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

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dc.contributor.authorMbelele, P.M.
dc.contributor.authorUtpatel, C.
dc.contributor.authorSauli, E.
dc.contributor.authorMpolya, E.A.
dc.contributor.authorAddo, K.K.
dc.contributor.authoret al.
dc.date.accessioned2023-03-09T11:47:30Z
dc.date.available2023-03-09T11:47:30Z
dc.date.issued2022
dc.descriptionResearch Articleen_US
dc.description.abstractAbstract 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.en_US
dc.identifier.otherhttps://doi.org/10.1093/jacamr/dlac042
dc.identifier.urihttp://ugspace.ug.edu.gh:8080/handle/123456789/38746
dc.language.isoenen_US
dc.publisherJAC Antimicrobial Resistanceen_US
dc.subjectmultidrug-resistant Mycobacteriumen_US
dc.subjectdrug resistanceen_US
dc.subjectMycobacteriumen_US
dc.subjecttuberculosisen_US
dc.subjectRifampicinen_US
dc.subjectTanzaniaen_US
dc.titleWhole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzaniaen_US
dc.typeArticleen_US

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