P12
Whole genome sequencing for comprehensive management of Bedaquiline-resistant tuberculosis: a case report
E C Conceicao(1) M Miala(2) B Fanampe(2) F Wells(1) T H Heupink(3) L Verboven(3) L Setlhare(2) A E Ogunbayo(4) N Mhalmbo(4) Z Sibeko(5) F Ndebele(5) S Charalambous(5) G Churchyard(5) A VDS van Dijk(4) R Warren(1) A Van Rie(3)
1:South African Medical Research Council Centre for Tuberculosis Research, DST NRF Centre of Excellence for Biomedical Tuberculosis research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; 2:Free State Department of Health, TB, DR-TB & CDC Directorate, Bloemfontein, South Africa; 3:Tuberculosis Omics ResearCH, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; 4:Universitas Academic Laboratory, National Health Laboratory Service and Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; 5:Aurum Institute, Johannesburg, South Africa
An HIV-positive woman with rifampicin resistant tuberculosis initiated the all oral BDQ-LZD-CFZ-LFX-ETO-PZA-INH(high-dose) regimen. Because of fluoroquinolone resistance on LPA, treatment was changed at month 1 to BDQ-LZD-CFZ-DLM-PAS. Culture conversion was achieved at month 4 but reverted at month 11, whereafter the patient was lost to care. One year later she returned and was initiated on BDQ-CFZ-TZD-LZD-DLM-PAS. Phenotypic BDQ resistance was diagnosed on the month 4 culture. The patient was lost to care at month 5 and represented for care 7 months later. We performed whole genome sequencing and contact tracing. The isolate contained 41 mutations in tier-1 and 20 in tier-2 candidate resistance genes. Resistance was detected for INH (inhA_G-154A), RIF/RBT (rpoB_Ser450Leu), PZA (pncA_Gly97Asp), EMB (embB_Met306Val), LFX/MFX (gyrB_Glu501Asp), BDQ/CFZ (mmpR5/Rv0678_Gln22Pro), ETO (inhA_G-154A) and SM (rrs_C517T). Despite the presence of variants, the isolate was judged susceptible to AMI (fprA-11_-10insA, rrs_C-187T, fprA_C591A, aftB_T-770C, tlyA_A33G), TZD (ald_T-32C, cycA_Arg93Leu, cycA_Ser187Pro, cycA_C-14T, ddlA_Thr365Ala), DLM (fgd1_T960C), and imipenem/meropenem (nadD_A-44C). No variants were detected in candidate resistance genes for LZD and PAS. The patient was hospitalized and initiated on LZD-DLM-PAS-TZD-imipenem and clavulanic acid, received a disability grant and support by a psychologist and social worker. The phylogenetic tree did not identify rifampicin resistant isolates with <12 SNP difference from patients residing in the same province. Contact tracing of five household members and two other close contacts revealed that none had active TB. WGS was valuable in the identification of a rescue treatment regimen and was complementary to contact tracing for assessment of transmission.
Keywords: whole-genome sequencing, bedaquiline-resistant tuberculosis.