Naval Medicine Readiness & Training Command Portsmouth, USA.
Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Pulm Pharmacol Ther. 2021 Oct;70:102058. doi: 10.1016/j.pupt.2021.102058. Epub 2021 Jul 20.
/QUESTION: Nontuberculous mycobacteria (NTM) infections are increasingly detected but difficult to cure given complex drug-resistance patterns. Select U.S. centers have incorporated clofazimine in the treatment of NTM but experience is limited as procurement restrictions hamper widespread use.
A prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection and treated with clofazimine between February 2015 and April 2019 at a tertiary referral hospital. Treatment success was defined by a combined outcome of clinical stabilization, microbiologic cure and radiologic improvement. Secondary outcomes included all-cause mortality and time to sputum culture conversion. Uni/multi-variate regression were used to define associations between pre-determined predictor variables and overall treatment outcome.
Of 44 patients enrolled, 39 (89 %) received clofazimine along with a median of 3 concomitant antibiotics. Thirty-one (80 %) of patients had pulmonary NTM infection, with Mycobacterium abscessus group and Mycobacterium avium complex being the most common species groups identified. Of 36 people with evaluable outcomes, 35 (97 %) survived and 22 (58 %) had treatment success, including 12 of 19 (63 %) with Mycobacterium abscessus group. In multivariate analysis, patients with Mycobacterium abscessus group were more likely to experience treatment success (OR 18.22, 95%CI 0.972-341.43, p = 0.052), while macrolide resistance predicted a lack of treatment success (OR 0.053, 95%CI 0.003-0.841, p = 0.037). Clofazimine was well-tolerated.
Adding clofazimine to multi-class antibiotic regimens for drug-resistant NTM infection led to treatment success in the majority treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within an otherwise optimized drug regimen.
非结核分枝杆菌（NTM）感染的检出率不断增加，但由于耐药模式复杂，治疗难度较大。美国部分中心已将氯法齐明纳入 NTM 治疗方案，但由于采购限制阻碍了其广泛应用，经验有限。
对 2015 年 2 月至 2019 年 4 月期间在一家三级转诊医院诊断为肺部或肺外 NTM 感染并接受氯法齐明治疗的患者进行前瞻性队列研究。治疗成功的定义为临床稳定、微生物学治愈和影像学改善的综合结果。次要结局包括全因死亡率和痰培养转阴时间。采用单变量/多变量回归分析来确定预先确定的预测变量与总体治疗结局之间的关系。
共纳入 44 例患者，其中 39 例（89%）接受了氯法齐明治疗，同时使用中位数为 3 种的联合抗生素。31 例（80%）患者患有肺部 NTM 感染，最常见的菌种为脓肿分枝杆菌组和鸟分枝杆菌复合群。36 例可评估结局的患者中，35 例（97%）存活，22 例（58%）治疗成功，其中脓肿分枝杆菌组 19 例中有 12 例（63%）治疗成功。多变量分析显示，脓肿分枝杆菌组患者更有可能治疗成功（OR 18.22，95%CI 0.972-341.43，p=0.052），而大环内酯类耐药预示着治疗失败（OR 0.053，95%CI 0.003-0.841，p=0.037）。氯法齐明耐受性良好。
在多类抗生素耐药 NTM 感染治疗方案中加入氯法齐明可使大多数患者治疗成功。需要开展随机对照研究以确定氯法齐明在优化药物治疗方案中的单独作用。
