P39
Whole genome sequencing for multi-drug resistant tuberculosis in a TB referral center in Rome: six years’ experience.
A Cannas(1) O Butera(1) A Mazzarelli(1) F Messina(1) C Massimino(1) MP Parracino(1) G Gualano(1) F Palmieri(1) A Di Caro(1) C Nisii(1) E Girardi(1)
1:National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS
TB control has been effective in reducing multi-drug resistant-TB globally, and larger implementation of new strategies, such as WGS, are needed for further improvement.
This study, based on WGS of MTB strains isolated at our Institute during 6 years (2016-2021), aimed to evaluate the utility of WGS to correctly predict drug resistance improving drug-sensitivity testing in our setting and to contribute to a faster and more accurate therapy regimen, and to further characterize the mutations circulating in Rome area. To our knowledge, this is the first report on MDR-TB in the area, based on WGS.
WGS was performed on 1001 MTB strains consecutively isolated between January 2016 and December 2021 and mutations for prediction of MDR were further characterized.
Prediction of MDR/RR status was found in 50 strains (5%). (5 RR-TB, 34 MDR-TB, 9 pre-XDR-TB, 1 XDR-TB). Resistance to INH was found in 38 of non-MDR cases.
Ser450Leu and Ser315Thr were the more frequent mutations in rpoB and in katG genes respectively, followed by Asp435Val.
High correlation was found between katG mutation and resistance to 0.1 and 0.4 mg/L of INH by pDST.
Discordance between WGS and pDST was found in few strains harboring mutations (Asp435Tyr and Leu430Pro) known for being generally missed by pDST but associated to poor clinical outcome.
The introduction of WGS in our Institute improved diagnostic routine and allowed accurate and timely therapy implementation.