Infectious Diseases Service, Hospital del Mar, Barcelona, Spain.
Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
Microbiol Spectr. 2022 Jun 29;10(3):e0089222. doi: 10.1128/spectrum.00892-22. Epub 2022 Jun 13.
The aim of this study was to compare the efficacy of intermittent (1-h), extended (4-h), and continuous ceftolozane-tazobactam (C/T) infusion against three extensively drug-resistant (XDR) sequence type (ST) 175 P. aeruginosa isolates with different susceptibilities to C/T (MIC = 2 to 16 mg/L) in a 7-day hollow-fiber infection model (HFIM). C/T in continuous infusion achieved the largest reduction in total number of bacterial colonies in the overall treatment arms for both C/T-susceptible and -resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. These data suggest that continuous C/T infusion should be considered a potential treatment for infections caused by XDR P. aeruginosa isolates, including nonsusceptible ones. Proper use of C/T dosing regimens may lead to better clinical management of XDR P. aeruginosa infections. Ceftolozane-tazobactam (C/T) is an antipseudomonal antibiotic with a high clinical impact in treating infection caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates, but resistance is emerging. Given its time-dependent behavior, C/T continuous infusion can improve exposure and therefore the pharmacokinetic/pharmacodynamic target attainment. We compared the efficacy of intermittent, extended, and continuous C/T infusion against three XDR ST175 P. aeruginosa isolates with different C/T MICs by means of an dynamic hollow-fiber model. We demonstrated that C/T in continuous infusion achieved the largest reduction in bacterial density in the overall treatment arms for both susceptible and resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. Through this study, we want to demonstrate that developing individually tailored antimicrobial treatments is becoming essential. Our results support the role of C/T level monitoring and of dose adjustments for better clinical management and outcomes.
本研究旨在通过 7 天中空纤维感染模型（HFIM）比较间歇性（1 小时）、延长性（4 小时）和连续性头孢他啶-他唑巴坦（C/T）输注对三种不同药敏性（MIC = 2 至 16 mg/L）广泛耐药（XDR）ST175 铜绿假单胞菌分离株的疗效。对于 C/T 敏感和耐药分离株，连续 C/T 输注在所有治疗组中均能最大程度地减少总细菌菌落数，且是唯一对所有三种分离株均具有杀菌活性的方案。这些数据表明，连续 C/T 输注应被视为治疗 XDR 铜绿假单胞菌感染的一种潜在治疗方法，包括对 C/T 不敏感的感染。适当使用 C/T 给药方案可能会改善 XDR 铜绿假单胞菌感染的临床管理。头孢他啶-他唑巴坦（C/T）是一种抗假单胞菌抗生素，在治疗广泛耐药（XDR）铜绿假单胞菌感染方面具有重要的临床意义，但耐药性正在出现。鉴于其时间依赖性特性，C/T 连续输注可改善暴露度，从而提高药代动力学/药效学目标的实现。我们通过动态中空纤维模型比较了间歇性、延长性和连续性 C/T 输注对三种不同 C/T MIC 的 XDR ST175 铜绿假单胞菌分离株的疗效。我们证明，对于敏感和耐药分离株，连续 C/T 输注在所有治疗组中均能最大程度地降低细菌密度。它也是唯一对所有三种分离株均具有杀菌活性的方案。通过这项研究，我们希望证明开发个体化的抗菌治疗方案变得至关重要。我们的结果支持 C/T 水平监测和剂量调整在改善临床管理和结果方面的作用。
