Sterile tuberculous granuloma in a patient with XDR-TB treated with bedaquiline, pretomanid and linezolid

2021 ◽  
Vol 14 (12) ◽  
pp. e245612
Author(s):  
Pauline Howell ◽  
Caryn Upton ◽  
Nokuphiwa Mvuna ◽  
Morounfolu Olugbosi
Keyword(s):  
Excisional Biopsy ◽  
Multidrug Resistant ◽  
Trial Participant ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
First Case ◽  
Mdr Tb ◽  
Tuberculous Granuloma ◽  
Cns Penetration ◽  
Global Eradication

Drug-resistant tuberculosis (DR-TB) continues to pose a threat to the global eradication of TB. Regimens for extensively drug-resistant (XDR) TB are lengthy and poorly tolerated, often with unsuccessful outcomes. The TB Alliance Nix-TB trial investigated the safety and efficacy of a 26-week regimen of bedaquiline, pretomanid and linezolid (BPaL) in participants with XDR-TB, multidrug-resistant (MDR) TB treatment failure or intolerance. In this trial 9 out of 10 participants were cured. We describe a trial participant with XDR-TB who presented with new-onset seizures soon after BPaL treatment completion. Imaging showed a right temporal ring-enhancing lesion, and a sterile tuberculous granuloma was confirmed after a diagnostic, excisional biopsy. Learning points include management of a participant with a tuberculoma after BPaL completion, efficacy of new medications for central nervous system (CNS) TB and a review of their CNS penetration. This is the first case of pretomanid use in CNS TB.

Global Threats and the Control of Multidrug-Resistant Tuberculosis

2011 ◽  
Vol 6 (4) ◽  
pp. 443-450 ◽  
Author(s):  
Kazuo Kobayashi ◽  
◽  
Manabu Ato ◽  
Sohkichi Matsumoto ◽  
Keyword(s):  
Immune Deficiency Syndrome ◽  
Multidrug Resistant ◽  
Deficiency Syndrome ◽  
Chemotherapeutic Agents ◽  
Drug Resistant ◽  
Injectable Drugs ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Causes Of Mortality ◽  
Active Disease

About one-third of the world’s population has been infected with Mycobacterium tuberculosis. Active disease develops in about 9 million people per year, and tuberculosis is responsible for 2 million deaths per year. The disease caused by this bacterium, tuberculosis (TB), remains one of the leading causes of mortality caused by infection worldwide and is a major threat to global health. The situation of TB is recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with human immunodeficiency virus/acquired immune deficiency syndrome, which greatly increases the risk of latent M. tuberculosis infection progressing to active disease. Multidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of M. tuberculosis that are at least resistant to isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by MDR strains that are also resistant to any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin). MDR- and XDR-TB are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade. In this review, we focus on threats of MDR-TB and the research and development of improved diagnostics, new chemotherapeutic agents, and vaccine candidates for MDR-TB.

scholarly journals Multidrug-Resistant Tuberculosis in Alberta and British Columbia, 1989 to 1998

1999 ◽  
Vol 6 (2) ◽  
pp. 155-160 ◽  
Author(s):  
Ahmed Hersi ◽  
Kevin Elwood ◽  
Robert Cowie ◽  
Dennis Kunimoto ◽  
Richard Long
Keyword(s):  
British Columbia ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Foreign Born ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Culture Positive

OBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (P<0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.

scholarly journals Genotypic diversity of multi- and pre-extremely drug-resistant Mycobacterium tuberculosis isolates from Morocco

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253826
Author(s):  
Amal Oudghiri ◽  
Ghizlane Momen ◽  
Achraf Aainouss ◽  
Amin Laglaoui ◽  
My Driss El Messaoudi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Genotypic Diversity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Control Programs ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Database Clustering ◽  
High Level

In Morocco, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase especially within previously treated cases; these MDR cases may evolve to extensively drug resistant tuberculosis (XDR-TB) raising major concern to TB control programs. From an epidemiological window, scarce informations are available about the genetic diversity of Mycobacterium tuberculosis (MTB) strains fueling these forms of resistance. The aim of this study was to assess to genetic diversity of MDR-MTB strains. Hence, this prospective study was conducted on patients diagnosed with MDR-TB at Pasteur Institute of Casablanca from 2010 to 2013. A total of 70 MDR-MTB isolates were genotyped by spoligotyping and 15-loci MIRU-VNTR methods. Spoligotyping generated four orphan patterns, five unique profiles whereas 61 strains were grouped in nine clusters (2 to 25 strains per cluster), the clustering rates being 87.1%. Subtyping by 15 loci MIRU-VNTR splitted all clusters already established by spoligotyping and generated 70 unique profiles not recognized in SITVIT2 database; clustering rate was equal to zero. HGDI analysis of 15 loci MIRU demonstrated that eight out of 15 loci were highly discriminant. Of note, all pre-XDR strains belongs to many clades, meaning that there no association between gyrA mutants and particular clade. Overall, the data generated by this study (i) describe the population structure of MDR MTBC in Morocco which is highly homogenous, (ii) confirm that TB in Morocco is almost exclusively transmitted by modern and evolutionary lineages with high level of biodiversity seen by MIRU, and (iii) validate the use of optimized 15-loci MIRU-VNTR format for future investigations in Morocco.

scholarly journals Epidemiology of drug-resistant tuberculosis in Chongqing, China: a retrospective observational study from 2010 to 2017

2019 ◽  
Author(s):  
Bo Wu ◽  
Ya Yu ◽  
Changting Du ◽  
Ying Liu ◽  
Daiyu Hu
Keyword(s):  
Observational Study ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Policy Support ◽  
Retrospective Observational Study ◽  
Drug Resistant ◽  
Notification Rate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractChina is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.09 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases among all notified TB cases. The treatment success rate of MDR/RR-TB was 50.66% in this period. The rate of MDR/RR-TB in new TB cases was 6.23%, and this rate in previously treated TB cases was 32.7%. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

scholarly journals Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 498
Author(s):  
Priya Rathi ◽  
Kalpita Shringarpure ◽  
Bhaskaran Unnikrishnan ◽  
Abhinav Pandey ◽  
Abhirami Nair
Keyword(s):  
Multidrug Resistant ◽  
Diagnosis And Treatment ◽  
Patient Treatment ◽  
Drug Resistant ◽  
Treatment Pathways ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however the diagnostic rate was high in public HCF. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

scholarly journals Draft Genome Sequences of Two Drug-Resistant Mycobacterium tuberculosis Isolates from Myanmar

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Htin Lin Aung ◽  
Thanda Tun ◽  
Elizabeth Permina ◽  
Wint Wint Nyunt ◽  
Si Thu Aung ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Health Concerns ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) and lately, extensively drug-resistant TB (XDR-TB) are increasing global health concerns. Here, we present the genome sequences of two MDR-TB isolates from Myanmar, one of 27 countries with a high MDR-TB burden, and describe a number of mutations consistent with these being XDR-TB isolates.

scholarly journals Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e031663
Author(s):  
Nomonde Ritta Mvelase ◽  
Yusentha Balakrishna ◽  
Keeren Lutchminarain ◽  
Koleka Mlisana
Keyword(s):  
South Africa ◽  
Diagnostic Algorithm ◽  
Multidrug Resistant ◽  
Continuous Phase ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
Mdr Tb

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the highest burdened province of South Africa during a period where major changes in diagnostic algorithm were implemented.SettingThis study was conducted at the central academic laboratory of the KwaZulu-Natal province of South Africa.ParticipantsWe analysed data for all MTB cultures performed in the KwaZulu-Natal province between 2011 and 2014. The data were collected from the laboratory information system.ResultsOut of 88 559 drug susceptibility results analysed, 18 352 (20.7%) were resistant to rifampicin (RIF) and 19 190 (21.7%) showed resistance to isoniazid (INH). The proportion of rifampicin resistant cases that were mono-resistant increased from 15.3% in 2011 to 21.4% in 2014 while INH mono-resistance (IMR) showed a range between 13.8% and 21.1%. The multidrug-resistant tuberculosis (MDR-TB) rates increased from 18.8% to 23.9% and the proportion of MDR-TB cases that had extensively drug-resistant tuberculosis remained between 10.2% and 11.1%. Most drug resistance was found in females between the ages of 15 and 44 years and the northern districts bordering high MDR-TB regions had the highest MDR-TB rates.ConclusionOur findings show increasing RIF mono-resistance (RMR) and a substantial amount of IMR. This highlights a need for an initial test that detects resistance to both these drugs so as to avoid using RIF monotherapy during continuous phase of treatment in patients with IMR. Furthermore, addition of INH will benefit patients with RMR. Although DR-TB is widespread, HIV and migration influence its distribution; therefore, TB control strategies should include interventions that target these aspects.

scholarly journals Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

2019 ◽  
Vol 28 (152) ◽  
pp. 190035 ◽  
Author(s):  
Emanuele Pontali ◽  
Mario C. Raviglione ◽  
Giovanni Battista Migliori
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Optimal Outcomes ◽  
Resistant Tuberculosis ◽  
Prolonged Duration ◽  
Mdr Tb ◽  
Revised Definitions ◽  
Health Organization

Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20–24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9–10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.

Safety and Efficacy of Delamanid in the Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

2013 ◽  
Vol 5 ◽  
pp. CMT.S11675 ◽  
Author(s):  
Stephen K. Field
Keyword(s):  
Multidrug Resistant ◽  
Phase Iii ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improved Outcomes ◽  
Resistance Patterns ◽  
Mdr Tb ◽  
Phase Iii Study

Globally, the incidence of tuberculosis (TB) is declining but the proportion of drug-resistant cases has increased. Strains resistant to both isoniazid and rifampin, and possibly other antibiotics, called multidrug-resistant (MDR), are particularly difficult to treat. Poorer outcomes, including increased mortality, occur in patients infected with MDR strains and the costs associated with treatment of MDR-TB are substantially greater. The recent recognition of MDR-TB and strains with more complex resistance patterns has stimulated the development of new TB medications including fluoroquinolones, oxazolidinones, diarylquinolines, nitroimidazopyrans, ethylenediamines, and benzothiazinones. Bedaquiline, a diarylquinoline, was approved for the treatment of MDR-TB in 2012. Addition of delamanid to WHO-approved treatment improved outcomes for MDR-TB and for extensively drug-resistant TB in a large randomized, controlled phase II clinical trial and is undergoing evaluation in a large international phase III study. This review will focus on MDR-TB and the role of delamanid in its treatment.

scholarly journals Primary Clofazimine and Bedaquiline Resistance among Isolates from Patients with Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Jian Xu ◽  
Bin Wang ◽  
Minghao Hu ◽  
Fengmin Huo ◽  
Shaochen Guo ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated ◽  
Alamarblue Assay

ABSTRACT Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine of Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimine-resistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were ≥1.2 μg/ml. Four isolates with cross-resistance to bedaquiline had Rv0678 mutations. The other isolate with no resistance to bedaquiline had an Rv1979c mutation. This study adds to a recent study showing that 6.3% of MDR-TB patients without prior clofazimine or bedaquiline exposure harbored isolates with Rv0678 mutations, which raises concern that preexisting resistance to these drugs may be associated with prior TB treatment. Furthermore, we propose a tentative breakpoint of 1.2 μg/ml for clofazimine resistance using the MABA method. More-widespread surveillance and individualized testing for clofazimine and bedaquiline resistance, together with assessment of their clinical usage, especially among previously treated and MDR-TB patients, are warranted.

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