A Study on Factors Influencing Delayed Sputum Conversion in Newly Diagnosed Pulmonary Tuberculosis Based on Bacteriology and Genomics

Abstract Conversion of sputum from positive to negative is one of the indicators of intensive phase treatment of pulmonary tuberculosis. We analyzed the sputum conversion of 1782 patients diagnosed sputum-positive pulmonary tuberculosis in Beijing between 2021–2022 and designed a case-matched study including 24 pairs of delayed and timely sputum-conversion patients. We collect isolates from delayed-sputum-conversion patients before and after anti-tuberculosis treatment (ATT) and initial isolates of timely-sputum-conversion patients who reported sputum positive only once. 75 strains were conducted drug sensitivity testing (DST) of 13 anti-TB drugs and whole-genome sequencing (WGS) to analyze the risk factors of delayed conversion and the dynamics changes of drug resistance and genomics of MTB during ATT. We found TB patients who achieve sputum negative conversion at the end of 2 months of ATT have better treatment outcomes and whose initial isolates show lower levels of drug resistance. Clinical isolates from delayed conversion patients showed dynamically changing resistance phenotypes and intra-host heterogeneity and changes in dominant pathogenic bacteria. SNP profiles showed large differences between groups. The study provided insight into the bacteriological and genomic variation of delayed-sputum-conversion. It would be helpful for early assessment of sputum conversion and Guidance on anti-tuberculosis treatment.