Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmacy, Baptist Memorial Hospital-Memphis, Memphis, TN, USA.
Clin Ther. 2019 Nov;41(11):2397-2415.e8. doi: 10.1016/j.clinthera.2019.09.010. Epub 2019 Nov 1.
Pseudomonas aeruginosa is a commonly isolated nosocomial pathogen for which treatment options are often limited for multidrug-resistant isolates. In addition to newer available antimicrobial agents active against P. aeruginosa, strategies such as extended (eg, prolonged or continuous) infusion have been suggested to optimize the pharmacokinetic and pharmacodynamic profiles of β-lactams. Literature regarding clinical outcomes for extended infusion β-lactams has been controversial; however, this use seems most beneficial in patients with severe illness. Prolonged infusion of β-lactams (eg, 3- to 4-hour infusion) can enhance the pharmacodynamic target attainment via increasing the amount of time throughout the dosing interval to which the free drug concentration remains above the MIC (minimum inhibitory concentration) of the organism (fT > MIC). This systematic review summarizes current literature related to the probability of target attainment (PTA) of various antipseudomonal β-lactam regimens administered as prolonged infusions in an effort to provide guidance in selecting optimal dosing regimens and infusion times for the treatment of P. aeruginosa infections.
A literature search for all pertinent studies was performed by using the PubMed database (with no year limit) through March 31, 2019.
Thirty-nine studies were included. Although many standard antipseudomonal β-lactam intermittent infusion regimens can provide adequate PTA against most susceptible isolates, prolonged infusion may enhance percent fT > MIC for organisms with higher MICs (eg, nonsusceptible) or patients with altered pharmacokinetic profiles (eg, obese, critically ill, those with febrile neutropenia).
Prolonged infusion β-lactam regimens can enhance PTA against nonsusceptible P. aeruginosa isolates and may provide a potential therapeutic option for multidrug-resistant infections. Before implementing prolonged infusion antipseudomonal β-lactams, institutions should consider the half-life of the antibiotic, local incidence of P. aeruginosa infections, antibiotic MIC distributions or MICs isolated from individual patients, individual patient characteristics that may alter pharmacokinetic variables, and PTA (eg, critically ill), as well as implementation challenges.
铜绿假单胞菌是一种常见的医院获得性病原体，其治疗选择往往因多药耐药分离株而受到限制。除了新型的抗铜绿假单胞菌的抗菌药物外，还建议采用延长（如延长或持续）输注等策略来优化β-内酰胺类药物的药代动力学和药效学特征。关于延长输注β-内酰胺类药物的临床结局的文献一直存在争议；然而，这种用法在重病患者中似乎最有益。延长输注β-内酰胺类药物（例如，3 至 4 小时输注）可以通过增加整个给药间隔内药物浓度保持在最低抑菌浓度（MIC）以上的时间（游离药物浓度高于生物体的 MIC（fT> MIC））来增强药效学目标的实现。本系统评价总结了目前关于延长输注各种抗假单胞菌β-内酰胺类药物方案的目标实现概率（PTA）的文献，旨在为选择治疗铜绿假单胞菌感染的最佳给药方案和输注时间提供指导。
通过使用 PubMed 数据库（无年限限制）对所有相关研究进行文献检索，检索截止日期为 2019 年 3 月 31 日。
共纳入 39 项研究。虽然许多标准的抗假单胞菌β-内酰胺类药物间歇性输注方案可以对大多数敏感分离株提供足够的 PTA，但延长输注可能会提高 MIC 较高的生物体（例如，不敏感）或药代动力学特征改变的患者（例如，肥胖、重病、发热性中性粒细胞减少症患者）的 fT> MIC 的百分比。
延长输注β-内酰胺类药物方案可以提高对不敏感的铜绿假单胞菌分离株的 PTA，并且可能为多药耐药感染提供潜在的治疗选择。在实施延长输注抗假单胞菌β-内酰胺类药物之前，机构应考虑抗生素的半衰期、铜绿假单胞菌感染的局部发生率、抗生素 MIC 分布或个体患者分离的 MIC、可能改变药代动力学变量的个体患者特征、PTA（例如，重病）以及实施挑战。
