Tuberculosis (TB): Practice Essentials, Background, Pathophysiology
Two Studies Evaluate Non-Tuberculous Mycobacterium Causes And ...
Non-tuberculous mycobacterium (NTM), a serious lung disease, can be identified in different ways in patients. Recently, 2 studies evaluated specific identification and causes of NTM in order to help predict treatment outcomes in the future.
Non-tuberculous mycobacterium (NTM), a serious lung disease, can be identified in different ways in patients. Recently, 2 studies evaluated specific identification and causes of NTM in order to help predict treatment outcomes in the future.
Currently, NTM is frequently not identified using 16S rRNA sequencing, even for samples with positive cultures for these organisms. Since NTM typically has only 1 or 2 copies per genome, they may be underrepresented—therefore, the standard 16S sequencing may not be the best identification method.
One study, recently presented at The American Thoracic Society 2018 International Conference, investigated the airway microbiota in patients with bronchiectasis using a different sequencing method—one that was biased towards mycobacterium to help identify low abundance organisms.1
The study included 20 subjects with lower airway sampling and the 16S rRNA gene sequence was used to analyze the microbiome composition. Also, a nested mycobacteriome polymerase chain reaction (PCR) approach was used to analyze the bronchoalveolar lavage (BAL) samples. Then, this approach was validated with a larger cohort with samples collected from patients with bronchiectasis, according to the study.
The BAL samples detected mycobacterium in 4 samples with standard 16S rRNA gene sequencing approaches. The nested mycobacterium approach was able to detect mycobacterium in the same 4 samples, as well as 3 other culture positive samples with sequences that match mycobacterium avium. Additionally, 1 NTM culture negative sample with mycobacterium was identified.
"The low abundance of Mycobacterium in NTM+ samples supports prior data showing that a 16S approach may under-represent this genus," concluded the study. "Addition of Mycobacterium specific primers help further describe the microbiome in this disease."
The other study focused on evaluation of the clinical characteristics and treatment outcomes in patients with NTM lung disease (NTM-LD) caused by mixed infection with two major NTM pathogens—mycobacterium avium complex (MAC) and M. Abscessus complex (MABC).2
The study included 71 consecutive patients who were diagnosed with NTM-LD caused by mixed infection with MAC and MABC between 2010 and 2015. The treatment outcome was evaluated at 12 months after antibiotic treatment and sputum conversion was defined as 3 consecutive negative cultures of all NTM organisms.
The results demonstrated that mixed infection with MAC and M. Massiliense was more common (66%) than MAC and M. Abscessus (34%). Additionally, M. Avium was frequently associated with M. Massiliense, while M. Intracellulare was associated with M. Abscessus. Sputum culture conversion rates were found to be lower in patients infected with MAC and M. Abscessus than those with MAC and M. Massiliense.
"Mixed infection with MAC and MABC typically developed in patients with nodular bronchiectatic form of NTM-LD," the study concluded. "Precise identification of etiologic NTM organisms could help predict treatment outcomes in these patients."
References
1. Sulaiman I, Wu B, Scaglione BD, et al. The mycobacteriome: A nested approach to identify non-tuberculous mycobacterium. Presented at the American Thoracic Society 2018 International Conference; San Diego, California; May 18-23, 2018; Abstract 9969.
2. Shin S, Jhun B, Choe J, et al. Nontuberculous mycobacterial lung diseases caused by mixed infection with mycobacterium avium complex and mycobacterium abscessus complex. Presented at the American Thoracic Society 2018 International Conference; San Diego, California; May 18-23, 2018; Abstract 2602.
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BioVersys Joins EU-Funded RespiriNTM Programme To Accelerate ...
BASEL, Switzerland, Oct. 22, 2024 (GLOBE NEWSWIRE) --
BioVersys AG, a multi-asset, clinical stage biopharmaceutical company focusing on research and development of novel antibacterial products for serious life-threatening infections caused by multi-drug resistant ("MDR") bacteria, announced today that it has joined the EU-funded RespiriNTM programme, an 8-year journey exploring multiple approaches to determine new targets for anti-mycobacterial compounds, define and optimize novel inhibitors and move these through the process of hit-to-lead up until the First-in-Human trials. BioVersys' in-house non-tubercular mycobacteria (NTM) project will have access to up to approximately €2 million in non-dilutive funding from the original IMI2 RespiriNTM grant of approximately €5.7 million, and to key capabilities of established consortium partners to develop novel candidates to address NTM pulmonary disease (NTM-PD).
NTM-PD is estimated to affect more than 86,000 people in the US according to the American Lung Association and antimicrobial resistance (AMR) is a major global health threat with currently available therapeutics becoming more and more obsolete due to AMR.1 This is of greatest concern when addressing NTM-PD, as chronic antibiotic treatments of 12-24 months required for these infections often lead to the development of antibiotic resistance. Due to the lack of effective treatment options, current cure rates for NTM-PD are as low as 30-50%.2 Particularly vulnerable to NTM-PD are people who suffer from structural airway diseases such as cystic fibrosis, COPD and bronchiectasis.
BioVersys' NTM program is derived from the company's proprietary Ansamycin Chemistry platform. The BioVersys' research team is developing a novel and highly potent broad-spectrum anti-NTM ansamycin, suitable for oral or inhalation therapy that is devoid of cross-resistance with other therapeutic classes. Since NTM-PD patients are often on multi-drug regimens, the company focuses on developing molecules that do not show any significant potential for drug-drug interactions.
Meindert H. Lamers, Associate Professor, Leiden University Medical Center & RespiriNTM Project Coordinator: "Working together with BioVersys on the RespiriNTM project is a unique opportunity. Their powerful ansamycin class of inhibitors have the potential to provide an effective and highly needed treatment option for NTM infections, which fits perfectly with the aims of the RespiriNTM project. BioVersys' strong drive to deliver a novel NTM antibiotic has invigorated the RespiriNTM project. Our collaboration to date has been very stimulating and I am very much looking forward to deepening our collaboration with BioVersys over the coming years."
Dr. Sergio Lociuro, Chief Scientific Officer of BioVersys: "Following on from the recent successes of TRIC-TB, we are very pleased to have the opportunity to join a second IMI2 JU funded programme, which is tackling another area of high unmet medical need. RespiriNTM is a strong consortium of many expert partners with valuable experience in the field of antimicrobial resistance. We aim to develop our broad-spectrum NTM candidates into effective treatments against these difficult to treat pulmonary diseases to positively impact patients' lives."
About RespiriNTMMycobacterium avium complex (MAC) and Mycobacterium abscessus subspecies (MAB) cause several hundreds of thousands of infections worldwide each year. Unlike the well know related species M. Tuberculosis, there are currently limited and poor treatment options to address these pathogens with significant levels of relapse and unacceptably high mortality rates, approaching 45%.3 Therefore, there is an urgent need for antibiotics that can treat the debilitating diseases that are caused by the Non-Tuberculous Mycobacteria (NTM), M. Avium complex and M. Abscessus. The RespiriNTM project aims to develop novel antibiotics that target the RNA transcription machinery that is required for protein production in the cell. Through this work we aim to develop desperately needed antibiotics that work against M. Avium and M. Abscessus that form an increasing threat to global health. RespiriNTM is part of the IMI AMR Accelerator Programme.
About non-tubercular mycobacteriaNon-tuberculous Mycobacteria (NTM) are ubiquitous environmental bacteria whose common clinical manifestation is pulmonary disease (NTM-PD) caused most frequently by Mycobacterium avium complex (MAC) and Mycobacterium abscessus subspecies (MAB).4 NTM-PD affects approximately 250,000 people per year, predominantly in North America and Asia.4 Treatment of NTM infections is challenging due to variable intrinsic bacterial susceptibility, acquired resistance to commonly used antimicrobial agents, length of therapy (at least 12 months) and adverse effects associated with current treatment options. Macrolide-based, triple drug regimens, plus aminoglycosides for chronic/relapsing infections5 are considered only moderately effective for treating MAC, whereas no therapy of predictable efficacy exists for the treatment of M. Abscessus, a pathogen associated with up to 50% mortality.6 People with predisposed conditions, including cystic fibrosis (CF), other lung diseases and immune-compromised patients are more easily colonised. Alarmingly, the incidence of NTM infections among people living with CF has increased from 3.3% to 22.6%, with MAB becoming a very prominent pathogen.7
Statements or views expressed in this release are of those of the respective organizations or persons and the IMI2 JU is not responsible for any use of the information contained herein.
The RespiriNTM project has received funding from the Innovative Health Initiative 2 Joint Undertaking (JU) under grant agreement No 853932. This Joined Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.
About the Innovative Medicines InitiativeThe Innovative Medicines Initiative (IMI) IMI is a partnership between the European Union and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA). It was set up to improve health by speeding up the development of, and patient access to, the next generation of medicines, particularly in areas where there is an unmet medical or social need. It works by facilitating collaboration between the key players involved in healthcare research, including universities, pharmaceutical companies, other companies active in healthcare research, small and medium-sized enterprises (SMEs), patient organisations, and medicines regulators. This approach has proven highly successful, and IMI projects are delivering exciting results that are helping to advance the development of urgently-needed new treatments in diverse areas. IMI projects are now managed by the Innovative Health Initiative (IHI), which builds on the successes of IMI and is a cross-sectoral public-private partnership involving a wider range of health industries.
About BioVersysBioVersys AG is a multi-asset, clinical stage biopharmaceutical company focused on identifying, developing and commercializing novel antibacterial products for serious life-threatening infections caused by multi-drug resistant ("MDR") bacteria. Derived from the company's two internal technology platforms (TRIC and Ansamycin Chemistry), candidates are designed and developed to overcome resistance mechanisms, block virulence production and directly affect the pathogenesis of harmful bacteria towards the identification of new treatment options in the antimicrobial and microbiome fields. This enables BioVersys to address the high unmet medical need for new treatments against life-threatening resistant bacterial infections and bacteria-exacerbated chronic inflammatory microbiome disorders. The company's most advanced research and development programs address nosocomial infections of Acinetobacter baumannii (BV100, Phase 2), and tuberculosis (alpibectir, Phase 2a, in collaboration with GlaxoSmithKline (GSK) and a consortium of the University of Lille, France). BioVersys is located in the biotech hub of Basel, Switzerland.
BioVersys contactSylvia Mundt, Tel. +41 61 633 22 50; Mail: IR@bioversys.Comwww.Bioversys.Com
https://twitter.Com/Bioversyshttps://www.Linkedin.Com/company/bioversys-ag
1 Lancet, Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis, VOLUME 399, ISSUE 10325, P629-655, FEBRUARY 12, 20222 Wang et al., 2022; Novosad et al., 2017; Lee et al., 2021; Mourad et al., 20213 The Impact of Nontuberculous Mycobacteria Species on Mortality in Patients with Nontuberculous Mycobacterial Lung Disease. Wang et al, 2022, Frontiers in Microbiology. Doi:10.3389/fmicb.2022.9092744 Hamed KA & G. Tillotson "A narrative review of nontuberculous mycobacterial pulmonary disease: microbiology, epidemiology, diagnosis, and management challenges" Ex. Rev. Resp. Med. (2023), 17 (11), 973 - 988 https://doi.Org/10.1080/17476348.2023.22831355 Daley CL et al. "Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline" Eur. Resp. J. (2020), 56, 2000535; https://doi.Org/10.1183/13993003.00535-2020; Griffith DE et al. "An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases" Am. J. Respir. Crit. Care Med. (2007), 175, 367–416; https://doi.Org/10.1164/rccm.200604-571ST6 Jhun BW et al. "Prognostic factors associated with long-term mortality in 1445 patients with nontuberculous mycobacterial pulmonary disease: a 15-year follow-up study" Eur. Resp. J. (2020), 55, 1900798; https://doi.Org/10.1183/13993003.00798-20197 Degiacomi G. Et al. "Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients" Int. J. Mol. Sci. (2019), 20, 5868; doi: 10.3390/ijms20235868
Arikayce Shows Promise Among Patients Newly Diagnosed With NTM ... - Healio
September 05, 2023
2 min read
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Key takeaways:A drug that treats nontuberculous mycobacterial lung infections caused by Mycobacterium avium complex performed well among newly diagnosed patients who had not started antibiotics, its manufacturer said.
In 2018, Arikayce became the first treatment approved under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs, which streamlines the development of drugs meant to treat serious but rare infections. It was approved for patients who cannot be treated with conventional M. Avium therapies.
Arikayce resulted in an improved quality of life for people with newly diagnosed or recurrent nontuberculous mycobacterial lung infections. Image: Adobe StockInsmed, the company that makes Arikayce (amikacin liposome inhalation suspension), said in a press release that it plans to work with regulators to accelerate the approval of Arikayce for newly infected patients.
The company said the ongoing phase 3b ENCORE trial will continue to enroll participants into 2024, and that topline data from the trial are expected in 2025.
According to results announced Tuesday by Insmed, Arikayce resulted in an improved quality of life for people with newly diagnosed or recurrent nontuberculous mycobacterial (NTM) lung infections caused by M. Avium complex based on patient-reported outcomes.
NTM are common in the environment and can form biofilms that survive in water systems in residential, office and health care facilities, and are resist to chlorination, according to the CDC.
People with underlying lung disease or who are immunosuppressed are most at risk for NTM infection, although it is typically not transmitted from person to person.
Just under 90,000 people in the United States have NTM, according to the American Lung Association, with treatment generally requiring several antibiotics for multiple years. Experts have said lifestyle changes such as exercise and diet improvements can help alleviate symptoms.
"The ARISE study represents a clear and unambiguous win for the entire NTM community," Insmed Chief Medical Officer Martina Flammer, MD, MBA, said in the press release. "We are thrilled that these results validate a [patient-reported outcome] tool in NTM lung disease, but also show that patients treated with an Arikayce-based regimen felt better versus patients in the comparator arm."
The phase 3 ARISE trial enrolled 99 people who were randomly assigned in a 1:1 ratio to receive either Arikayce plus macrolide-based background regimen or placebo plus macrolide-based background regimen for 6 months, followed by 1 month off treatment.
Among patients in the treatment group, as measured by a Quality of Life instrument, 43.8% of people achieved an improvement in quality of life compared with 33.3% of people in the placebo group, according to Insmed.
The company said a strong trend toward improvement was seen from baseline at month 7, and people in the treatment group achieved higher culture conversion rates at month 7 compared with patients in the placebo group (78.8% vs. 47.1%), although the trial was not powered to show a statistically significant difference between treatment arms.
"We look forward to discussing these excellent results from this well-executed study in the near future with regulators," Insmed's Chief Development Officer Kevin Mange, MD, MSCE, said in the release.
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