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Background: To evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for active tuberculosis (TB).

Background: Metagenomic next-generation sequencing (mNGS), with its comprehensiveness, is widely applied in microbiological diagnosis. Etiological diagnosis is of paramount clinical importance in patients with skin and soft tissue infections (SSTIs). However, the clinical application of mNGS in SSTIs is relatively less studied. Materials and methods: From April 1, 2017 to December 31, 2019, 96 SSTI cases were collected. The positive rates of pathogens detected by mNGS and culture were compared by analyzing tissue samples, pus, swabs, and/or interstitial fluids obtained from the infected parts. Modification of the antibiotic treatment strategy due to mNGS was also assessed. Results: The sensitivity of mNGS for detecting pathogens in SSTI cases was superior to that of culture testing (67.7% vs 35.4%; p < 0.01). Significantly higher identification rates for viruses (10.4% vs 0.0%; p < 0.01) and anaerobes (11.5% vs 1.0%; p < 0.01) were obtained with mNGS compared to culture. Of note, rare pathogens such as Vibrio vulnificus and Bartonella henselae were also detected by mNGS. Importantly, the proportion of multi-pathogen SSTIs detected by mNGS was higher than that of multi-pathogen SSTIs detected by culture (16.7% vs 6.3%; p = 0.035). The rate of targeted antibiotic treatment was significantly higher in mNGS-positive cases than in mNGS-negative cases (41.7% vs 3.8%; p < 0.01). In culture-negative and mNGS-positive cases, the improvement rate was higher than that in mNGS-negative cases, but this was not statistically significant (75.0% vs 73.1%; p = 0.864). Conclusions: mNGS is a promising tool for the etiological diagnosis of SSTIs, particularly in identifying viruses, anaerobes, and multi-pathogen infections. The application of mNGS testing in clinical practice could change antibiotic treatment strategies and partly benefit clinical outcomes.