Department of General Intensive Care Unit, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou City, Zhejiang Province, People's Republic of China.
Department of Clinical Nutrition, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou City, Zhejiang Province, People's Republic of China.
Drug Des Devel Ther. 2024 Jul 30;18:3399-3413. doi: 10.2147/DDDT.S467967. eCollection 2024.
Multidrug-resistant Gram-negative bacteria (MDR-GNB) are becoming increasingly common around the world, with carbapenems frequently serving as a last resort but being threatened by the growing incidence of carbapenemase-producing bacteria. Ceftazidime-avibactam (CAZ/AVI) is a potential agent against MDR-GNB but with limited clinical experience, particularly in critically ill immunosuppressed children.
This study analyzed the use of CAZ/AVI as salvage treatment in severely infected immunosuppressed children from September 2019 to July 2022. Patients with confirmed GNB infection who received CAZ/AVI were matched with patients who received other antibiotics.
Twenty-five critically ill immunosuppressed children treated with CAZ/AVI were included. The majority had hematologic diseases. All patients presented with sepsis in all 30 courses. Septic shock presented in 36.7% of these courses. The primary sites of infection included bloodstream infection (20.0%), skin and skin structure infection (20.0%), intra-abdominal infection (13.3%) and hospital-acquired pneumonia (10.0%). Twelve of the 25 (48.0%) patients had positive microbiological cultures, mainly and , including 5 carbapenem-resistant GNB-infected cases. Fifteen (50.0%) courses presented clinical improvement. For the initial course of each patient, the clinical response rate of the GNB recovered group was significantly higher than that of the group without GNB recovery (66.7% vs 23.1%, = 0.047). The 14-day and 30-day mortality rates were 24.0% and 28.0%, respectively, which were significantly correlated with the absence of GNB recovery ( = 0.004 and 0.024, respectively) and hospital-acquired pneumonia as the primary site of infection ( = 0.001 and 0.006, respectively). There was no significant difference in major outcomes between patients who received CAZ/AVI and matched patients who received other antibiotics.
CAZ/AVI could be considered a salvage strategy for immunosuppressed children with confirmed GNB infection. Caution should be taken when CAZ/AVI is applied to these patients in the absence of GNB recovery.
全球范围内，耐多药革兰氏阴性菌（MDR-GNB）越来越常见，碳青霉烯类药物常作为最后手段，但产碳青霉烯酶细菌的发病率不断上升，对其构成威胁。头孢他啶-阿维巴坦（CAZ/AVI）是一种针对 MDR-GNB 的潜在药物，但临床经验有限，尤其是在重症免疫抑制儿童中。
本研究分析了 2019 年 9 月至 2022 年 7 月间严重感染免疫抑制儿童使用 CAZ/AVI 作为挽救治疗的情况。接受 CAZ/AVI 治疗的确诊 GNB 感染患者与接受其他抗生素治疗的患者进行匹配。
共纳入 25 例接受 CAZ/AVI 治疗的重症免疫抑制儿童。大多数患有血液系统疾病。所有患者在 30 次疗程中均表现为败血症。其中 36.7%的疗程出现感染性休克。感染的主要部位包括血流感染（20.0%）、皮肤和皮肤结构感染（20.0%）、腹腔内感染（13.3%）和医院获得性肺炎（10.0%）。25 例患者中有 12 例（48.0%）的微生物培养呈阳性，主要为 和 ，包括 5 例耐碳青霉烯类 GNB 感染病例。15 例（50.0%）疗程临床改善。对于每位患者的初始疗程，GNB 恢复组的临床反应率明显高于未恢复 GNB 组（66.7% vs 23.1%， = 0.047）。14 天和 30 天的死亡率分别为 24.0%和 28.0%，与未恢复 GNB（ = 0.004 和 0.024）和医院获得性肺炎作为主要感染部位（ = 0.001 和 0.006）显著相关。接受 CAZ/AVI 治疗的患者与接受其他抗生素治疗的匹配患者在主要结局方面无显著差异。
CAZ/AVI 可作为确诊 GNB 感染免疫抑制儿童的挽救策略。在这些患者中，如果 GNB 未恢复，应谨慎使用 CAZ/AVI。
