Background TB treatment is prescribed to millions of individuals yearly, and after cure these individuals often develop recurrent post-TB complications. There is little information exists at the intersection of TB and AMR (i.e., resistance in microbes other than M. tuberculosis complex).The ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) are considered key taxa in AMR acquisition. K. pneumoniae is a common isolate from blood stream infections in our setting, South Africa.

Methods We used the Next-Gen Antimicrobial Resistance Detection (N-GARD) assay, a novel, multiplex, sequencing technique to profile AMR associated strains and genes present in stool of drug-susceptible and drug-resistant TB cases longitudinally.

Results In both cohorts, no significant changes were seen in the proportion of ESKAPE or AMR associated strains during treatment, but trends were noted. The drug-susceptible cohort showed trends of longitudinal increases in AMR-related strains; Enterobacter cloacae, Klebsiella pnemoniae, Klebsiella varicola. Significant longitudinal decreases in AMR-related gyrA (Escherichia coli), fluctuations in tetD, strB and trends of increased FosA, qnrD, qnrA, Sul3 and SaM2 were seen in the drug susceptible cohort. The drug-resistant cohort showed significant increase in npmA and trends of longitudinal increases of ermA and sul1. We also noticed trends of single nucleotide polymorphisms.

Conclusion Overall, the drug-resistant cohort had more significant changes in AMR-associated genes compared to drug susceptible cohort. These changes in the resistome during TB treatment require future investigation and future studies will involve more targeted analysis of identified trends.

Funding: This project is part of the EDCTP2 programme supported by the European Union (grant number TMA2019CDF-2738-ESKAPE-TB) and is partly funded by the National Research Foundation.