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2. Towards clinical breakpoints for non-tuberculous mycobacteria – Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution

Author

Fröberg, Gabrielle, Maurer, Florian P., Chryssanthou, Erja, Fernström, Louise, Benmansour, Hanaa, Boarbi, Samira, Mengshoel, Anne Torunn, Keller, Peter Michael, Viveiros, Miguel, Machado, Diana, Fitzgibbon, Margaret M., Mok, Simone, Werngren, Jim, Cirillo, Daniela Maria, Alcaide, Fernando, Hyyryläinen, Hanne-Leena, Aubry, Alexandra, Andres, Sönke, Nadarajan, Darshaalini, Svensson, Erik, Turnidge, John, Giske, Christian G., Kahlmeter, Gunnar, Cambau, Emmanuelle, van Ingen, Jakko, and Schön, Thomas

Published
2023
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3. Investigation of genomic mutations and their association with phenotypic resistance to new and repurposed drugs in Mycobacterium tuberculosis complex clinical isolates.

Author

Mok, Simone, Roycroft, Emma, Flanagan, Peter R, Wagener, Johannes, and Fitzgibbon, Margaret M

Subjects
MYCOBACTERIUM tuberculosis, PHENOTYPES, GENETIC mutation, GENOTYPES, KNOWLEDGE base, LINEZOLID
Abstract

Background WGS has the potential to detect resistance-associated mutations and guide treatment of MDR TB. However, the knowledge base to confidently interpret mutations associated with the new and repurposed drugs is sparse, and phenotypic drug susceptibility testing is required to detect resistance. Methods We screened 900 Mycobacterium tuberculosis complex genomes from Ireland, a low TB incidence country, for mutations in 13 candidate genes and assessed their association with phenotypic resistance to bedaquiline, clofazimine, linezolid, delamanid and pretomanid. Results We identified a large diversity of mutations in the candidate genes of 195 clinical isolates, with very few isolates associated with phenotypic resistance to bedaquiline (n  = 4), delamanid (n  = 4) and pretomanid (n  = 2). We identified bedaquiline resistance among two drug-susceptible TB isolates that harboured mutations in Rv0678. Bedaquiline resistance was also identified in two MDR-TB isolates harbouring Met146Thr in Rv0678 , which dated back to 2007, prior to the introduction of bedaquiline. High-level delamanid resistance was observed in two isolates with deletions in ddn , which were also resistant to pretomanid. Delamanid resistance was detected in two further isolates that harboured mutations in fbiA , but did not show cross-resistance to pretomanid. All isolates were susceptible to linezolid and clofazimine, and no mutations found were associated with resistance. Conclusions More studies that correlate genotypic and phenotypic drug susceptibility data are needed to increase the knowledge base of mutations associated with resistance, in particular for pretomanid. Overall, this study contributes to the development of future mutation catalogues for M. tuberculosis complex isolates [ABSTRACT FROM AUTHOR]

Published
2023
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4. Origin and Global Expansion of Complex Lineage 3

Author

Shuaib, Yassir A, Utpatel, Christian, Kohl, Thomas A, Barilar, Ivan, Diricks, Margo, Ashraf, Nadia, Wieler, Lothar H, Kerubo, Glennah, Mesfin, Eyob A, Diallo, Awa Ba, Al-Hajoj, Sahal, Ndung'u, Perpetua, Fitzgibbon, Margaret M, Vaziri, Farzam, Sintchenko, Vitali, Martinez, Elena, Viegas, Sofia O, Zhou, Yang, Azmy, Aya, Al-Amry, Khaled, Godreuil, Sylvain, Varma-Basil, Mandira, Narang, Anshika, Ali, Solomon, Beckert, Patrick, Dreyer, Viola, Kabwe, Mwila, Bates, Matthew, Hoelscher, Michael, Rachow, Andrea, Gori, Andrea, Tekwu, Emmanuel M, Sidze, Larissa K, Jean-Paul, Assam A, Beng, Veronique P, Ntoumi, Francine, Frank, Matthias, Diallo, Aissatou Gaye, Mboup, Souleymane, Tessema, Belay, Beyene, Dereje, Khan, Sadiq N, Diel, Roland, Supply, Philip, Maurer, Florian P, Hoffmann, Harald, Niemann, Stefan, and Merker, Matthias

Subjects
C500 Microbiology
Abstract

complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.

Published
2022

5. Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Author

Shuaib, Yassir A., primary, Utpatel, Christian, additional, Kohl, Thomas A., additional, Barilar, Ivan, additional, Diricks, Margo, additional, Ashraf, Nadia, additional, Wieler, Lothar H., additional, Kerubo, Glennah, additional, Mesfin, Eyob A., additional, Diallo, Awa Ba, additional, Al-Hajoj, Sahal, additional, Ndung’u, Perpetua, additional, Fitzgibbon, Margaret M., additional, Vaziri, Farzam, additional, Sintchenko, Vitali, additional, Martinez, Elena, additional, Viegas, Sofia O., additional, Zhou, Yang, additional, Azmy, Aya, additional, Al-Amry, Khaled, additional, Godreuil, Sylvain, additional, Varma-Basil, Mandira, additional, Narang, Anshika, additional, Ali, Solomon, additional, Beckert, Patrick, additional, Dreyer, Viola, additional, Kabwe, Mwila, additional, Bates, Matthew, additional, Hoelscher, Michael, additional, Rachow, Andrea, additional, Gori, Andrea, additional, Tekwu, Emmanuel M., additional, Sidze, Larissa K., additional, Jean-Paul, Assam A., additional, Beng, Veronique P., additional, Ntoumi, Francine, additional, Frank, Matthias, additional, Diallo, Aissatou Gaye, additional, Mboup, Souleymane, additional, Tessema, Belay, additional, Beyene, Dereje, additional, Khan, Sadiq N., additional, Diel, Roland, additional, Supply, Philip, additional, Maurer, Florian P., additional, Hoffmann, Harald, additional, Niemann, Stefan, additional, and Merker, Matthias, additional

Published
2022
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7. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis

Author

Walker, Timothy M, primary, Miotto, Paolo, additional, Köser, Claudio U, additional, Fowler, Philip W, additional, Knaggs, Jeff, additional, Iqbal, Zamin, additional, Hunt, Martin, additional, Chindelevitch, Leonid, additional, Farhat, Maha R, additional, Cirillo, Daniela Maria, additional, Comas, Iñaki, additional, Posey, James, additional, Omar, Shaheed V, additional, Peto, Timothy EA, additional, Suresh, Anita, additional, Uplekar, Swapna, additional, Laurent, Sacha, additional, Colman, Rebecca E, additional, Nathanson, Carl-Michael, additional, Zignol, Matteo, additional, Walker, Ann Sarah, additional, Crook, Derrick W, additional, Ismail, Nazir, additional, Rodwell, Timothy C, additional, Walker, A Sarah, additional, Steyn, Adrie J C, additional, Lalvani, Ajit, additional, Baulard, Alain, additional, Christoffels, Alan, additional, Mendoza-Ticona, Alberto, additional, Trovato, Alberto, additional, Skrahina, Alena, additional, Lachapelle, Alexander S, additional, Brankin, Alice, additional, Piatek, Amy, additional, Gibertoni Cruz, Ana, additional, Koch, Anastasia, additional, Cabibbe, Andrea Maurizio, additional, Spitaleri, Andrea, additional, Brandao, Angela P, additional, Chaiprasert, Angkana, additional, Barbova, Anna, additional, Van Rie, Annelies, additional, Ghodousi, Arash, additional, Bainomugisa, Arnold, additional, Mandal, Ayan, additional, Roohi, Aysha, additional, Javid, Babak, additional, Zhu, Baoli, additional, Letcher, Brice, additional, Rodrigues, Camilla, additional, Nimmo, Camus, additional, NATHANSON, Carl-Michael, additional, Duncan, Carla, additional, Coulter, Christopher, additional, Utpatel, Christian, additional, Liu, Chunfa, additional, Grazian, Clara, additional, Kong, Clare, additional, Wilson, Daniel J, additional, Matias, Daniela, additional, Jorgensen, Danielle, additional, Zimenkov, Danila, additional, Chetty, Darren, additional, Moore, David AJ, additional, Clifton, David A, additional, van Soolingen, Dick, additional, Liu, Dongxin, additional, Kohlerschmidt, Donna, additional, Barreira, Draurio, additional, Ngcamu, Dumisani, additional, Santos Lazaro, Elias David, additional, Kelly, Ellis, additional, Borroni, Emanuele, additional, Roycroft, Emma, additional, Andre, Emmanuel, additional, Böttger, Erik C, additional, Robinson, Esther, additional, Menardo, Fabrizio, additional, Mendes, Flavia F, additional, Jamieson, Frances B, additional, Coll, Francesc, additional, Gao, George Fu, additional, Kasule, George W, additional, Rossolini, Gian Maria, additional, Rodger, Gillian, additional, Smith, E Grace, additional, Meintjes, Graeme, additional, Thwaites, Guy, additional, Hoffmann, Harald, additional, Albert, Heidi, additional, Cox, Helen, additional, Laurenson, Ian F, additional, Arandjelovic, Irena, additional, Barilar, Ivan, additional, Robledo, Jaime, additional, Millard, James, additional, Johnston, James, additional, Posey, Jamie, additional, Andrews, Jason R, additional, Gardy, Jennifer, additional, Guthrie, Jennifer, additional, Taylor, Jill, additional, Werngren, Jim, additional, Metcalfe, John, additional, Coronel, Jorge, additional, Shea, Joseph, additional, Carter, Joshua, additional, Pinhata, Juliana MW, additional, Kus, Julianne V, additional, Todt, Katharina, additional, Holt, Kathryn, additional, Nilgiriwala, Kayzad S, additional, Ghisi, Kelen T, additional, Malone, Kerri M, additional, Faksri, Kiatichai, additional, Musser, Kimberlee A, additional, Joseph, Lavania, additional, Rigouts, Leen, additional, Jarrett, Lisa, additional, Grandjean, Louis, additional, Ferrazoli, Lucilaine, additional, Rodrigues, Mabel, additional, Farhat, Maha, additional, Schito, Marco, additional, Fitzgibbon, Margaret M, additional, Loembé, Marguerite Massinga, additional, Wijkander, Maria, additional, Ballif, Marie, additional, Rabodoarivelo, Marie-Sylvianne, additional, Mihalic, Marina, additional, WILCOX, Mark, additional, ZIGNOL, Matteo, additional, Merker, Matthias, additional, Egger, Matthias, additional, O'Donnell, Max, additional, Caws, Maxine, additional, Wu, Mei-Hua, additional, Whitfield, Michael G, additional, Inouye, Michael, additional, Mansjö, Mikael, additional, Dang Thi, Minh Ha, additional, Joloba, Moses, additional, Kamal, SM Mostofa, additional, Okozi, Nana, additional, ISMAIL, Nazir, additional, Mistry, Nerges, additional, Hoang, Nhung N, additional, Rakotosamimanana, Niaina, additional, Paton, Nicholas I, additional, Rancoita, Paola M V, additional, Lapierre, Pascal, additional, Hall, Patricia J, additional, Tang, Patrick, additional, Claxton, Pauline, additional, Wintringer, Penelope, additional, Keller, Peter M, additional, Thai, Phan Vuong Khac, additional, Supply, Philip, additional, Srilohasin, Prapaporn, additional, Suriyaphol, Prapat, additional, Rathod, Priti, additional, Kambli, Priti, additional, Groenheit, Ramona, additional, Ong, Rick Twee-Hee, additional, Warren, Robin M, additional, Wilkinson, Robert J, additional, Diel, Roland, additional, Oliveira, Rosangela S, additional, Khot, Rukhsar, additional, Jou, Ruwen, additional, Tahseen, Sabira, additional, Gharbia, Saheer, additional, Kouchaki, Samaneh, additional, Shah, Sanchi, additional, Plesnik, Sara, additional, Earle, Sarah G, additional, Dunstan, Sarah, additional, Hoosdally, Sarah J, additional, Mitarai, Satoshi, additional, Gagneux, Sebastien, additional, Yao, Shen-Yuan, additional, Grandjean Lapierre, Simon, additional, Battaglia, Simone, additional, Niemann, Stefan, additional, Pandey, Sushil, additional, Halse, Tanya A, additional, Cohen, Ted, additional, Cortes, Teresa, additional, Prammananan, Therdsak, additional, Kohl, Thomas A, additional, Thuong, Nguyen T T, additional, Teo, Tik Ying, additional, Peto, Timothy E A, additional, William, Timothy, additional, Walker, Timothy M, additional, Rogers, Thomas R, additional, Surve, Utkarsha, additional, Mathys, Vanessa, additional, Furió, Victoria, additional, Cook, Victoria, additional, Vijay, Srinivasan, additional, Escuyer, Vincent, additional, Dreyer, Viola, additional, Sintchenko, Vitali, additional, Saphonn, Vonthanak, additional, Solano, Walter, additional, Lin, Wan-Hsuan, additional, van Gemert, Wayne, additional, He, Wencong, additional, Yang, Yang, additional, Zhao, Yanlin, additional, Qin, Youwen, additional, Xiao, Yu-Xin, additional, Hasan, Zahra, additional, and Puyen, Zully M, additional

Published
2022
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10. False detection of rifampicin resistance using Xpert® MTB/RIF Ultra assay due to an A451V mutation in Mycobacterium tuberculosis

Author

Fitzgibbon, Margaret M, primary, Roycroft, Emma, additional, Sheehan, Gerard, additional, Mc Laughlin, Anne-Marie, additional, Quintyne, Keith Ian, additional, Brabazon, Elaine, additional, O’Meara, Mary, additional, Flanagan, Peter R, additional, Seagar, A -Louise, additional, Laurenson, Ian F, additional, Keane, Joseph, additional, and Rogers, Thomas R, additional

Published
2021
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16. Investigation of Reduced Susceptibility to Glycopeptides among Methicillin-Resistant Staphylococcus aureusIsolates from Patients in Ireland and Evaluation of Agar Screening Methods for Detection of Heterogeneously Glycopeptide-Intermediate S. aureus

Author

Fitzgibbon, Margaret M., Rossney, Angela S., and O'Connell, Brian

Abstract

ABSTRACTMethicillin-resistant Staphylococcus aureus(MRSA) isolates (n= 3,189) from 2,990 patients were investigated by agar screening and by the Etest macromethod for reduced susceptibility to glycopeptide. No vancomycin-resistant S. aureusor glycopeptide-intermediate S. aureus(GISA) isolates were detected, but 178 isolates were confirmed as hetero-GISA (hGISA) by vancomycin population analysis profile (vPAP)-area under the curve (AUC) ratio determination and/or teicoplanin PAP (tPAP) methods. Of 139 isolates detected using the recommended Etest macromethod cutoff values of =8 mg/liter for both vancomycin and teicoplanin or =12 mg/liter for teicoplanin alone, 73 were confirmed as hGISA by vPAP-AUC, 95 were confirmed as hGISA by tPAP, and 108 were confirmed as hGISA by both methods. An Etest macromethod cutoff value of 8 mg/liter for teicoplanin alone detected a further 70 hGISA (17 were confirmed by vPAP-AUC and 70 were confirmed by tPAP). Agar screening utilizing brain heart infusion (BHI) agar containing 6 mg of vancomycin/liter (BHIV6) and Mueller-Hinton (MH) agar containing 8 mg of teicoplanin/liter (MHT8) failed to detect hGISA. MH agar containing 5 mg of teicoplanin/liter (MHT5) and BHI containing 5 mg of teicoplanin/liter (BHIT5) were evaluated using 10-µl volumes of three inoculum concentrations (with densities equivalent to 0.5 and 2.0 McFarland turbidity standards and stationary-phase BHI broth subcultures [MHT50.5, MHT52.0, MHT5S, BHIT50.5, BHIT52.0, and BHIT5S]). The sensitivity of all methods except MHT50.5and MHT52.0was 100%. The specificity ranged from 4 to 82%. BHIT50.5yielded the best performance, with a specificity of 84% for detecting isolates with teicoplanin Etest macromethod values of =8 mg/liter. Screening on BHIT50.5is useful where screen-positive isolates are investigated with the Etest macromethod and confirmed by vPAP-AUC and tPAP. The prevalence of hGISA among patients with blood culture isolates recovered in Irish hospitals between 1999 and 2003 was 2.6%, whereas the prevalence among patients with isolates from all specimen sites collected during a 2-week survey in 1999 was 12%. The prevalence in one hospital decreased from 5.3% in 2003 to 1.5% in 2004.

Published
2007
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17. The Emergence and Importation of Diverse Genotypes of Methicillin-Resistant Staphylococcus aureus(MRSA) Harboring the Panton-Valentine Leukocidin Gene (pvl) Reveal that pvlIs a Poor Marker for Community-Acquired MRSA Strains in Ireland

Author

Rossney, Angela S., Shore, Anna C., Morgan, Pamela M., Fitzgibbon, Margaret M., O'Connell, Brian, and Coleman, David C.

Abstract

ABSTRACTCommunity-acquired methicillin-resistant Staphylococcus aureus(CA-MRSA) carrying pvlis an emerging problem worldwide. CA-MRSA tends to harbor staphylococcal cassette chromosome mectype IV (SCCmecIV), to be non-multiantibiotic resistant, and to have different genotypes from the local hospital-acquired MRSA (HA-MRSA). However, in Ireland, 80% of HA-MRSA isolates have the non-multiantibiotic-resistant genotype ST22-MRSA-IV. This study investigated MRSA isolates from Ireland (CA-MRSA, health care-associated MRSA, and HA-MRSA) for the carriage of pvland determined the genotypic characteristics of all pvl-positive isolates identified. All 1,389 MRSA isolates were investigated by antibiogram-resistogram typing and SmaI DNA macrorestriction analysis. pvl-positive isolates were further characterized by multilocus sequence typing and SCCmec, agr, and toxin gene typing. Twenty-five (1.8%) MRSA isolates belonging to six genotypes (ST30, ST8, ST22, ST80, ST5, and ST154) harbored pvl. Nineteen of these (76%) were CA-MRSA isolates, but a prospective study of MRSA isolates from 401 patients showed that only 6.7% (2/30) of patients with CA-MRSA yielded pvl-positive isolates. Thus, pvlcannot be used as a sole marker for CA-MRSA. Fifty-two percent of pvl-positive MRSA isolates were recovered from patients with skin and soft tissue infections; thirty-six percent were from patients of non-Irish ethnic origin, reflecting the increasing heterogeneity of the Irish population due to immigration. All 25 pvl-positive isolates carried SCCmecIV; 14 (56%) harbored SCCmecIV.1 or IV.3, and the remaining 11 isolates could not be subtyped. This study demonstrates that pvlis not a reliable marker for CA-MRSA in Ireland and reveals the emergence and importation of diverse genotypes of pvl-positive MRSA in Ireland.

Published
2007
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18. Genomic Analysis of Mycobacterium abscessusComplex Isolates Collected in Ireland between 2006 and 2017

Author

Redondo, Natalia, Mok, Simone, Montgomery, Lorraine, Flanagan, Peter R., McNamara, Eleanor, Smyth, Edmond G., O'Sullivan, Niamh, Schaffer, Kirsten, Rogers, Thomas R., and Fitzgibbon, Margaret M.

Abstract

Members of the Mycobacterium abscessuscomplex (MABC) are multidrug-resistant nontuberculous mycobacteria and cause opportunistic pulmonary infections in individuals with cystic fibrosis (CF). In this study, genomic analysis of MABC isolates was performed to gain greater insights into the epidemiology of circulating strains in Ireland. Whole-genome sequencing (WGS) was performed on 70 MABC isolates that had been referred to the Irish Mycobacteria Reference Laboratory between 2006 and 2017 across nine Irish health care centers.

Published
2020
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19. Origin and Global Expansion of Complex Lineage 3.

Author

Shuaib, Yassir A, Utpatel, Christian, Kohl, Thomas A, Barilar, Ivan, Diricks, Margo, Ashraf, Nadia, Wieler, Lothar H, Kerubo, Glennah, Mesfin, Eyob A, Diallo, Awa Ba, Al-Hajoj, Sahal, Ndung'u, Perpetua, Fitzgibbon, Margaret M, Vaziri, Farzam, Sintchenko, Vitali, Martinez, Elena, Viegas, Sofia O, Zhou, Yang, Azmy, Aya, Al-Amry, Khaled, Godreuil, Sylvain, Varma-Basil, Mandira, Narang, Anshika, Ali, Solomon, Beckert, Patrick, Dreyer, Viola, Kabwe, Mwila, Bates, Matthew, Hoelscher, Michael, Rachow, Andrea, Gori, Andrea, Tekwu, Emmanuel M, Sidze, Larissa K, Jean-Paul, Assam A, Beng, Veronique P, Ntoumi, Francine, Frank, Matthias, Diallo, Aissatou Gaye, Mboup, Souleymane, Tessema, Belay, Beyene, Dereje, Khan, Sadiq N, Diel, Roland, Supply, Philip, Maurer, Florian P, Hoffmann, Harald, Niemann, Stefan, Merker, Matthias, Shuaib, Yassir A, Utpatel, Christian, Kohl, Thomas A, Barilar, Ivan, Diricks, Margo, Ashraf, Nadia, Wieler, Lothar H, Kerubo, Glennah, Mesfin, Eyob A, Diallo, Awa Ba, Al-Hajoj, Sahal, Ndung'u, Perpetua, Fitzgibbon, Margaret M, Vaziri, Farzam, Sintchenko, Vitali, Martinez, Elena, Viegas, Sofia O, Zhou, Yang, Azmy, Aya, Al-Amry, Khaled, Godreuil, Sylvain, Varma-Basil, Mandira, Narang, Anshika, Ali, Solomon, Beckert, Patrick, Dreyer, Viola, Kabwe, Mwila, Bates, Matthew, Hoelscher, Michael, Rachow, Andrea, Gori, Andrea, Tekwu, Emmanuel M, Sidze, Larissa K, Jean-Paul, Assam A, Beng, Veronique P, Ntoumi, Francine, Frank, Matthias, Diallo, Aissatou Gaye, Mboup, Souleymane, Tessema, Belay, Beyene, Dereje, Khan, Sadiq N, Diel, Roland, Supply, Philip, Maurer, Florian P, Hoffmann, Harald, Niemann, Stefan, and Merker, Matthias

Abstract

complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.

20. False detection of rifampicin resistance using Xpert ® MTB/RIF Ultra assay due to an A451V mutation in Mycobacterium tuberculosis .

Author

Fitzgibbon MM, Roycroft E, Sheehan G, Mc Laughlin AM, Quintyne KI, Brabazon E, O'Meara M, Flanagan PR, Seagar AL, Laurenson IF, Keane J, and Rogers TR

Abstract

Background: In a 12 month period, three Irish-born adult cases with pulmonary TB were initially diagnosed by Xpert ® MTB/RIF Ultra assay, which detected a rifampicin resistance-conferring mutation prompting treatment as potential MDR cases., Methods: Further laboratory investigations on the cultured isolates included GenoType MTBDR plus assay, phenotypic drug susceptibility tests using the BD BACTEC MGIT culture system and MIC broth microdilution tests. Sequencing of the rpoB gene was performed using Sanger sequencing and WGS., Results: Phenotypic drug susceptibility tests determined the isolates to be rifampicin susceptible. Molecular investigations identified an A451V (codon 532) mutation in the Mycobacterium tuberculosis rpoB gene that has not previously been found to cause rifampicin resistance. Genome sequencing revealed that the three isolates' genomes differed by ≤5 SNPs, indicating a high likelihood of recent transmission events. Furthermore, a cluster of six related M. tuberculosis isolates from our in-house typing database showed four were highly related; all were rifampicin susceptible and lacked this mutation., Conclusions: False detection of rifampicin resistance, albeit rare, should be considered possible with Xpert ® MTB/RIF Ultra assay, particularly in low TB incidence settings. Confirmatory sequencing methods should be performed to prevent the unnecessary use of second-line anti-tuberculous drugs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Published
2021
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