Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing.
Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing.
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DOI：
10.1592/phco.30.12.1279
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发表时间：
2010-12
期刊：
影响因子：
4.1
通讯作者：
Tsuji BT
中科院分区：
文献类型：
--
作者：
Lim LM;Ly N;Anderson D;Yang JC;Macander L;Jarkowski A 3rd;Forrest A;Bulitta JB;Tsuji BT
粘菌素是一种多粘菌素抗生素，于20世纪40年代末被发现用于治疗革兰氏阴性感染。经过几年的临床应用，由于有显著的肾毒性和神经毒性的报道，它的受欢迎程度降低了。最近，这种抗生素重新出现，成为铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌等多重耐药生物的最后治疗选择。由于这些革兰氏阴性病原体的高发病率和死亡率，需要覆盖这些革兰氏阴性病原体的抗生素是至关重要的，这使得粘菌素成为非常重要的治疗选择。然而，不幸的是，在病例报告中已经记录了这三种微生物对粘菌素的耐药性。虽然引起粘菌素耐药的确切机制尚未确定，但推测PmrA-pmrB和Phop-PhoQ基因调控系统可能起作用。粘菌素的剂量必须优化，因为粘菌素是最后的治疗选择；此外，次优剂量与耐药性的发展有关。然而，缺乏药代动力学和药效学研究，以及剂量单位没有普遍统一，使得制定粘菌素的最佳剂量方案和具体剂量指南变得困难。在可能有多器官衰竭的危重患者中，肾功能不全可能改变粘菌素的药代动力学。因此，为了达到最大的疗效和最小的毒性，在这一患者群体中改变剂量势在必行。关于粘菌素毒性，大多数研究表明，肾毒性是可逆的，而且没有人们认为的那么频繁，神经毒性很少见。需要进一步的研究来充分了解这两种调控系统对耐药性的影响，以及抑制和克服这些发展模式所需的粘菌素剂量。
Colistin is a polymyxin antibiotic that was discovered in the late 1940s for the treatment of gram-negative infections. After several years of clinical use, its popularity diminished because of reports of significant nephrotoxicity and neurotoxicity. Recently, the antibiotic has resurfaced as a last-line treatment option for multidrug-resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The need for antibiotics with coverage of these gram-negative pathogens is critical because of their high morbidity and mortality, making colistin a very important treatment option. Unfortunately, however, resistance to colistin has been documented among all three of these organisms in case reports. Although the exact mechanism causing colistin resistance has not been defined, it is hypothesized that the PmrA-PmrB and PhoP-PhoQ genetic regulatory systems may play a role. Colistin dosages must be optimized, as colistin is a last-line treatment option; in addition, suboptimal doses have been linked to the development of resistance. The lack of pharmacokinetic and pharmacodynamic studies and no universal harmonization of dose units, however, have made it difficult to derive optimal dosing regimens and specific dosing guidelines for colistin. In critically ill patients who may have multiorgan failure, renal insufficiency may alter colistin pharmacokinetics. Therefore, dosage alterations in this patient population are imperative to achieve maximal efficacy and minimal toxicity. With regard to colistin toxicity, most studies show that nephrotoxicity is reversible and less frequent than once thought, and neurotoxicity is rare. Further research is needed to fully understand the impact that the two regulatory systems have on resistance, as well as the dosages of colistin needed to inhibit and overcome these developing patterns.
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影响因子：
3.7
作者：
Falagas ME;Bliziotis IA;Kasiakou SK;Samonis G;Athanassopoulou P;Michalopoulos A
通讯作者：
Michalopoulos A
影响因子：
3.6
作者：
Gunn, JS;Lim, KB;Miller, SI
通讯作者：
Miller, SI
影响因子：
4.9
作者：
DIXON, RA;CHOPRA, I
通讯作者：
CHOPRA, I
DOI：
10.1016/j.ijantimicag.2009.11.016
发表时间：
2010-03-01
影响因子：
10.8
作者：
Cheng, Chien-Yu;Sheng, Wang-Huei;Chang, Shan-Chwen
通讯作者：
Chang, Shan-Chwen
影响因子：
15.1
作者：
Falagas, Matthew E.;Kasiakou, Sofia K.
通讯作者：
Kasiakou, Sofia K.