Zaidi S T R, Al Omran S, Al Aithan A S M, Al Sultan M
School of Pharmacy, Faculty of Health Science, University of Tasmania, Hobart, Tas., Australia.
J Clin Pharm Ther. 2014 Jun;39(3):272-6. doi: 10.1111/jcpt.12138. Epub 2014 Mar 5.
Infections due to multidrug-resistant gram-negative bacteria (MDR-GNB) are a significant burden to the healthcare system globally. Colistin is the drug of choice for MDR-GNB and recent studies recommend high doses. This study investigated the safety of low-dose colistin and the relationship of minimum inhibitory concentration (MIC) of colistin with bacterial cure in the treatment for MDR-GNB infections.
Computerized dispensing records identified all patients who received colistin during January 2010 and December 2011. Patients who were aged < 12 years old, who received colistin for < 72 h or had moderate to severe renal impairment were excluded. Medical records of the remaining patients were reviewed for the necessary data to determine the bacterial cure and nephrotoxicity of colistin. Multivariate logistic regression analysis was used to determine the predictors of bacterial cure.
A total of 125 evaluable patients received colistin during the study period. Ninety-four of 125 (75·2%) patients achieved bacterial cure. No statistically significant differences were observed between patients who achieved and failed to achieve bacterial cure with regards to age, gender, site of infection, mg/kg dose or duration of colistin use. The average MIC in the bacterial cure group was significantly lower than the MIC in the bacterial failure group (P = 0·002). Similarly, 30-day mortality from the last dose of colistin was significantly lower in the bacterial cure group (P = 0·002). Nephrotoxicity occurred in 12·8% of patients and was not associated with the dose of colistin or concomitant use of nephrotoxic medications. MIC of <1 μg/mL was the only significant independent predictor of bacterial cure in the multivariate logistic regression analysis (P = 0·015), whereas infection caused by MDR Klebsiella pneumonia was an independent risk factor for bacterial failure (P = 0·049).
Low-dose colistin is an effective option in the treatment for infections caused by MDR-GNB with a low incidence of nephrotoxicity. Patients who achieved bacterial cure had significantly lower MIC values of colistin against MDR-GNB than those who failed to achieve it. Colistin dose should be based on the MIC data of a given patient or local antimicrobial sensitivity data to maximize its efficacy.
耐多药革兰氏阴性菌（MDR - GNB）感染给全球医疗系统带来了沉重负担。黏菌素是治疗MDR - GNB的首选药物，近期研究推荐使用高剂量。本研究调查了低剂量黏菌素的安全性以及黏菌素最低抑菌浓度（MIC）与MDR - GNB感染治疗中细菌清除的关系。
通过计算机化配药记录确定2010年1月至2011年12月期间所有接受黏菌素治疗的患者。排除年龄小于12岁、接受黏菌素治疗时间小于72小时或有中度至重度肾功能损害的患者。查阅其余患者的病历以获取确定黏菌素细菌清除率和肾毒性所需的数据。采用多因素逻辑回归分析确定细菌清除的预测因素。
在研究期间，共有125例可评估患者接受了黏菌素治疗。125例患者中有94例（75.2%）实现了细菌清除。在实现和未实现细菌清除的患者之间，在年龄、性别、感染部位、mg/kg剂量或黏菌素使用时长方面未观察到统计学上的显著差异。细菌清除组的平均MIC显著低于细菌清除失败组（P = 0.002）。同样，细菌清除组最后一剂黏菌素后30天的死亡率显著更低（P = 0.002）。12.8%的患者发生了肾毒性，且与黏菌素剂量或肾毒性药物的联合使用无关。在多因素逻辑回归分析中，MIC <1 μg/mL是细菌清除的唯一显著独立预测因素（P = 0.015），而耐多药肺炎克雷伯菌引起的感染是细菌清除失败的独立危险因素（P = 0.049）。
低剂量黏菌素是治疗MDR - GNB感染的有效选择，肾毒性发生率低。实现细菌清除的患者对MDR - GNB的黏菌素MIC值显著低于未实现细菌清除的患者。黏菌素剂量应基于特定患者的MIC数据或当地抗菌药物敏感性数据，以使其疗效最大化。
