Alp Emine, Eren Esma, Elay Gülseren, Cevahir Fatma, Esmaoğlu Aliye, Rello Jordi
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Erciyes, Turkey: Infection Control Committee, Faculty of Medicine, Erciyes University, Erciyes, Turkey.
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Erciyes, Turkey.
Infez Med. 2017 Dec 1;25(4):311-319.
Colistin loading dose (LD) has been postulated as an advance in therapy. The clinical, microbiological effectiveness and nephrotoxicity of adding an LD to systemic colistin in ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remain unknown. In this quasi experimental study, the efficacy, outcomes and nephrotoxicity in 30 adults who received intravenous colistin with LD for MDR A. baumannii ventilator associated pneumonia were compared with 22 in absence of LD. Adding LD, the clinical cure rate at 14 days of therapy increased from 47.6% to 56.7% (p>0.397). No significant differences in bacteriological clearance (80 vs 81%), ICU mortality (50% vs 54.2%) or ICU length of stay (median: 32 vs 36 days) were identified. Mortality increased (76.2% vs 35.5%, p=0.004) in patients with nephrotoxicity, with age (median 67.0 vs. 50.0 years, p=0.002) being the only risk factor for nephrotoxicity. The nephrotoxicity rate increased from 27.3% in absence of LD to 35.3% with LD and SOFA <8, and 69.2% (p= 0.065) with LD and SOFA >7. Overall, nephrotoxicity was more severe in the LD group according to RIFLE criteria (p=0.015). Adding LD to systemic colistin for MDR A. baumannii VAP had no significant effect on clinical cure rates, bacteriologic clearance or pre-defined outcomes. However, the nephrotoxicity rate increased with LD, with special risk in adults with high organ failure development or advanced age. Further evidence regarding the risks and benefits of LD is required. The development of newer agents and strategies is urgently needed.
多黏菌素负荷剂量（LD）被认为是治疗方面的一项进展。在由多重耐药（MDR）鲍曼不动杆菌引起的呼吸机相关性肺炎（VAP）中，在全身应用多黏菌素时添加负荷剂量的临床疗效、微生物学有效性及肾毒性尚不清楚。在这项准实验研究中，将30例接受静脉注射多黏菌素负荷剂量治疗MDR鲍曼不动杆菌呼吸机相关性肺炎的成年人的疗效、结局及肾毒性，与22例未接受负荷剂量的成年人进行了比较。添加负荷剂量后，治疗14天时的临床治愈率从47.6%提高到了56.7%（p>0.397）。在细菌清除率（80%对81%）、重症监护病房（ICU）死亡率（50%对54.2%）或ICU住院时间（中位数：32天对36天）方面未发现显著差异。发生肾毒性的患者死亡率增加（76.2%对35.5%，p=0.004），年龄（中位数67.0岁对50.0岁，p=0.002）是肾毒性的唯一危险因素。在序贯器官衰竭评估（SOFA）评分<8时，未使用负荷剂量时肾毒性发生率为27.3%，使用负荷剂量时为35.3%；在SOFA评分>7时，使用负荷剂量时肾毒性发生率为69.2%（p=0.065）。总体而言，根据RIFLE标准，负荷剂量组的肾毒性更严重（p=0.015）。在MDR鲍曼不动杆菌VAP中，在全身应用多黏菌素时添加负荷剂量对临床治愈率、细菌清除率或预先确定的结局没有显著影响。然而，使用负荷剂量时肾毒性发生率增加，在器官功能衰竭进展严重或年龄较大的成年人中风险尤其高。需要更多关于负荷剂量风险和益处的证据。迫切需要开发更新的药物和策略。
