Marmor Meghan, Sharifi Husham, Jacobs Susan, Fazeli Kiana, Ruoss Stephen
Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, United States of America.
Respir Res. 2024 Mar 11;25(1):123. doi: 10.1186/s12931-024-02752-y.
Treatment of Mycobacterium avium complex pulmonary disease (MAC-PD) involves prolonged courses of multiple antibiotics that are variably tolerated and commonly cause adverse drug reactions (ADR). The purpose of this retrospective, single-center study was to identify demographic and disease-related variables associated with significant ADRs among patients treated with antibiotics against MAC-PD.
We reviewed all patients treated with antibiotic therapy for MAC-PD at a single center from 2000 to 2021. Patients were included if they met diagnostic criteria for MAC-PD, were prescribed targeted antibiotic therapy for any length of time and had their treatment course documented in their health record. We compared patients who completed antibiotics as originally prescribed (tolerant) with those whose antibiotic treatment course was modified or terminated secondary to an ADR (intolerant).
Over the study period, 235 patients were prescribed antibiotic treatment with their clinical course documented in our center's electronic health record, and 246 treatment courses were analyzed. One hundred forty-three (57%) tolerated therapy versus 108 (43%) experienced ADRs. Among the 108 intolerant courses, 67 (63%) required treatment modification and 49 (46%) required premature treatment termination. Treatment intolerance was associated more frequently with smear positive sputum cultures (34% vs. 20%, p = 0.009), a higher Charlson Comorbidity Index (CCI) (4 vs. 6, p = 0.007), and existing liver disease (7% vs. 1%, p = 0.03). There was no between-group difference in BMI (21 vs. 22), fibrocavitary disease (24 vs. 19%), or macrolide sensitivity (94 vs. 80%). The use of daily therapy was not associated with intolerance (77 vs. 79%). Intolerant patients were more likely to be culture positive after 6 months of treatment (44 vs. 25%).
Patients prescribed antibiotic therapy for MAC-PD are more likely to experience ADRs if they have smear positive sputum cultures at diagnosis, a higher CCI, or existing liver disease. Our study's rate of early treatment cessation due to ADR's was similar to that of other studies (20%) but is the first of its kind to evaluate patient and disease factors associated with ADR's. A systematic approach to classifying and addressing ADRs for patients undergoing treatment for MAC-PD is an area for further investigation.
鸟分枝杆菌复合群肺病(MAC-PD)的治疗需要长期使用多种抗生素,这些抗生素的耐受性各不相同,且通常会引起药物不良反应(ADR)。这项回顾性单中心研究的目的是确定在接受抗MAC-PD抗生素治疗的患者中,与严重ADR相关的人口统计学和疾病相关变量。
我们回顾了2000年至2021年在单一中心接受抗生素治疗MAC-PD的所有患者。如果患者符合MAC-PD的诊断标准,接受了任何时长的靶向抗生素治疗,且其治疗过程记录在健康记录中,则纳入研究。我们将按原处方完成抗生素治疗的患者(耐受)与因ADR而修改或终止抗生素治疗过程的患者(不耐受)进行了比较。
在研究期间,235例患者接受了抗生素治疗,其临床过程记录在我们中心的电子健康记录中,共分析了246个治疗疗程。143例(57%)耐受治疗,108例(43%)发生ADR。在108个不耐受疗程中,67例(63%)需要修改治疗方案,49例(46%)需要提前终止治疗。治疗不耐受更常与痰涂片阳性培养(34%对20%,p = 0.009)、较高的Charlson合并症指数(CCI)(4对6,p = 0.007)和现有肝病(7%对1%,p = 0.03)相关。两组之间在体重指数(21对22)、纤维空洞性疾病(24%对19%)或大环内酯敏感性(94%对80%)方面无差异。每日治疗的使用与不耐受无关(77%对79%)。不耐受患者在治疗6个月后更可能培养阳性(44%对25%)。
诊断时痰涂片阳性、CCI较高或有现有肝病的MAC-PD患者接受抗生素治疗时更可能发生ADR。我们研究中因ADR导致的早期治疗中断率与其他研究相似(20%),但本研究是首个评估与ADR相关的患者和疾病因素的研究。对于接受MAC-PD治疗的患者,采用系统方法对ADR进行分类和处理是一个需要进一步研究的领域。