Pharmacy Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
Eur J Drug Metab Pharmacokinet. 2022 Jul;47(4):561-566. doi: 10.1007/s13318-022-00772-x. Epub 2022 Jun 3.
Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this study was to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosa infections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure.
Patients with MDR/XDR P. aeruginosa infections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT ≥ MIC) of the causative pathogen. Dose changes were performed according to TDM results.
Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosa infection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9 g/day (ceftolozane 2 g + tazobactam 1 g, every 8 h; p = 0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%).
The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosa infections.
延长输注头孢他啶/他唑巴坦（C/T）是一种用于增加多药耐药或广泛耐药 MDR/XDR 革兰氏阴性微生物治疗的药代动力学/药效学目标的策略。本研究的目的是描述我们对多药耐药/广泛耐药铜绿假单胞菌感染患者进行 C/T 延长输注或间歇性输注的治疗药物监测（TDM）经验。我们感兴趣的结果是药代动力学/药效学目标的实现和临床治愈。
2018 年 2 月至 2020 年 2 月期间，我们招募了接受 C/T 治疗的 MDR/XDR 铜绿假单胞菌感染患者。作为 TDM 计划的一部分，采集了血样。C/T 的药代动力学/药效学治疗目标被定义为在给药间隔的 100%时间内游离浓度高于致病病原体的最低抑菌浓度（MIC）（100%ƒT≥MIC）。根据 TDM 结果进行剂量调整。
共纳入 40 例患者：13 例（32.5%）为确证性 MDR，27 例（67.5%）为 XDR 铜绿假单胞菌感染。32 例（80%）患者接受 C/T 延长输注，8 例（20%）患者接受 C/T 间歇性输注。与间歇性输注组相比，延长输注组的剂量较低[3（9.4%）例 vs. 5（62.5%）例]接受 9 g/天的剂量（头孢他啶 2 g + 他唑巴坦 1 g，每 8 小时一次；p=0.004）。两组患者均达到药代动力学/药效学目标，C/T 浓度在>50%的患者中均超过 10×MIC。19 例（47.5%）患者根据 TDM 建议减少剂量，其中 16 例（84.2%）在延长输注组。高比例的患者达到临床治愈（82.5%）。
通过 TDM 指导剂量的延长输注给予 C/T，即使在较低剂量下也能达到药代动力学/药效学目标。C/T 对治疗多药耐药/广泛耐药铜绿假单胞菌感染具有高疗效。
