Korhonen Virve, Kivelä Pia, Haanperä Marjo, Soini Hanna, Vasankari Tuula
Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland.
Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.
ERJ Open Res. 2022 Nov 28;8(4). doi: 10.1183/23120541.00214-2022. eCollection 2022 Oct.
Treatment of multidrug-resistant tuberculosis (MDR-TB) is a global challenge requiring long treatment with costly drugs. We assessed treatment combinations, outcome and the utility of whole-genome sequencing (WGS) in MDR-TB cases. Clinical, demographic and microbiological data were obtained of all patients with MDR-TB who started treatment in Finland in 2007-2016. Definitions of MDR, pre-extensively drug-resistant (pre-XDR) and XDR tuberculosis were those applicable at the study period. Treatment outcome was defined according to World Health Organization (WHO) guidelines. isolates were analysed by WGS in addition to routinely performed phenotypic drug susceptibility testing and genotyping. Among the 47 cases, 35 (74%) had a successful treatment outcome. Risk factors for non-successful outcome were Finnish origin and XDR. Almost 90% of our cases had an adverse event for at least one drug. Phenotypic and WGS drug resistance results were fully concordant for isoniazid, fluoroquinolones and amikacin, and >90% concordant for rifampicin, pyrazinamide, kanamycin and capreomycin. >60% of phenotypically ethambutol-susceptible isolates were genotypically resistant. The results of the rifampicin and isoniazid nucleic acid amplification tests (NAATs) performed for the isolates were identical to the WGS results except for three isolates having uncommon resistance mutations not included in the NAATs. WGS did not reveal unexpected clustering. More training is needed for physicians treating MDR-TB, and especially XDR-TB, to improve treatment outcome. Phenotypic drug susceptibility testing was shown to be unreliable for ethambutol. WGS could aid in the selection of optimal treatment regimen in the future.
耐多药结核病（MDR-TB）的治疗是一项全球性挑战，需要使用昂贵药物进行长期治疗。我们评估了MDR-TB病例的治疗组合、治疗结果以及全基因组测序（WGS）的实用性。收集了2007年至2016年在芬兰开始治疗的所有MDR-TB患者的临床、人口统计学和微生物学数据。MDR、广泛耐药结核病（pre-XDR）和XDR结核病的定义均为研究期间适用的定义。治疗结果根据世界卫生组织（WHO）指南进行定义。除了常规进行的表型药物敏感性测试和基因分型外，还通过WGS对分离株进行了分析。在47例病例中，35例（74%）治疗成功。治疗未成功的风险因素是芬兰裔和XDR。我们几乎90%的病例至少对一种药物有不良事件。异烟肼、氟喹诺酮类和阿米卡星的表型和WGS耐药结果完全一致，利福平、吡嗪酰胺、卡那霉素和卷曲霉素的一致性>90%。>60%表型对乙胺丁醇敏感的分离株在基因分型上耐药。对分离株进行的利福平和异烟肼核酸扩增试验（NAATs）结果与WGS结果相同，但有三株分离株具有NAATs未包括的罕见耐药突变除外。WGS未发现意外的聚集情况。治疗MDR-TB尤其是XDR-TB的医生需要更多培训以改善治疗结果。结果表明，表型药物敏感性测试对乙胺丁醇不可靠。WGS未来可能有助于选择最佳治疗方案。
