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多黏菌素B对脓毒症合并泛耐药革兰阴性菌感染患者的疗效

Efficacy of polymyxin B in septic patients infected with extensively drug-resistant Gram-negative bacteria

    摘要
  • 摘要:
    目的 评估脓毒症合并感染泛耐药（extensively drug-resistant，XDR）革兰阴性菌的患者使用多黏菌素B的疗效。
    方法 回顾性收集2018年8月至2019年7月重症监护室（ICU）收治的30例以多黏菌素B为基础联合抗感染治疗合并XDR脓毒症的数据。记录患者临床特征，细菌感染的部位、种类，使用多黏菌素B的剂量、持续时间，多黏菌素B启动早晚（泛耐药菌培养阳性48 h以内或48 h以后使用多黏菌素B）。主要结局为患者在ICU中死亡。
    结果 共纳入30例患者，其中男性24例，平均年龄为（66.7±18.9）岁，均为多黏菌素B与广谱抗生素静脉联合用药。感染XDR革兰阴性菌患者包括感染肺炎克雷伯菌11例、感染鲍曼不动杆菌11例、感染铜绿假单胞菌3例，感染2种以上耐药菌5例。感染部位分别为血流（13例）、肺部（14例）和导管（3例）。14例（46.6%）患者48 h内启用多黏菌素B，使用多黏菌素B的中位时间为8 d，中位累计剂量为1 115.0 mg。血流感染的细菌转阴率（76.9%）明显高于肺部感染（7.1%）和导管感染（66.7%，P=0.001）。ICU患者死亡率为60.0%（18/30）。多因素分析提示，序贯器官衰竭（SOFA）评分（OR=1.434，95% CI 1.017~2.022，P=0.040）和晚于48 h启用多黏菌素B（OR=12.950，95% CI 1.487~112.770，P=0.020）与ICU死亡密切相关。使用多黏菌素B前36.7%的患者存在慢性肾功能不全；使用多黏菌素B后，急性肾损伤（AKI）患者增至70.0%（χ2=4.27，P=0.039）。
    结论 对于合并感染XDR革兰阴性菌的脓毒症患者，晚启用多黏菌素B与不良预后相关；使用多黏菌素B后，需密切关注药物相关AKI。

     

    Abstract:
    Objective To investigate the clinical efficacy and safety of polymyxin B in septic patients infected with extensively drug-resistant (XDR) Gram-negative bacteria.
    Methods Retrospective data were collected in 30 septic patients with XDR Gram-negative bacterial infection treated with polymyxin B in the intensive care unit from August 2018 to July 2019. Patients' clinical characteristics, bacterial location and type, the total dose and duration of polymyxin B, early or delayed administration of polymyxin B (within or after 48 hours on XDR bacterial were observed) were recorded. The primary endpoint was ICU mortality.
    Results Of the 30 septic patients, 24 (80%) were male, with a mean age of (66.7±18.9) years. All patients received polymyxin B treatment. 11 patients infected with Klebsiella pneumonia, 11 patients infected with Acinetobacter baumannii, 3 patients infected with Pseudomonas aeruginosa, and 5 patients infected with mixed resistant bacteria. The infection sites were bloodstream (13 cases), pulmonary (14 cases), and catheter (3 cases). The median duration of polymyxin B was 8 days, the median cumulative dose was 1 115.0 mg. 14 patients (46.6%) initiated polymyxin B within 48 hours. After the treatment of polymyxin B, the clearance rate (76.9%) of microorganisms in bloodstream was significantly higher than that in pulmonary (7.1%) and catheter (66.7%; P=0.001). ICU mortality rate was 60.0% (18/30). Multivariate analyses showed that sequential organ failure assessment (SOFA) score (OR=1.434, 95% CI 1.017-2.022, P=0.040) and delayed initiation of polymyxin B (OR=12.950, 95% CI 1.487-112.770, P=0.020) were closely related to ICU death. Moreover, 36.7% of patients with polymyxin B had chronic renal insufficiency, and after treatment of polymyxin B, the proportion of acute kidney injury (AKI) increased to 70.0% (χ2=4.27, P=0.039).
    Conclusions Delayed use of polymyxin B-based combination therapy is associated with poor prognosis of septic patients with XDR Gram-negative bacteria. Nephrotoxicity prevalence should be closely monitored in patients treated with polymyxin B.

     

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