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  1. Article ; Online: Therapeutic Failure and Acquired Bedaquiline and Delamanid Resistance in Treatment of Drug-Resistant TB.

    Millard, James / Rimmer, Stephanie / Nimmo, Camus / O'Donnell, Max

    Emerging infectious diseases

    2023  Volume 29, Issue 5, Page(s) 1081–1084

    Abstract: New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of ... ...

    Abstract New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of bedaquiline and delamanid resistance in a 55-year-old woman in South Africa with extensively drug-resistant tuberculosis and known HIV.
    MeSH term(s) Female ; Humans ; Middle Aged ; Diarylquinolines/pharmacology ; Diarylquinolines/therapeutic use ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/complications ; Nitroimidazoles/pharmacology ; Nitroimidazoles/therapeutic use ; Oxazoles/pharmacology ; Oxazoles/therapeutic use
    Chemical Substances bedaquiline (78846I289Y) ; Diarylquinolines ; OPC-67683 ; Antitubercular Agents ; Nitroimidazoles ; Oxazoles
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1380686-5
    ISSN 1080-6059 ; 1080-6040
    ISSN (online) 1080-6059
    ISSN 1080-6040
    DOI 10.3201/eid2905.221716
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Therapeutic Failure and Acquired Bedaquiline and Delamanid Resistance in Treatment of Drug-Resistant TB

    James Millard / Stephanie Rimmer / Camus Nimmo / Max O’Donnell

    Emerging Infectious Diseases, Vol 29, Iss 5, Pp 1081-

    2023  Volume 1084

    Abstract: New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of ... ...

    Abstract New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of bedaquiline and delamanid resistance in a 55-year-old woman in South Africa with extensively drug-resistant tuberculosis and known HIV.
    Keywords tuberculosis and other mycobacteria ; bacteria ; antimicrobial resistance ; bedaquiline ; delamanid ; XDR TB ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Treatment of Highly Drug-Resistant Pulmonary Tuberculosis.

    Nimmo, Camus / Naidoo, Kogieleum / O'Donnell, Max

    The New England journal of medicine

    2020  Volume 382, Issue 24, Page(s) 2376

    MeSH term(s) Extensively Drug-Resistant Tuberculosis ; Humans ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary
    Language English
    Publishing date 2020-06-03
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2009939
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Reducing turnaround time for inpatient plain film imaging.

    Nimmo, Camus / Groombridge, Heather / Wendruff, Andrew

    Future hospital journal

    2019  Volume 3, Issue Suppl 2, Page(s) s27

    Language English
    Publishing date 2019-05-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2775176-4
    ISSN 2055-3331 ; 2055-3323
    ISSN (online) 2055-3331
    ISSN 2055-3323
    DOI 10.7861/futurehosp.3-2s-s27
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  5. Article ; Online: Evolution of <i>Mycobacterium tuberculosis</i> drug resistance in the genomic era.

    Nimmo, Camus / Millard, James / Faulkner, Valwynne / Monteserin, Johana / Pugh, Hannah / Johnson, Eachan Oliver

    Frontiers in cellular and infection microbiology

    2022  Volume 12, Page(s) 954074

    Abstract: ... Mycobacterium tuberculosis ... has acquired drug resistance to all drugs that have been used against it, including those only recently introduced into clinical practice. Compared to other bacteria, it has a well conserved genome due to its role as an ... ...

    Abstract Mycobacterium tuberculosis has acquired drug resistance to all drugs that have been used against it, including those only recently introduced into clinical practice. Compared to other bacteria, it has a well conserved genome due to its role as an obligate human pathogen that has adapted to a niche over five to ten thousand years. These features facilitate reconstruction and dating of M. tuberculosis phylogenies, giving key insights into how resistance has been acquired and spread globally. Resistance to each new drug has occurred within five to ten years of clinical use and has occurred even more rapidly with recently introduced drugs. In most cases, resistance-conferring mutations come with a fitness cost, but this can be overcome by compensatory mutations which restore fitness to that of wild-type bacteria. It is likely that M. tuberculosis acquires drug resistance while maintaining limited genomic variability due the generation of low frequency within-host variation, combined with ongoing purifying selection causing loss of variants without a clear fitness advantage. However, variants that do confer an advantage, such as drug resistance, can increase in prevalence amongst all bacteria within a host and become the dominant clone. These resistant strains can then be transmitted leading to primary drug resistant infection in a new host. As many countries move towards genomic methods for diagnosis of M. tuberculosis infection and drug resistance, it is important to be aware of the implications for the evolution of resistance. Currently, understanding of resistance-conferring mutations is incomplete, and some targeted genetic diagnostics create their own selective pressures. We discuss an example where a rifampicin resistance-conferring mutation which was not routinely covered by standard testing became dominant. Finally, resistance to new drugs such as bedaquiline and delamanid is caused by individually rare mutations occurring across a large mutational genomic target that have been detected over a short time, and do not provide statistical power for genotype-phenotype correlation - in contrast to longer-established drugs that form the backbone of drug-sensitive antituberculosis therapy. Therefore, we need a different approach to identify resistance-conferring mutations of new drugs before their resistance becomes widespread, abrogating their usefulness.
    MeSH term(s) Humans ; Mycobacterium tuberculosis/genetics ; Rifampin ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Genomics ; Tuberculosis, Lymph Node ; Mutation ; Drug Resistance ; Drug Resistance, Multiple, Bacterial ; Microbial Sensitivity Tests
    Chemical Substances Rifampin (VJT6J7R4TR) ; Antitubercular Agents
    Language English
    Publishing date 2022-10-07
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2022.954074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Opportunities and limitations of genomics for diagnosing bedaquiline-resistant tuberculosis: a systematic review and individual isolate meta-analysis.

    Nimmo, Camus / Bionghi, Neda / Cummings, Matthew J / Perumal, Rubeshan / Hopson, Madeleine / Al Jubaer, Shamim / Naidoo, Kogieleum / Wolf, Allison / Mathema, Barun / Larsen, Michelle H / O'Donnell, Max

    The Lancet. Microbe

    2024  Volume 5, Issue 2, Page(s) e164–e172

    Abstract: Background: Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic ... ...

    Abstract Background: Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
    Methods: We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
    Findings: 18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
    Interpretation: Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
    Funding: Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
    MeSH term(s) United States ; Humans ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Diarylquinolines/pharmacology ; Diarylquinolines/therapeutic use ; Tuberculosis/drug therapy ; Mycobacterium tuberculosis/genetics ; Genomics
    Chemical Substances bedaquiline (78846I289Y) ; Antitubercular Agents ; Diarylquinolines
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Systematic Review ; Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2666-5247
    ISSN (online) 2666-5247
    DOI 10.1016/S2666-5247(23)00317-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Baseline and treatment-emergent bedaquiline resistance in drug-resistant tuberculosis: a systematic review and meta-analysis.

    Perumal, Rubeshan / Bionghi, Neda / Nimmo, Camus / Letsoalo, Marothi / Cummings, Matthew J / Hopson, Madeleine / Wolf, Allison / Jubaer, Shamim Al / Padayatchi, Nesri / Naidoo, Kogieleum / Larsen, Michelle H / O'Donnell, Max

    The European respiratory journal

    2023  Volume 62, Issue 6

    MeSH term(s) Humans ; Diarylquinolines/therapeutic use ; Tuberculosis, Multidrug-Resistant/drug therapy ; Antitubercular Agents/therapeutic use ; Mycobacterium tuberculosis
    Chemical Substances bedaquiline (78846I289Y) ; Diarylquinolines ; Antitubercular Agents
    Language English
    Publishing date 2023-12-14
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Letter
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.00639-2023
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    Zs.A 2322: Show issues Location:
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  8. Article ; Online: Time to put out the lights on sleeping sickness?

    Nimmo, Camus

    Travel medicine and infectious disease

    2010  Volume 8, Issue 4, Page(s) 263–268

    Abstract: Sleeping sickness (or Human African Trypanosomiasis, HAT) is a potentially fatal parasitic disease that affects a large proportion of sub-Saharan Africa. It was epidemic in the early 20th century before being nearly eradicated through a variety of ... ...

    Abstract Sleeping sickness (or Human African Trypanosomiasis, HAT) is a potentially fatal parasitic disease that affects a large proportion of sub-Saharan Africa. It was epidemic in the early 20th century before being nearly eradicated through a variety of control programmes. Despite this, there was a resurgence in the 1980s and 90s following relaxation of these programmes. Recent advances are reversing this trend once more. However, more research is required to improve diagnosis and treatment, and to better understand the epidemiology of HAT if complete eradication is to be achieved in the future.
    MeSH term(s) Africa/epidemiology ; Animals ; Disease Reservoirs ; Disease Vectors ; Female ; Humans ; Male ; Trypanosomiasis, African/diagnosis ; Trypanosomiasis, African/epidemiology ; Trypanosomiasis, African/prevention & control
    Language English
    Publishing date 2010-07
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2170891-5
    ISSN 1873-0442 ; 1477-8939
    ISSN (online) 1873-0442
    ISSN 1477-8939
    DOI 10.1016/j.tmaid.2010.05.001
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  9. Article ; Online: Implementing rapid diagnostics for COVID-19.

    Nimmo, Camus / Agbetile, Joshua / Bhowmik, Angshu / Capocci, Santino / Rajakulasingam, Raj K

    The Lancet. Respiratory medicine

    2020  Volume 9, Issue 1, Page(s) e7

    MeSH term(s) COVID-19 ; Hospitals ; Humans ; Point-of-Care Testing ; Prospective Studies ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-11-12
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(20)30526-9
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  10. Article: Opportunities and limitations of genomics for diagnosing bedaquiline-resistant tuberculosis: an individual isolate metaanalysis.

    Nimmo, Camus / Bionghi, Neda / Cummings, Matthew J / Perumal, Rubeshan / Hopson, Madeleine / Al Jubaer, Shamim / Wolf, Allison / Mathema, Barun / Larsen, Michelle H / O'Donnell, Max

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: Clinical bedaquiline resistance predominantly involves mutations in : Methods: We screened public databases for articles published until October 2022. Eligible studies performed sequencing of at least : Results: Eighteen eligible ... ...

    Abstract Background: Clinical bedaquiline resistance predominantly involves mutations in
    Methods: We screened public databases for articles published until October 2022. Eligible studies performed sequencing of at least
    Results: Eighteen eligible studies were identified, comprising 975
    Discussion: Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified a limited number of mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics.
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.04.23289023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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