内科理论与实践

内科理论与实践 ›› 2024, Vol. 19 ›› Issue (01): 51-56.doi: 10.16138/j.1673-6087.2024.01.09

• 论著 • 上一篇    下一篇

复方磺胺甲噁唑血药峰浓度测定对治疗非人类免疫缺陷病毒感染患者耶氏肺孢子菌肺炎的临床意义

舒扬1a,2, 贺晓双1a, $\boxed{\hbox{陈虹}}$1b, 时国朝1b, 方洁1a()   

  1. 1.上海交通大学医学院附属瑞金医院a.药剂科;b.呼吸与危重症医学科 上海交通大学医学院呼吸病研究所，上海 200025
    2.上海交通大学医学院附属新华医院临床药学部，上海 200092
  • 收稿日期:2023-09-15 出版日期:2024-02-29 发布日期:2024-04-28
  • 通讯作者: 方洁 E-mail:fj40517@rjh.com.cn
  • 基金资助:
    上海市2021年度“科技创新行动计划”扬帆计划项目(21YF1426400)

Clinical significance of plasma peak concentration determination of compound sulfamethoxazole in treatment of Pneumocystis jirovecii pneumonia in patients with non-human immunodeficiency virus infection

SHU Yang1a,2, HE Xiaoshuang1a, $\boxed{\hbox{CHEN Hong}}$1b, SHI Guochao1b, FANG Jie1a()   

  1. 1.a. Department of Pharmacy, b. Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2. Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Received:2023-09-15 Online:2024-02-29 Published:2024-04-28
  • Contact: FANG Jie E-mail:fj40517@rjh.com.cn

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摘要：

目的: 探索监测复方磺胺甲噁唑（sulfamethoxazole complex, SMZco）中SMZ血药峰浓度对接受SMZco片治疗的非人类免疫缺陷病毒（immunodeficiency virus， HIV）感染患者耶氏肺孢子菌肺炎（Pneumocystis jirovecii pneumonia，PJP）疗效和安全性的指导意义。方法: 采集2019年1月至2023年5月在瑞金医院住院治疗的非HIV PJP患者的临床数据，回顾性分析患者SMZ血药峰浓度与疗效和不良反应发生情况的关系。结果: 共纳入47例患者，SMZ的血药峰浓度范围为87.49~334.31 mg/L，中位数（四分位间距）为168.62（79.72） mg/L，64%的患者血药峰浓度>150 mg/L。患者30 d全因死亡率为28%，治疗阳性反应率为66%。其中，SMZ血药峰浓度≤150 mg/L患者与>150 mg/L患者30 d全因死亡和治疗阳性反应率差异无统计学意义。29例（62%）患者发生不良反应。相比SMZ血药峰浓度≤150 mg/L的患者，>150 mg/L的患者血小板减少（40%比6%，P=0.025）和血红蛋白降低（37%比0，P=0.013）等不良反应发生率更高，且严重不良反应的发生率更高（43%比12%，P=0.026）。结论: SMZco片用于治疗非HIV PJP患者时，SMZ血药峰浓度≤150 mg/L的患者较>150 mg/L的患者可获得相当的疗效，且发生严重不良反应的风险更小，建议该类患者常规监测SMZ血药峰浓度。

关键词: 耶氏肺孢子菌肺炎, 磺胺甲噁唑, 血药浓度监测, 不良反应

Abstract:

Objective To explore the significance of monitoring the blood peak concentration of sulfamethoxazole (SMZ) to learn the efficacy and safety of compound SMZ (SMZco) tablets in the treatment of Pneumocystis jirovecii pneumonia (PJP) in patients with non-human immunodeficiency virus (HIV). Methods Clinical data of PJP infected patients with non-HIV hospitalized in Ruijin Hospital, from January 2019 to May 2023 were enrollled, and the relationship between the peak plasma concentration of SMZ and the efficacy and occurrence of adverse reactions was retrospectively analyzed. Results A total of 47 patients were included in this study. The peak plasma concentration of SMZ ranged from 87.49 mg/L to 334.31 mg/L, the median (interquartile distance) was 168.62 (79.72) mg/L, and the peak plasma concentration in 64% of patients was >150 mg/L. The 30-day all-cause mortality of the patients was 28%，and the positive response rate was 66%. Among them, there was no statistical difference in 30-day all-cause death and treatment positive response rate between the patients with peak concentration ≤150 mg/L and the patients with peak concentration of SMZ >150 mg/L. In terms of safety, a total of 29 (62%) patients showed adverse reactions. The incidence of thrombocytopenia (40% vs 6%, P=0.025), decreased hemoglobin (37% vs 0, P=0.013) and serious adverse reactions (43% vs 12%, P=0.026) were higher in the patients with SMZ peak concentration >150 mg/L than those in the patients with SMZ peak concentration <150 mg/L. The incidence of serious adverse reactions was higher in the patients with a peak concentration of SMZco >150 mg/L. Conclusions The results of the study showed that as SMZco tablets were used in the treatment of non-HIV patients infected with PJP, those with a peak plasma concentration ≤150 mg/L of SMZ could achieve comparable efficacy, and their risk of serious adverse reactions was less than that of the patients with a peak plasma concentration >150 mg/L. It is suggested that the plasma peak concentration of SMZ should be monitored regularly.

Key words: Pneumocystis yerbii pneumonia, Sulfamethoxazole, Blood concentration monitoring, Adverse reaction

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