而,据推测,该药物必须在感染部位才能发挥疗效。我们的患者在血清或脑脊液中从未获得超过鲍曼不动杆菌最小抑菌浓度的替加环素浓度。
我们的患者经历了替加环素在脑脊液中的低浓度和治疗期间的临床反应失败。替加环素在脑脊液中的药物分布需要进一步系统研究,以充分阐明其药代动力学特征。降低的脑脊液浓度在使用替加环素标准剂量治疗脑脊髓炎时应谨慎。