Grignolo Sara, Tatarelli Paola, Guolo Fabio, Minetto Paola, Rivoli Giulia, Guardo Daniela, Del Bono Valerio, Varaldo Riccardo, Gualandi Francesca, Ballerini Filippo, Raiola Annamaria, Gobbi Marco, Viscoli Claudio, Mikulska Malgorzata
Division of Infectious Diseases, Department of Health Sciences (DISSAL), IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Chair of Hematology, Department of Internal Medicine (DiMI), IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Infection. 2017 Aug;45(4):505-511. doi: 10.1007/s15010-017-1010-7. Epub 2017 Mar 28.
Colistin is usually the only drug fully active against multi-drug resistant Gram-negative bacteria, but its nephrotoxicity might limit its use. Recent pharmacokinetic/pharmacodynamic data suggest that high dose of colistin, preceded by a loading dose, are needed to maximize its antibacterial effect. The aim of this study was to determine the safety of high doses colistin, in haematology population.
A retrospective review of haematology patients who received high dose colistin-based therapy in years 2011-2016 was performed. Nephrotoxicity was assessed using RIFLE criteria.
Thirty patients who received 38 courses of colistin were included in the study. Colistin was always administered together with other antibiotics. Colistin was well tolerated, with one case of neurological toxicity and one of cutaneous reaction. There were 22 (58%) treatment cycles without any nephrotoxicity, even though during 16 of these cycles other nephrotoxic drugs were administered. Severe (injury or failure) renal toxicity occurred during 6 (16%) treatment courses, requiring colistin discontinuation in 2 patients and colistin dose reduction in 1. Poorer renal function at baseline and younger age were the only variables associated with increased renal toxicity (p = 0.011 and p = 0.031, respectively). Overall mortality was 18% (7/38) and 29% (11/38) at 7 and 30 days after the treatment onset.
In adult haematology population, high dose colistin therapy is safe and efficacious, despite high frequency of concomitant nephrotoxic treatment.
黏菌素通常是唯一对多重耐药革兰氏阴性菌具有完全活性的药物，但其肾毒性可能会限制其使用。最近的药代动力学/药效学数据表明，需要先给予负荷剂量，然后使用高剂量黏菌素，以使其抗菌效果最大化。本研究的目的是确定高剂量黏菌素在血液学患者群体中的安全性。
对2011年至2016年接受高剂量黏菌素治疗的血液学患者进行回顾性研究。使用RIFLE标准评估肾毒性。
30例接受38个疗程黏菌素治疗的患者纳入研究。黏菌素总是与其他抗生素联合使用。黏菌素耐受性良好，有1例神经毒性和1例皮肤反应。有22个（58%）治疗周期未出现任何肾毒性，尽管在其中16个周期中使用了其他肾毒性药物。6个（16%）治疗疗程出现严重（损伤或衰竭）肾毒性，2例患者需要停用黏菌素，1例患者需要减少黏菌素剂量。基线肾功能较差和年龄较小是与肾毒性增加相关的唯一变量（分别为p = 0.011和p = 0.031）。治疗开始后7天和30天的总死亡率分别为18%（7/38）和29%（11/38）。
在成人血液学患者群体中，尽管联合肾毒性治疗的频率较高，但高剂量黏菌素治疗是安全有效的。
