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Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections-A Cohort Study.
Antibiotics ( IF 4.3 ) Pub Date : 2020-07-27 , DOI: 10.3390/antibiotics9080451
Yiying Cai 1, 2 , Hui Leck 1 , Ray W Tan 2 , Jocelyn Q Teo 1, 3 , Tze-Peng Lim 1, 4, 5 , Winnie Lee 1 , Maciej Piotr Chlebicki 6 , Andrea L Kwa 1, 5, 7
Affiliation  

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

中文翻译:

高剂量多粘菌素B抵抗碳青霉烯抗革兰氏阴性细菌感染的临床经验-A队列研究。

人群药代动力学研究表明,高剂量多粘菌素B(PMB)(≥30,000IU / kg /天)可以改善对碳青霉烯耐药的革兰氏阴性细菌(CR-GNB)的细菌杀灭。我们旨在描述开高剂量PMB的CR-GNB感染患者的疗效和肾毒性。从2013年至2016年,对患有CR-GNB感染且处方大剂量PMB(〜30,000 IU / kg /天)≥72 h的败血症患者进行了单中心队列研究。研究结果包括30天死亡率和急性肾损伤(AKI)发展。使用多变量回归确定与AKI相关的因素。43例58例CR-GNB患者接受了大剂量P​​MB。57/58(98.3%)CR-GNB易患PMB。高剂量PMB的中位日剂量和持续时间分别为32,051 IU / kg /天(IQR,29,340–34,884 IU / kg /天)和14天(IQR,7–28天)。在7名(16.3%)患者中观察到30天的死亡率。在25例(58.1%)患者中观察到AKI,中位发病期为8天(IQR,6-13天)。每日PMB剂量较高(aOR,1.01; 95%CI,1.00–1.02)和较高数量的并发肾毒素(aOR,2.14; 95%CI; 1.03–4.45)与AKI独立相关。我们观察到,在描述高剂量PMB的CR-GNB患者中有相当一部分会发展为AKI。因此,必须权衡潜在收益与增加的AKI风险。应避免同时使用肾毒素以减少肾毒性。03–4.45)与AKI独立相关。我们观察到,在描述高剂量PMB的CR-GNB患者中,有相当一部分人发展为AKI。因此,必须权衡潜在收益与增加的AKI风险。应避免同时使用肾毒素以减少肾毒性。03–4.45)与AKI独立相关。我们观察到,在描述高剂量PMB的CR-GNB患者中,有相当一部分人发展为AKI。因此,必须权衡潜在收益与增加的AKI风险。应避免同时使用肾毒素以减少肾毒性。
更新日期:2020-07-27
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