School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China.
The Fifth People's Hospital of Suzhou, Infectious Disease Hospital Affiliated to Soochow University, Suzhou, China.
Int J Infect Dis. 2021 Jul;108:81-88. doi: 10.1016/j.ijid.2021.04.027. Epub 2021 Apr 16.
Although phenotypic drug susceptibility testing (DST) of Mycobacterium tuberculosis (Mtb) takes up to 6-8 weeks, little is known about how drug susceptibility is affected during this period.
We performed a prospective cohort study to investigate the development of drug resistance (DR) during turnaround time (TAT), including 359 pulmonary tuberculosis (PTB) patients with a baseline DST result of an Mtb isolate collected at TB diagnosis and a follow-up DST result of an Mtb isolate collected when baseline DST result was available between 2013 and 2018. Whole-genome sequencing (WGS) was used to differentiate between acquired drug resistance, exogenous reinfection, and mixed infection.
Among the studied patients, during TAT for DST, 116 (32.3%) developed DR to four first-line drugs (rifampicin, isoniazid, pyrazinamide, ethambutol). Among 116 pairs of isolates included for WGS, 21 pairs were classified as acquired drug resistance with single nucleotide polymorphisms (SNPs) differences less than 12. Four pairs with an intermediate SNPs differences displayed minor differences in related genotypes and were assessed as mixed infection. The remaining 91 pairs had high SNPs differences consistent with exogenous reinfection.
The exogenous reinfection of drug-resistant strains played a vital role in the development of DR of Mtb isolates during TAT for DST, highlighting the need for both rapid DST methods and improved infection control.
虽然结核分枝杆菌（Mycobacterium tuberculosis，Mtb）表型药敏试验（drug susceptibility testing，DST）需要 6-8 周的时间，但对于在此期间药敏性如何受到影响的了解甚少。
我们进行了一项前瞻性队列研究，以调查在周转时间（turnaround time，TAT）期间耐药性（drug resistance，DR）的发展情况，共纳入 359 例肺结核（pulmonary tuberculosis，PTB）患者，这些患者在 TB 诊断时采集了 Mtb 分离株的基线 DST 结果，在 2013 年至 2018 年期间基线 DST 结果可用时采集了 Mtb 分离株的随访 DST 结果。全基因组测序（whole-genome sequencing，WGS）用于区分获得性耐药、外源性再感染和混合感染。
在所研究的患者中，在 DST 的 TAT 期间，有 116 例（32.3%）对四种一线药物（利福平、异烟肼、吡嗪酰胺、乙胺丁醇）产生了 DR。在纳入 WGS 的 116 对分离株中，有 21 对被归类为获得性耐药，其单核苷酸多态性（single nucleotide polymorphisms，SNP）差异小于 12。四对具有中间 SNP 差异的分离株显示出相关基因型的微小差异，被评估为混合感染。其余 91 对分离株具有与外源性再感染一致的高 SNP 差异。
在 DST 的 TAT 期间，耐药菌株的外源性再感染在 Mtb 分离株 DR 的发展中起着至关重要的作用，这突出了需要快速 DST 方法和改进感染控制。
