Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Spain.
Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Spain.
J Glob Antimicrob Resist. 2019 Sep;18:37-44. doi: 10.1016/j.jgar.2019.04.012. Epub 2019 May 30.
Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option.
This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015).
Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates.
In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection.
These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial.
广泛耐药（XDR）铜绿假单胞菌（P. aeruginosa），尤其是高风险克隆的铜绿假单胞菌，日益受到关注，因为治疗选择有限。多年来，黏菌素单药治疗一直是唯一可用的治疗方法，但众所周知，这并不是一种最佳的治疗方法。黏菌素与另一种抗生素的联合治疗可能是一种可行的治疗选择。
本研究旨在调查针对 2015 年在西班牙多中心研究中获得的 20 株 XDR 铜绿假单胞菌分离株的有效抗生素组合。
使用 45 个棋盘法，其中包含六种抗假单胞菌抗生素（阿米卡星、氨曲南、头孢他啶、美罗培南、黏菌素和头孢他啶/他唑巴坦），通过计算抑菌浓度指数（FICI），以确定组合是否具有协同或相加作用。通过 24 小时的时间杀伤分析，平均评估了 15 种不同的方案，以评估三种最常见的高风险克隆（ST175、ST235、ST111）。在三种高风险克隆中显示协同作用的组合在所有研究的 XDR 分离株中均得到验证。
在时间杀伤曲线中，未经处理的对照组失败，单独使用每种研究方案也失败。在最初研究的三种高风险克隆中，两种组合具有协同作用：阿米卡星加头孢他啶和黏菌素加美罗培南，后一种组合最有效。随后在所有 20 株分离株中测试了黏菌素加美罗培南的疗效。在研究期间，80%的整个 XDR 分离株的细菌密度均显著降低。
这些数据表明，黏菌素加美罗培南可能是治疗 XDR 铜绿假单胞菌感染，包括高风险克隆感染的有效组合，值得在临床试验中进一步评估。
