Dataset Information

Whole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzania.

ABSTRACT:

Background

Rifampicin- or multidrug-resistant (RR/MDR) Mycobacterium tuberculosis complex (MTBC) strains account for considerable morbidity and mortality globally. WGS-based prediction of drug resistance may guide clinical decisions, especially for the design of RR/MDR-TB therapies.

Methods

We compared WGS-based drug resistance-predictive mutations for 42 MTBC isolates from MDR-TB patients in Tanzania with the MICs of 14 antibiotics measured in the Sensititre™ MycoTB assay. An isolate was phenotypically categorized as resistant if it had an MIC above the epidemiological-cut-off (ECOFF) value, or as susceptible if it had an MIC below or equal to the ECOFF.

Results

Overall, genotypically non-wild-type MTBC isolates with high-level resistance mutations (gNWT-R) correlated with isolates with MIC values above the ECOFF. For instance, the median MIC value (mg/L) for rifampicin-gNWT-R strains was >4.0 (IQR 4.0-4.0) compared with 0.5 (IQR 0.38-0.50) in genotypically wild-type (gWT-S, P < 0.001); isoniazid-gNWT-R >4.0 (IQR 2.0-4.0) compared with 0.25 (IQR 0.12-1.00) among gWT-S (P = 0.001); ethionamide-gNWT-R 15.0 (IQR 10.0-20.0) compared with 2.50 (IQR; 2.50-5.00) among gWT-S (P < 0.001). WGS correctly predicted resistance in 95% (36/38) and 100% (38/38) of the rifampicin-resistant isolates with ECOFFs >0.5 and >0.125 mg/L, respectively. No known resistance-conferring mutations were present in genes associated with resistance to fluoroquinolones, aminoglycosides, capreomycin, bedaquiline, delamanid, linezolid, clofazimine, cycloserine, or p-amino salicylic acid.

Conclusions

WGS-based drug resistance prediction worked well to rule-in phenotypic drug resistance and the absence of second-line drug resistance-mediating mutations has the potential to guide the design of RR/MDR-TB regimens in the future.

SUBMITTER: Mbelele PM

PROVIDER: S-EPMC9021016 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Whole genome sequencing-based drug resistance predictions of multidrug-resistant <i>Mycobacterium tuberculosis</i> isolates from Tanzania.

Mbelele Peter M PM Utpatel Christian C Sauli Elingarami E Mpolya Emmanuel A EA Mutayoba Beatrice K BK Barilar Ivan I Dreyer Viola V Merker Matthias M Sariko Margaretha L ML Swema Buliga M BM Mmbaga Blandina T BT Gratz Jean J Addo Kennedy K KK Pletschette Michel M Niemann Stefan S Houpt Eric R ER Mpagama Stellah G SG Heysell Scott K SK

JAC-antimicrobial resistance 20220421 2

<h4>Background</h4>Rifampicin- or multidrug-resistant (RR/MDR) <i>Mycobacterium tuberculosis</i> complex (MTBC) strains account for considerable morbidity and mortality globally. WGS-based prediction of drug resistance may guide clinical decisions, especially for the design of RR/MDR-TB therapies.<h4>Methods</h4>We compared WGS-based drug resistance-predictive mutations for 42 MTBC isolates from MDR-TB patients in Tanzania with the MICs of 14 antibiotics measured in the Sensititre™ MycoTB assay. ...[more]

PMID: 35465240

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