Rapid valve sterilization with meropenem plus ceftolozane/tazobactam combination therapy for Pseudomonas aeruginosa prosthetic valve endocarditis.

IF 3.7 Q2 INFECTIOUS DISEASES
JAC-Antimicrobial Resistance Pub Date : 2025-06-26 eCollection Date: 2025-06-01 DOI:10.1093/jacamr/dlaf112
Valliammai Alaguvel, Anuj K Khetarpal, Allen Jankeel, Wendy A Tapia-Cano, Gabriela Martinez, Arianna Lorenzana, Zoe Hsiao, Warren Rose, George Sakoulas, Erlinda R Ulloa
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引用次数: 0

Abstract

Background: Pseudomonas aeruginosa infective endocarditis (IE) presents a significant clinical challenge, leading to high rates of treatment failure and mortality. Even with the use of antipseudomonal β-lactams combined with aminoglycosides or fluoroquinolones, these therapies often fail to provide clinical resolution and are frequently accompanied by severe adverse effects.

Methods: We report a case of P. aeruginosa prosthetic valve endocarditis successfully treated with a combination of meropenem and ceftolozane/tazobactam. To investigate the synergistic effects of this combination, we conducted checkerboard, time-kill, human whole blood killing, and biofilm assays, as well as a simulated endocardial vegetation (SEV) model.

Results: Meropenem plus ceftolozane/tazobactam combination therapy successfully bridged the patient to cardiac surgery, achieving rapid microbiological clearance and sterile intraoperative valve cultures. While checkerboard assays showed additivity, time-kill assays with subtherapeutic antibiotic concentrations did not demonstrate synergy in standard media. However, significant synergy was observed in human whole blood and biofilm environments, with modestly improved activity in the SEV model.

Conclusions: The combination of meropenem and ceftolozane/tazobactam demonstrates promising synergy in physiologically relevant conditions, offering a potentially safer alternative for treating P. aeruginosa IE and stabilizing complex patients prior to cardiac surgery. Further clinical investigation is needed to evaluate its efficacy and safety profile in severe Pseudomonas infections, including IE.

美罗培南联合头孢唑烷/他唑巴坦联合快速瓣膜消毒治疗铜绿假单胞菌人工瓣膜心内膜炎。
背景:铜绿假单胞菌感染性心内膜炎(IE)是一个重大的临床挑战,导致治疗失败率和死亡率高。即使使用抗假单胞菌β-内酰胺类药物与氨基糖苷类或氟喹诺酮类药物联合使用,这些治疗方法往往不能提供临床解决方案,并经常伴有严重的不良反应。方法:我们报告一例铜绿假单胞菌人工瓣膜心内膜炎,美罗培南联合头孢托唑烷/他唑巴坦治疗成功。为了研究这种组合的协同效应,我们进行了棋盘、时间杀伤、人全血杀伤和生物膜试验,以及模拟心内膜植被(SEV)模型。结果:美罗培南加头孢唑烷/他唑巴坦联合治疗成功地将患者转移到心脏手术,实现了快速的微生物清除和术中无菌瓣膜培养。棋盘试验显示可加性,而亚治疗抗生素浓度的时间杀伤试验在标准培养基中没有显示协同作用。然而,在人全血和生物膜环境中观察到显著的协同作用,在SEV模型中活性略有提高。结论:美罗培南联合头孢唑烷/他唑巴坦在生理相关条件下显示出良好的协同作用,为治疗铜绿假单胞菌IE和心脏手术前稳定复杂患者提供了一种潜在的更安全的选择。需要进一步的临床研究来评估其在严重假单胞菌感染(包括IE)中的有效性和安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
5.30
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