Department of Pharmacy, Edward Hines, Jr. VA Medical Center, Hines, IL, 60141, USA.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, 06102, USA.
Infect Dis Ther. 2016 Mar;5(1):73-9. doi: 10.1007/s40121-016-0104-3. Epub 2016 Mar 2.
Ceftolozane/tazobactam (C/T) is a novel antibiotic approved for complicated intra-abdominal and urinary tract infections caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for treatment of bacteremia and even less so about the appropriateness of the renally defined regimens. We describe a case of a 66-year-old man with a history of chronic kidney disease (baseline Cr = 3-4 mg/dl) and recurrent nephrolithiasis with bilateral stents who had positive concurrent urine and blood cultures for MDR Pseudomonas aeruginosa (PSA), susceptible only to amikacin and colistin. Due to the MDR phenotype and his underlying kidney disease, the 375 mg (250 mg/125 mg) dose of C/T was given as monotherapy every 8 h for his bloodstream infection.
Once steady state was anticipated, blood was obtained at the end of infusion (1 h), and at 3, 5 and 8 h for drug concentration determination using a validated high-performance liquid chromatography method at the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford.
The minimum inhibitory concentration (MIC) for the PSA was 2/4 for C/T, indicating susceptibility. Concentration of ceftolozane of 21.87 µg/ml at 8 h indicated that serum concentrations were maintained above the MIC throughout the dosing interval. The patient was given 25 days of C/T and experienced a successful clinical outcome. Blood cultures obtained at 1 and 3 weeks after completion of treatment remained sterile. No adverse events were attributed to C/T.
In this patient, the renally adjusted dose of C/T was safe and provided sufficiently high drug concentrations that exceeded the MIC of the infecting organism over the course of therapy. More data are required to determine the clinical utility of C/T in the setting of MDR PSA bacteremia.
头孢他唑巴坦（C/T）是一种新型抗生素，获批用于治疗由革兰氏阳性和革兰氏阴性菌引起的复杂性腹腔内和尿路感染，包括一些 MDR 株。对于该药物治疗菌血症的应用知之甚少，对于根据肾功能定义的方案的适宜性则了解得更少。我们描述了一例 66 岁男性的病例，该患者患有慢性肾脏病（基线 Cr 为 3-4mg/dl）和复发性肾结石，双侧支架置入，同时存在对氨基糖苷类和多粘菌素敏感的耐多药铜绿假单胞菌（PSA）的尿液和血液阳性培养。由于该患者存在 MDR 表型和基础肾脏疾病，给予其每 8 小时静脉滴注一次 375mg（250mg/125mg）剂量的 C/T 单药治疗菌血症。
一旦达到稳态，在哈特福德医院感染性疾病研究与开发中心采用经验证的高效液相色谱法，于输注结束时（1 小时）以及 3、5 和 8 小时取血样，以测定血药浓度。
PSA 的最低抑菌浓度（MIC）对于 C/T 为 2/4，表明敏感性。8 小时时头孢他唑巴坦的浓度为 21.87µg/ml，表明血清浓度在整个给药间隔内保持在 MIC 以上。患者接受了 25 天的 C/T 治疗，并获得了成功的临床转归。治疗结束后 1 周和 3 周时获得的血培养均无菌。未将任何不良事件归因于 C/T。
在该患者中，根据肾功能调整剂量的 C/T 是安全的，并且提供了足够高的药物浓度，在整个治疗过程中超过了感染病原体的 MIC。需要更多的数据来确定 C/T 在 MDR PSA 菌血症中的临床应用价值。
