POPULARITY
3 episodes with multidrug
4 episodes with multidrug
2 episodes with multidrug
2 episodes with multidrug
2 episodes with multidrug
4 episodes with multidrug
4 episodes with multidrug
4 episodes with multidrug
3 episodes with multidrug
This week's episode we will discuss the resurgence of TB/ Tuberculosis. TB is a treatable and curable disease. Active, drug-susceptible TB disease is treated with a standard 6-month course of 4 antimicrobial drugs that are provided with information and support to the patient by a health worker or trained volunteer. Without such support, treatment adherence is more difficult. Since 2000, an estimated 66 million lives were saved through TB diagnosis and treatment. (credits: WHO) A total of 1.5 million people died from TB in 2020 (including 214 000 people with HIV). Worldwide, TB is the 13th leading cause of death and the second leading infectious killer after COVID-19 (above HIV/AIDS). In 2020, an estimated 10 million people fell ill with tuberculosis (TB) worldwide. 5.6 million men, 3.3 million women and 1.1 million children. TB is present in all countries and age groups. But TB is curable and preventable. In 2020, 1.1 million children fell ill with TB globally. Child and adolescent TB is often overlooked by health providers and can be difficult to diagnose and treat. In 2020, the 30 high TB burden countries accounted for 86% of new TB cases. Eight countries account for two thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. Only about one in three people with drug resistant TB accessed treatment in 2020. Globally, TB incidence is falling at about 2% per year and between 2015 and 2020 the cumulative reduction was 11%. This was over half way to the End TB Strategy milestone of 20% reduction between 2015 and 2020. An estimated 66 million lives were saved through TB diagnosis and treatment between 2000 and 2020. Globally, close to one in two TB-affected households face costs higher than 20% of their household income, according to latest national TB patient cost survey data. The world did not reach the milestone of 0% TB patients and their households facing catastrophic costs as a result of TB disease by 2020. By 2022, US$ 13 billion is needed annually for TB prevention, diagnosis, treatment and care to achieve the global target agreed at the UN high level-meeting on TB in 2018. Funding in low- and middle-income countries (LMICs) that account for 98% of reported TB cases falls far short of what is needed. Spending in 2020 amounted to US$ 5.3 billion less than half (41%) of the global target. There was an 8.7% decline in spending between 2019 and 2020 (from US$ 5.8 billion to US$ 5.3 billion), with TB funding in 2020 back to the level of 2016. Ending the TB epidemic by 2030 is among the health targets of the United Nations Sustainable Development Goals (SDGs). Tuberculosis (TB) is caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs. Tuberculosis is curable and preventable. TB is spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected. About one-quarter of the world's population has a TB infection, which means people have been infected by TB bacteria but are not (yet) ill with the disease and cannot transmit it. People infected with TB bacteria have a 5–10% lifetime risk of falling ill with TB. Those with compromised immune systems, such as people living with HIV, malnutrition or diabetes, or people who use tobacco, have a higher risk of falling ill. When a person develops active TB disease, the symptoms (such as cough, fever, night sweats, or weight loss) may be mild for many months. This can lead to delays in seeking care, and results in transmission of the bacteria to others. People with active TB can infect 5–15 other people through close contact over the course of a year. Without proper treatment, 45% of HIV-negative people with TB on average and nearly all HIV-positive people with TB will die. Who is most at risk? Tuberculosis mostly affects adults in their most productive years. However, all age groups are at risk. Over 95% of cases and deaths are in developing countries. People who are infected with HIV are 18 times more likely to develop active TB (see TB and HIV section below). The risk of active TB is also greater in persons suffering from other conditions that impair the immune system. People with undernutrition are 3 times more at risk. Globally in 2020, there were 1.9 million new TB cases that were attributable to undernutrition. Alcohol use disorder and tobacco smoking increase the risk of TB disease by a factor of 3.3 and 1.6, respectively. In 2020, 0.74 million new TB cases worldwide were attributable to alcohol use disorder and 0.73 million were attributable to smoking. Global impact of TB TB occurs in every part of the world. In 2020, the largest number of new TB cases occurred in the WHO South-East Asian Region, with 43% of new cases, followed by the WHO African Region, with 25% of new cases and the WHO Western Pacific with 18%. In 2020, 86% of new TB cases occurred in the 30 high TB burden countries. Eight countries accounted for two thirds of the new TB cases: India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. Symptoms and diagnosis Common symptoms of active lung TB are cough with sputum and blood at times, chest pains, weakness, weight loss, fever and night sweats. WHO recommends the use of rapid molecular diagnostic tests as the initial diagnostic test in all persons with signs and symptoms of TB as they have high diagnostic accuracy and will lead to major improvements in the early detection of TB and drug-resistant TB. Rapid tests recommended by WHO are the Xpert MTB/RIF Ultra and Truenat assays. Diagnosing multidrug-resistant and other resistant forms of TB (see Multidrug-resistant TB section below) as well as HIV-associated TB can be complex and expensive. Tuberculosis is particularly difficult to diagnose in children.
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Onyema Ogbuagu, MD, FACP, FIDSA - Multidrug-Resistant HIV: Evaluating HIV Treatment Strategies as Options Narrow
Multidrug-resistant organisms (MDROs) are a major concern for the nursing home population, who are at risk for developing severe infections. In today's webinar, we'll discuss an overview of MDROs in relation to long-term care.We're joined by Valerie Jividen, epidemiologist and lab-epi liaison for the West Virginia Department of Health Office of Epidemiology and Prevention Services. To contact Valerie Jividen, email Jividen, valerie.s.jividen@wv.gov.Watch RecordingDownload MDRO Outbreak ToolkitDownload Presentation SlidesCheck out our other interviews by visiting https://www.qualityinsights.org/ qin/multimedia This material was prepared by Quality Insights, a Quality Innovation Network - Quality Improvement Organization under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services (HHS). Views expressed in this material do not necessarily reflect the official views or policy of CMS or HHS, and any reference to a specific product or entity herein does not constitute endorsement of that product or entity by CMS or HHS. Publication number 12SOW-QI-GEN-070424-CC-A
Infections due to multidrug-resistant organisms (MDROs) are difficult to treat with increased morbidity, mortality, length of hospitalization, and health care costs. Author Susan S. Huang, MD, MPH, from the University of California Irvine School of Medicine, joins JAMA Deputy Editor Preeti Malani, MD, MSJ, to discuss a new study that used a regional intervention to prevent MDROs. Related Content: Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes
Today we speak with Dr Guglielmetti about the END-TB trial which looks at new all oral regimens for MDR-TB.REFERENCES1) https://endtb.org/2) Nyang'wa, Bern-Thomas, et al. "A 24-week, all-oral regimen for rifampin-resistant tuberculosis." New England Journal of Medicine 387.25 (2022): 2331-2343.3) Conradie, Francesca, et al. "Treatment of highly drug-resistant pulmonary tuberculosis." New England Journal of Medicine 382.10 (2020): 893-902.4) Diacon, Andreas H., et al. "Multidrug-resistant tuberculosis and culture conversion with bedaquiline." New England Journal of Medicine 371.8 (2014): 723-732.5) Gler, Maria Tarcela, et al. "Delamanid for multidrug-resistant pulmonary tuberculosis." New England Journal of Medicine 366.23 (2012): 2151-2160.6) Ahmad, Nafees, et al. "Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis." The Lancet 392.10150 (2018): 821-834.7) Lan, Zhiyi, et al. "Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis." The Lancet Respiratory Medicine 8.4 (2020): 383-394.APA |
Tuberculosis is one of the most deadly infectious diseases that still causes significant burden of disease, particularly in the developing world. The emergence of resistance to first line agents severely limits the therapeutic options and threaten the ability to control dissemination of this disease. Fortunately, new drugs and regimens are now emerging as important alternatives against these organisms. Today, we will discuss this topic with outstanding experts in the field. Welcome to the editors in conversation. Topics discussed: The burden of multidrug-resistant TB. New drugs and regimens for MDR TB. The current and future pipeline for TB Guests: Kelly Dooley, MD Ph.D. Professor and Addison B. Scoville, Jr., Chair in Medicine, Director, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center. Past Editor of AAC Sean Wasserman, MD Ph.D, Reader in Infectious Diseases at St Georges University of London and Associate Professor in the Division of Infectious Diseases and HIV Medicine at University of Cape Town, SA. Editor of AAC. This episode is brought to you by the Antimicrobial Agents and Chemotherapy journal available at aac.asm.org. If you plan to publish in AAC, ASM Members get up to 50% off publishing fees. Visit asm.org/membership to sign up. Visit journals.asm.org/journal/aac to browse issues and/or submit a manuscript. Subscribe to Editors in Conversation (free) on Apple Podcasts, Google Podcasts, Android, Spotify, Email.
Today we speak with Dr Chris Lowbridge about the amazing work of the TB teams in the Northern Territory. Chris talks about the challenges of controlling tuberculosis across 1.42 million square kilometres, more than 100 local languages, and some very isolated communities.ReferencesMeumann, Ella M., et al. "Tuberculosis in Australia's tropical north: a population-based genomic epidemiological study." The Lancet Regional Health–Western Pacific 15 (2021).Vigneswaran, Nilanthy, et al. "Factors leading to diagnostic delay in tuberculosis in the tropical north of Australia." Internal Medicine Journal (2023).Coorey, N. J., et al. "Risk factors for TB in Australia and their association with delayed treatment completion." The International Journal of Tuberculosis and Lung Disease 26.5 (2022): 399-405.Francis, J. R., et al. "Multidrug-resistant tuberculosis in Australia, 1998–2012." The international journal of tuberculosis and lung disease 22.3 (2018): 294-299.
The Desmond Tutu Tuberculosis (TB) Centre at Stellenbosch University found the first-ever safe and effective treatment to prevent multidrug-resistant TB in both children and adults. Researchers from the centre reported that an antibiotic taken for six months, once daily, could reduce the risk of developing drug-resistant TB in children by 56%. Associate Professor James Seddon, who was part of the team that discovered the treatment during a trial, said it took five years to get an outcomeSee omnystudio.com/listener for privacy information.
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
Antonella Castagna, MD - Designing Treatment Regimens to Suppress Multidrug-Resistant HIV: What Would You Do?
How manageable is multidrug-resistant keratitis? Find out about this and more in today's PV Roundup podcast.
Dr. John Fleetham chats with Dr. Molly Franke and Dr. James Brust about their articles, "Effectiveness of Bedaquiline Use Beyond Six Months in Patients with Multidrug-Resistant Tuberculosis" and “Weighting” the evidence: How much bedaquiline is enough?"
Multidrug-resistant organisms (MDROs) are a major concern for the nursing home population, who are at risk for developing severe infections. In today's episode, Quality Insights Medical Director Dr. Jean Storm discusses: The difference between colonization and active infection, and how this distinction should guide antibiotic prescribingClinical criteria that provide guidelines to determine what antibiotics are appropriateTools to guide assessment, aid communication, and determine best actionThis webinar is a rebroadcast of our episode that was recorded on March 15 and aired on March 17, 2023. Related links: Watch a Video Recording of This EpisodeDownload Presentation SlidesChoosing Wisely: Fifteen Things Physicians and Patients Should QuestionAHRQ's Suspected UTI SBAR toolkitCheck out our other interviews by visiting https://www.qualityinsights.org/qin/multimedia This material was prepared by Quality Insights, a Quality Innovation Network - Quality Improvement Organization under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services (HHS). Views expressed in this material do not necessarily reflect the official views or policy of CMS or HHS, and any reference to a specific product or entity herein does not constitute endorsement of that product or entity by CMS or HHS. Publication number 12SOW-QI-GEN-033023-CC-A
Multidrug-resistant organisms (MDROs) are a major concern for the nursing home population, who are at risk for developing severe infections. In today's episode, Quality Insights Medical Director Dr. Jean Storm discusses: The difference between colonization and active infection, and how this distinction should guide antibiotic prescribingClinical criteria that provide guidelines to determine what antibiotics are appropriateTools to guide assessment, aid communication, and determine best actionRelated links: Watch a Video Recording of This EpisodeDownload Presentation SlidesChoosing Wisely: Fifteen Things Physicians and Patients Should QuestionAHRQ's Suspected UTI SBAR toolkitCheck out our other interviews by visiting https://www.qualityinsights.org/qin/multimedia This material was prepared by Quality Insights, a Quality Innovation Network - Quality Improvement Organization under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services (HHS). Views expressed in this material do not necessarily reflect the official views or policy of CMS or HHS, and any reference to a specific product or entity herein does not constitute endorsement of that product or entity by CMS or HHS. Publication number 12SOW-QI-GEN-031623-CC-A
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
José R. Arribas, MD - Mastering the Management of Multidrug-Resistant HIV: When, With What, and How
¿Sabías qué patógenos super resistentes pueden estar contaminando los alimentos que nos comemos? Hoy en día, la resistencia de patógenos a antibióticos es uno de los problemas más importantes de salud pública a nivel mundial, ya que esto complica el uso y eficiencia de los antibióticos en tratamientos para combatir las enfermedades que estos generan. T4E10 *** REFERENCIAS DOF. (1997). NOM-040-ZOO-1995. Norma oficial mexicana, especificaciones para la comercialización de sales Puras antimicrobianas para uso en animales o consumo por estos. Retrieved from http://publico.senasica.gob.mx/?doc=516 Doyle, M. E. (2015). Multidrug-resistant pathogens in the food supply. Foodborne Pathogens and Disease, 12(4), 261–279. https://doi.org/10.1089/fpd.2014.1865 Duong, V. T., Nhu, T. D. H., Tuyen, H. T., Campbell, J. I., Van Minh, P., Le Phuc, H., & Baker, S. (2020). Genomic Serotyping, Clinical Manifestations, and Antimicrobial Resistance of Nontyphoidal Salmonella Gastroenteritis in Hospitalized Children in Ho Chi Minh City, Vietnam. Journal of Clinical Microbiology, 58(12), 1–15. Gebreyes, W. A., Wittum, T., Habing, G., Alali, W., Usui, M., & Suzuki, S. (2017). Spread of Antibiotic Resistance in Food Animal Production Systems. In Foodborne Diseases: Third Edition (Third Edit). https://doi.org/10.1016/B978-0-12-385007-2.00004-8 Godínez-Oviedo, A., Cabrera-Díaz, E., Palacios-Marmolejo, A., Pérez-Covarrubias, O.B Vargas Daniel, R., Tamplin, M. L., Bowman, J., & Hernández-Iturriaga, M. (2021). Detection, quantification, and characterization of Salmonella enterica in mango, tomato and raw chicken purchased in the central region of Mexico. Journal of Food Science, 87(1), 370-382. Tang, K. L., Caffrey, N. P., Nóbrega, D. B., Cork, S. C., Ronksley, P. E., Barkema, H. W., ... & Ghali, W. A. (2017). Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis. The Lancet Planetary Health, 1(8), e316-e327. OMS. 2017 Dejemos de administrar antibióticos a animales sanos para prevenir la propagación de la resistencia a los antimicrobianos. from https://www.who.int/es/news/item/07-11-2017-stop-using-antibiotics-in-healthy-animals-to-prevent-the-spread-of-antibiotic-resistance#:~:text=La%20Organizaci%C3%B3n%20Mundial%20de%20la,prevenir%20enfermedades%20en%20animales%20sanos. Parisi, A., Crump, J. A., Glass, K., Howden, B. P., Furuya-Kanamori, L., Vilkins, S., … Kirk, M. D. (2018). Health Outcomes from Multidrug-Resistant Salmonella Infections in High-Income Countries: A Systematic Review and Meta-Analysis. Foodborne Pathogens and Disease, 15(7), 428–436. https://doi.org/10.1089/fpd.2017.2403 WHO. (2015). FoodborneDiseaseBurden. Retrieved July 19, 2018, from https://extranet.who.int/sree/Reports?op=vs&path=/WHO_HQ_Reports/G36/PROD/EXT/FoodborneDiseaseBurden *** El podcast de Colectivo Motus es producido por MotusLab. El guion y la voz fueron realizados por Angélica Godínez Oviedo; la edición de audio por Nadia Cea y Vicente Castillo. La ilustración de portada, por Andrés Yánez. Agradecimientos a Emilio y Valeria Caltzontzin Rabell y Christopher Cedillo por la revisión y comentarios del contenido. APOYO DEL CONTENIDO, POR PARTE DE LA AUTORA El estudio mencionado en este episodio corresponde al aparte del trabajo de investigación financiado con el fondo FORDECYT-PRONACES/64377/2020, CONACYT *** ¡Sigue estas redes! Divulgación de la ciencia y a veces cosas de arte: https://www.instagram.com/colectivomotus El
Dr. Sergei Grando discusses his multidrug protocol shown to offer potential cure for the majority of pemphigus and pemphigoid patients.
'Something in the water' is the latest podcast from the Healthcare Infection Society journals.Gemma Winzor (University Hospitals Birmingham; Editor in Chief Infection Prevention in Practice) is joined by two fantastic guests: Mike Weinbren (NHS England and NHS improvement) and Teresa Inkster, (NHS greater Glasgow and Clyde, NHS Assure, and HCAI Scotland). The trio talk about the problems encountered in new-build healthcare facilities, training sub-specialties, and the infection prevention and control risks of water and waste water drains on augmented care - an area many find a bit daunting as it does not come up that often in day-to-day life as an infection control practitioner. Twitter: @jhieditor @IPIP_openEpisode links:Halstead et al. Pseudomonas aeruginosa infection in augmented care: the molecular ecology and transmission dynamics in four large UK hospitals. Journal of Hospital Infection, Volume 111, 162-168.Breathnach et al. Multidrug-resistant Pseudomonas aeruginosa outbreaks in two hospitals: association with contaminated hospital waste-water systems. Journal of Hospital Infection, Volume 82(1),19-24.Philip C. Carling. Wastewater drains: epidemiology and interventions in 23 carbapenem-resistant organism outbreaks. Infection Control & Hospital Epidemiology, Volume 39(8), 972-979.Find out more about the Healthcare Infection Society here Hosted on Acast. See acast.com/privacy for more information.
Drs. Kate DeSear (@IDPharmD_Kate) and Frank Tverdek (@FTverdek) join Dr. Julie Ann Justo (@julie_justo) to discuss the practice of empiric escalation in this episode of our gram-negative resistance series. Listen in for encouragement on following your intuition and tips on how, when, and why to practice this other side of antimicrobial stewardship. Learn more about the Society of Infectious Diseases Pharmacists: https://sidp.org/About Twitter: @SIDPharm (https://twitter.com/SIDPharm) Instagram: @SIDPharm (https://www.instagram.com/sidpharm/) Facebook: https://www.facebook.com/sidprx LinkedIn: https://www.linkedin.com/company/sidp/ References Clinical and Laboratory Standards Institute. Access Our Free Resources: M100 and M60. Accessed at https://clsi.org/standards/products/free-resources/access-our-free-resources/ Gallagher JC, et al. Open Forum Infect Dis. 2018 Oct 31;5(11):ofy280. doi: 10.1093/ofid/ofy280. PMID: 30488041. Castan B, et al. Infect Dis Now. 2021 Sep;51(6):532-539. doi: 10.1016/j.idnow.2021.05.003. Epub 2021 May 17. PMID: 34015539. Cultrera R, et al. Antibiotics (Basel). 2020 Sep 24;9(10):640. doi: 10.3390/antibiotics9100640. PMID: 32987821. Strich JR, et al. Clin Infect Dis. 2021 Feb 16;72(4):611-621. doi: 10.1093/cid/ciaa061. PMID: 32107536. Montravers P, Bassetti M. Curr Opin Infect Dis. 2018 Dec;31(6):587-593. doi: 10.1097/QCO.0000000000000490. PMID: 30299359. Strich JR, Heil EL, Masur H. J Infect Dis. 2020 Jul 21;222(Suppl 2):S119-S131. doi: 10.1093/infdis/jiaa221. PMID: 32691833. Kumar A, et al. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9. PMID: 16625125. Hibbard ML, et al. Surg Infect (Larchmt). 2010 Oct;11(5):427-32. doi: 10.1089/sur.2009.046. PMID: 20818984. Rosa RG, Goldani LZ, dos Santos RP. BMC Infect Dis. 2014 May 23;14:286. doi: 10.1186/1471-2334-14-286. PMID: 24884397. Benanti GE, et al. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01813-18. doi: 10.1128/AAC.01813-18. PMID: 30509935.
HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast
In this episode, we discuss six newer antibiotics that target multidrug resistant gram negative bacteria with Dr. Christie Bertram, PharmD, BCIDP. We review common resistance mechanisms, particularly to carbapenems, and highlight the current role in therapy for the following antibiotics: ceftolozane/tazobactam (Zerbaxa®), ceftazidime/avibactam (Avycaz®), meropenem/vaborbactam (Vabomere®), imipenem/cilastatin/relebactam (Recarbrio®), cefiderocol (Fetroja®), and eravacycline (Xerava®). Key Concepts Ceftolozane/tazobactam (Zerbaxa®) is primarily used for multidrug resistant Pseudomonas; it does not cover carbapenemase-producing organisms and (despite the tazobactam) needs metronidazole for intra-abdominal anaerobic coverage. Ceftazidime/avibactam (Avycaz®) is primarily used to cover CRE (Carbapenem-resistant Enterobacterales) but also has activity for many other gram negatives except Acinetobacter. Meropenem/vaborbactam (Vabomere®) has similar coverage to Avycaz® but may provide coverage for certain KPCs (Klebsiella pneumoniae carbapenemase). Vaborbactam does not restore activity for meropenem-resistant Pseudomonas. Imipenem/cilastatin/relebactam (Recarbrio®) has similar coverage to Avycaz® and Vabomere®; true niche in therapy is not yet well defined. Cefiderocol (Fetroja®) uses a unique mechanism to enter gram negative bacteria and has a broad spectrum of activity against carbapenemase-producing bacteria and many other multidrug resistant gram negatives. It has no gram positive activity. Eravacycline (Xerava®) is a tigecycline-like tetracycline with a broad spectrum of activity against carbapenemase-producing gram negative, gram positive, an anaerobic bacteria EXCEPT it lacks coverage for Pseudomonas. References Yusuf E, Bax HI, Verkaik NJ, van Westreenen M. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. J Clin Med. 2021;10(5):1068. Published 2021 Mar 4. doi:10.3390/jcm10051068 CDC Antibiotic Resistance Threats in the United States, 2019 report. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
Multidrug resistant tuberculosis is a public health crisis. In 2020, only 1 in 3 people with drug resistant TB accessed treatment. On this epsiode of Microbe Mail, Dr Sarah Stacey and I talk about treatment of MDR TB - why and how the regimens have changed, how to monitor patients on treatment and when to seek advice from an expert. https://sahivsoc.org/Files/management%20of%20rifampicin-resistant%20tb%20booklet%201219%20v6.pdf (South African Rifampicin Resistant TB Treatment Guidelines) About our Guest: Dr Sarah Stacey I am an infectious diseases specialist and I run a busy urban clinic at a tertiary site in Johannesburg and a busy infectious diseases ward – until a fire interrupted our services, that is… We are starting to get up and running again and hopefully will be back to capacity soon. The majority of our admissions to the infectious diseases ward are still HIV related and we still see advanced disease in patients never on or defaulting ART. I have a broad range of interests within the scope of infectious diseases. I have an interest in improving and simplifying diagnostic tests in TB, particularly in HIV-positive patients in whom TB diagnosis continues to be challenging. I also have a particular interest in advancing proper antimicrobial stewardship and the implementation of programmes to improve antibiotic prescribing. I founded the CMJAH Antimicrobial Stewardship Programme and I and my colleagues on the committee are in the process of expanding the programme at the hospital which can be at times both rewarding and thankless... but a worthwhile fight! instagram: sarahstacey15 twitter: @SarahLynnStace1 facebook: sarah.stacey.1297 Visit the Microbe Mail https://microbemail.captivate.fm/ (website) to sign up for updates E-mail: mail.microbe@gmail.com YouTube: https://www.youtube.com/channel/UCgaP3aUNkjrgOxR8Ei6UaEw (Microbe Mail) Instagram: https://instagram.com/https:/www.instagram.com/microbe_mail/ (Microbe_Mail) Facebook: Microbe Mail Twitter: @microbemail
On this week's episode we are discussing Tuberculosis, or TB. Currently the infection has a rate of infection that is only 2.2 per 100,000 persons. TB is more common in countries where many people live in absolute poverty because people are more likely to: live and work in poorly ventilated and overcrowded conditions, which provide ideal conditions for TB bacteria to spread suffer from malnutrition and disease – particularly HIV – which reduces resistance to TB have limited access to healthcare – and just one person with untreated infectious TB can pass the illness on to 10-15 people annually. Other TB Facts: A total of 1.5 million people died from TB in 2020 (including 214 000 people with HIV). Worldwide, TB is the 13th leading cause of death and the second leading infectious killer after COVID-19 (above HIV/AIDS). In 2020, an estimated 10 million people fell ill with tuberculosis (TB) worldwide. 5.6 million men, 3.3 million women and 1.1 million children. TB is present in all countries and age groups. But TB is curable and preventable. In 2020, 1.1 million children fell ill with TB globally. Child and adolescent TB is often overlooked by health providers and can be difficult to diagnose and treat. In 2020, the 30 high TB burden countries accounted for 86% of new TB cases. Eight countries account for two thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. Only about one in three people with drug resistant TB accessed treatment in 2020. Globally, TB incidence is falling at about 2% per year and between 2015 and 2020 the cumulative reduction was 11%. This was over half way to the End TB Strategy milestone of 20% reduction between 2015 and 2020. An estimated 66 million lives were saved through TB diagnosis and treatment between 2000 and 2020. Globally, close to one in two TB-affected households face costs higher than 20% of their household income, according to latest national TB patient cost survey data. The world did not reach the milestone of 0% TB patients and their households facing catastrophic costs as a result of TB disease by 2020. By 2022, US$ 13 billion is needed annually for TB prevention, diagnosis, treatment and care to achieve the global target agreed at the UN high level-meeting on TB in 2018. Funding in low- and middle-income countries (LMICs) that account for 98% of reported TB cases falls far short of what is needed. Spending in 2020 amounted to US$ 5.3 billion less than half (41%) of the global target. There was an 8.7% decline in spending between 2019 and 2020 (from US$ 5.8 billion to US$ 5.3 billion), with TB funding in 2020 back to the level of 2016. Ending the TB epidemic by 2030 is among the health targets of the United Nations Sustainable Development Goals (SDGs). Tuberculosis (TB) is caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs. Tuberculosis is curable and preventable. TB is spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected. About one-quarter of the world's population has a TB infection, which means people have been infected by TB bacteria but are not (yet) ill with the disease and cannot transmit it. People infected with TB bacteria have a 5–10% lifetime risk of falling ill with TB. Those with compromised immune systems, such as people living with HIV, malnutrition or diabetes, or people who use tobacco, have a higher risk of falling ill. When a person develops active TB disease, the symptoms (such as cough, fever, night sweats, or weight loss) may be mild for many months. This can lead to delays in seeking care, and results in transmission of the bacteria to others. People with active TB can infect 5–15 other people through close contact over the course of a year. Without proper treatment, 45% of HIV-negative people with TB on average and nearly all HIV-positive people with TB will die. Who is most at risk? Tuberculosis mostly affects adults in their most productive years. However, all age groups are at risk. Over 95% of cases and deaths are in developing countries. People who are infected with HIV are 18 times more likely to develop active TB (see TB and HIV section below). The risk of active TB is also greater in persons suffering from other conditions that impair the immune system. People with undernutrition are 3 times more at risk. Globally in 2020, there were 1.9 million new TB cases that were attributable to undernutrition. Alcohol use disorder and tobacco smoking increase the risk of TB disease by a factor of 3.3 and 1.6, respectively. In 2020, 0.74 million new TB cases worldwide were attributable to alcohol use disorder and 0.73 million were attributable to smoking. Global impact of TB TB occurs in every part of the world. In 2020, the largest number of new TB cases occurred in the WHO South-East Asian Region, with 43% of new cases, followed by the WHO African Region, with 25% of new cases and the WHO Western Pacific with 18%. In 2020, 86% of new TB cases occurred in the 30 high TB burden countries. Eight countries accounted for two thirds of the new TB cases: India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. Symptoms and diagnosis Common symptoms of active lung TB are cough with sputum and blood at times, chest pains, weakness, weight loss, fever and night sweats. WHO recommends the use of rapid molecular diagnostic tests as the initial diagnostic test in all persons with signs and symptoms of TB as they have high diagnostic accuracy and will lead to major improvements in the early detection of TB and drug-resistant TB. Rapid tests recommended by WHO are the Xpert MTB/RIF Ultra and Truenat assays. Diagnosing multidrug-resistant and other resistant forms of TB (see Multidrug-resistant TB section below) as well as HIV-associated TB can be complex and expensive. Tuberculosis is particularly difficult to diagnose in children. Treatment TB is a treatable and curable disease. Active, drug-susceptible TB disease is treated with a standard 6-month course of 4 antimicrobial drugs that are provided with information and support to the patient by a health worker or trained volunteer. Without such support, treatment adherence is more difficult. Since 2000, an estimated 66 million lives were saved through TB diagnosis and treatment. (credits: WHO)
Bacteriophages are interesting viruses that target bacteria and have been used for therapeutic purposes. Recently, the emergence of antibiotic resistance has spurred a renewed interest in using these viruses or their products as therapeutic tools against recalcitrant human pathogens. AAC has also published a recent manuscript from ARLG to guide the use of phages in clinical practice. We will discuss with experts in the field the state-of-the-art in phage therapy. Objectives: • Understand the use of bacteriophages and their products for therapeutic purposes • Discuss the clinical applications of phages • Debate the barriers for developing of phages as therapeutic tools to treat multidrug-resistant infections Guests: • Vincent A. Fischetti, Ph.D, Professor and Director, Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY. • Saima Aslam, MBBS, Professor of Medicine, University of California San Diego, San Diego, CA. • Anthony Maresso, PhD. Professor and Founder of TAILOR Labs, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX. This episode of Editors in Conversation is brought to you by the Antimicrobial Agents and Chemotherapy Journal and hosted by AAC Editor in Chief, Cesar Arias. AAC is available at https://asm.org/aac. Follow Cesar on twitter at https://twitter.com/SuperBugDoc for AAC updates. Subscribe to the podcast at https://asm.org/eic
Where are we now with multidrug resistance? Join experts Dr Gupta and Dr Huldrych to find out. Credit available for this activity expires: 2/22/2023 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/967537?src=mkm_podcast_addon_967537
Dr. Paul Planet, an assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and at Children's Hospital Philadelphia, as well as a senior researcher at the Sackler Institute for Comparative Genomics at the American Museum of Natural History in New York, and Sarah Gregory discuss multidrug-resistant MRSA in Rio de Janeiro, Brazil.
Medical technology and precision medicine have come a long way, and many people assume that the process of researching, discovering, and producing new drugs has never been easier. What if you learned that the last entirely original class of antibiotic was discovered in the late 1980s? In this episode of the Public Health Insight Podcast, Mr. Schacht remains to discuss:Geographical distribution of antimicrobial resistant (AMR) infectionsWhy big pharma no longer prioritizes the research and development of new antibiotics or other antimicrobials; and The need for coordinated multi-sectoral approaches to tackle AMR as a top ten global threat.Podcast GuestsOliver SchachtPodcast HostsWilliam Wang, BA, MPHGordon Thane, BMSc, MPH, PMP®References for Our Discussion World Economic Forum: The looming health catastrophe that could be more deadly than COVID-19World Health Organization: Antimicrobial resistanceSubscribe to the NewsletterWhat if there was an easy way to receive timely information about public health and global health right to your inbox? Subscribe to the newsletter to stay in the loop about the latest news, live events, jobs, and professional development opportunities. Subscribe to ensure you don't miss out: https://thepublichealthinsight.com/subscribe/. Tell A FriendIf you enjoy our podcasts, it would mean the world if you shared it on social media and tagged us. If you are not the social media type, we would appreciate it if you shared it with a friend or colleague who you think might enjoy the podcast. It helps us to get discovered by other people.
Living With Multidrug-Resistant HIV: What Clinicians Need to Know
Living With Multidrug-Resistant HIV: What Clinicians Need to Know
Living With Multidrug-Resistant HIV: What Clinicians Need to Know
Living With Multidrug-Resistant HIV: What Clinicians Need to Know
In this episode we open up by discussing the terrible floods in Germany, the claims made by esoterics and how you can help. We also note that covid misinformation numbskull Sucharit Bhakdi has lost his publisher for being an anti-Semite. In the This Week we talk about Gregor Mendel and then we hear that Pope Francis is now openly challenging his predecessor Benedict. The we go through the news: - Vaccine protests in Cyprus - Organized tour of Sweden by anti-vaxxers - Multidrug-resistant bacteria found in dog raw-food - Greenland suspends oil exploration because of climate change - Man behind one of the Muhammad caricatures dead - Macchiarini follow-up – whistle-blowers file complaint with the Strasbourg Court Polish researcher Harald Walach gets today's prize for being Really Wrong after trying to say that masks and covid vaccinations are dangerous. Enjoy! The Events Calendar: https://theesp.eu/events_in_europe
This Canada Day, let's remember: this country was built on genocide | Mumilaaq Qaqqaq | The GuardianStarship - We Built This City (Official Music Video) - YouTubeThe Tragically Hip - WikipediaSecret Path - WikipediaLong Time Running - WikipediaLong Time Running - OFFICIAL TRAILER HD - YouTubeNeil Young - Long May You Run (unplugged) - YouTubeDon't Forget To Cast A Vote For Milltown's Most Patriotic House | TAPintoMilltown's Most Patriotic House 2021 - PollMilltown 4th of JulyAbbey Lane in North Raleigh is home to some of the best Christmas lights in the Triangle - ABC11 Raleigh-DurhamStonehenge - WikipediaClick & Collect - WikipediaMythic Quest - WikipediaHome Security Systems | Smart Home Automation | RingFood Safety Talk 2021 graphic teeVenomous spitting cobra on the loose in Raleigh, North Carolina neighborhood - CBS NewsOwner of missing zebra cobra previously bitten by green mamba snake, saved by Riverbanks ZooHouse of Swank BBQ shirtsHouse of Swank Cobra shirtsInternational Association for Food Protection annual meetingCDC COVID Data TrackerSARS-CoV-2 Variant Classifications and DefinitionsExpert says NC State baseball team cluster indicates rapid spread of Delta strainInformation Regarding Return to Campus for Rutgers–New Brunswick - Universitywide COVID-19 InformationHome Food Safety: 3 Common Kitchen Habits That Spread Germs | Apartment TherapyFYI, Your Kitchen Is Probably Dirtier than a Toilet Seat | Food & WineFood Safety Tips for Healthy Holidays | FDA131. Not Following the FDA Model Food Code Handwashing Directions — Risky or Not?Fresh Human-Grade Dog Food Delivery | The Farmer's DogDigest | Better living with your dogDogs | Healthy Pets, Healthy People | CDCIn France, Our Dog Has His Day - The New York Times120. A Dog Licking Your Plate — Risky or Not?Blah, Blah, Blah, Blah Ginger | Thinking it ThroughOutbreak of Multidrug-resistant Campylobacter Infections Linked to Contact with Pet Store Puppies | CDCFood Safety TalkRecipes - Texas Cottage Food LawAbout - Texas Cottage Food Law
The Beyond Clean GoldMind is a free innovative digital dictionary resource for Sterile Processing terms, featuring diverse voices from around the globe who provide definitions to the most common terms in our industry. Releasing 365 days a year, GoldMind is your daily dose of Sterile Processing education and insight to invest in yourself, your future, and the safety of your patient. It is a perfect addition to new technician on-boarding, certification studies, and educational programming in your facility. For more creative Sterile Processing education & resources, visit us at http://www.beyondclean.net #GoldMind #BeyondClean #DigitalDictionary #WordOfTheDay #Education #SterileProcessing #Voices #Network #Listen #Learn #ChangeTheWorld
A 10 year partnership between UL and HSE has benefited patients dealing with multidrug-resistant infections, patients with cystic fibrosis and those with chronic obstructive pulmonary disease (COPD). Winner of the 2020 Outstanding Research Collaboration, President’s Research Excellence and Impact Award, the collaboration involves microbiologists, designers, engineers, nurses, physiotherapists, paediatricians, respiratory specialists. Understanding infectious disease outbreaks and the microbial causes of infection leads to new prevention and control interventions, education programmes and innovations in medical device and testing technologies. Prof Colum Dunne, School of Medicine, Prof Barry Linnane, Consultant Respiratory Paediatrician, UHL, Prof Nuala O’Connell, Consultant Clinical Microbiologist, UHL, Barbara Slevin, Assistant Director of Nursing, Infection Prevention & Control, ULHG, Kevin O’Sullivan, Rapid Innovation Unit and Prof Colum Dunne, School of Medicine UL join our host Prof of Economics, Helena Lenihan to discuss their award-winning collaboration. Supporting the UN Sustainable Development Goals.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.15.383794v1?rss=1 Authors: Kapoor, k., Pant, S., Tajkhorshid, E. Abstract: P-glycoprotein (Pgp) is a major efflux pump in humans, overexpressed in a variety of cancers and associated with the development of multi-drug resistance. Allosteric modulation induced by binding of various ligands (e.g., transport substrates, inhibitors, and ATP) has been bio-chemically shown to directly influence the function of Pgp. However, the molecular details of such effects are not well established. In particular, the role and involvement of the sur-rounding lipid environment on ligand-induced modulation of the conformational dynamics of the transporter have not been investigated at any level. Here, we employ all-atom molecular dynamics (MD) simulations to study the conformational landscape of Pgp in the presence of a high-affinity, third-generation inhibitor, tariquidar, in comparison to the nucleotide-free (APO) and the ATP-bound states, in order to shed light on and to characterize how the inhibitor blocks the function of the transporter. Simulations in a multi-component lipid bi-layer show a dynamic equilibrium between open and closed inward-facing (IF) conformations in the APO-state, with binding of ATP shifting the equilibrium towards conformations feasible for ATP hydrolysis and subsequent completion of the transport cycle. In the presence of the inhibitor bound to the drug-binding pocket in the transmembrane domain (TMD), the transporter samples more open IF conformations, and the nucleotide binding domains (NBDs) are observed to become highly dynamic. Interestingly, and reproduced in multiple independent simulations, the inhibitor is observed to recruit lipid molecules into the Pgp lumen through the two proposed drug-entry portals, where the lipid head groups from the lower leaflet translocate inside the TMD, while the lipids tails remain extended into the bulk lipid environment. These 'wedge-lipid' molecules likely enhance the inhibitor-induced conformational changes in the TMD leading to the differential modulation of coupling pathways observed with the NBDs downstream. We suggest a novel inhibitory mechanism for tariquidar, and for related third-generation Pgp inhibitors, where lipids are seen to enhance the inhibitory role in the catalytic cycle of membrane transporters. Copy rights belong to original authors. Visit the link for more info
呼吸科星期二 2020年11月3日 第2集FDA 免疫检查点抑制剂进入肺癌的一线治疗NEJM 治疗耐药结核时，短疗程方案不劣于长疗程方案Cell CT的人工智能系统可用于诊断COVID-19德瓦鲁单抗（durvalumab）德瓦鲁单抗是一种PD-L1单抗，此前已被批准用于治疗晚期膀胱癌和无法切除的3期非小细胞肺癌。2020年3月，德瓦鲁单抗被批准用于广泛期小细胞肺癌联合标准化疗的一线用药。《CASPIAN研究：德瓦鲁单抗联合铂-依托泊苷治疗广泛期小细胞肺癌的疗效》Lancet，2019年11月 (1)这项研究的目的是评估德瓦鲁单抗与依托泊苷联合顺铂或卡铂治疗广泛期小细胞肺癌的疗效，对照组方案是依托泊苷联合顺铂或卡铂。这项随机、开放标签、三期试验，纳入未经治疗的、广泛期小细胞肺癌患者537人，随机分为德瓦鲁单抗+铂/依托泊苷组、铂/依托泊苷组。联合德瓦鲁单抗组总生存率显著改善，优势比为0·73（p = 0·0047）。联合德瓦鲁单抗组和不使用德瓦鲁单抗组中，中位总生存期分别为13·0个月和10·3个月；随访至18个月时，两组分别有34%和25%的患者存活。结论：一线德瓦鲁单抗联合铂/依托泊苷显著改善广泛期小细胞肺癌患者的总生存率。纳武利尤单抗+ 伊匹木单抗（nivolumab+ipilimumab）2020年5月，FDA批准纳武利尤单抗（抗PD-1单抗）和伊匹木单抗（CTLA-4单抗），两个药物联合低剂量化疗作为转移或复发的非小细胞肺癌的一线治疗方案。《CheckMate 227研究：纳武利尤单抗联合伊匹木单抗治疗晚期非小细胞肺癌的3期临床研究》New England of Medicine，2019年11月 (2)此项开放标签的3期临床研究的目的是，评价晚期非小细胞肺癌患者中使用PD-1单抗（纳武利尤单抗）+CTLA-4单抗（伊匹木单抗）联合治疗的长期获益。研究纳入PD-L1表达水平≥1%的、Ⅳ期或复发的、非小细胞肺癌患者，随机分入纳武利尤单抗+伊匹木单抗双联治疗组、或纳武利尤单抗单药治疗、或化疗组；同时也纳入了PD-L1表达水平＜1%的患者，随机分三组中。所有患者之前均未接受过化疗。在PD-L1表达水平≥1%的患者中，纳武利尤单抗+伊匹木单抗组和化疗组的中位总生存期分别为17.1个月和14.9个月（P=0.007），2年总生存率分别为40.0%和32.8%，中位缓解时间分别为23.2个月和6.2个月。在PD-L1表达水平＜1%的患者中也观察到了总生存期获益，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.2个月和12.2个月。全部患者中，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月和13.9个月，严重不良事件发病率分别为32.8%和36.0%。结论：在非小细胞肺癌患者中，纳武利尤单抗+伊匹木单抗一线治疗组的总生存期超过化疗组，且与PD-L1表达水平无关。长期随访中未发现新的安全性问题。阻塞性睡眠呼吸暂停阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是一种因睡眠过程中上气道反复塌陷引起的、以阻塞性呼吸暂停和低通气为特征的疾病。对于存在白天睡眠过多、打鼾和睡眠中窒息或倒吸气等症状的、高龄、肥胖、男性患者，应该考虑这个诊断。多导睡眠监测图是诊断的金标准，诊断标准为：无相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥15次/小时；伴有相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥5次/小时。相关症状包括：嗜睡、疲劳、失眠，觉醒时存在憋气、倒吸气或窒息，或者观察者发现患者习惯性打鼾、呼吸中断。相关疾病包括：高血压、心境障碍、认知功能障碍、冠心病、脑卒中、心力衰竭、心房颤动或2型糖尿病。《前瞻性研究：睡眠呼吸障碍和失眠与高血压和糖尿病的关系》American Journal of Respiratory and Critical Care Medicine，2020年7月 (3)这项前瞻性研究，通过长达6年的随访，旨在调查美国西班牙裔/拉丁裔人群中，睡眠呼吸障碍和失眠与高血压和糖尿病发生之间的关联，共纳入11623名参与者，女性占52.6％，平均年龄41.1±14.9岁。存在睡眠呼吸障碍的人群，与没有睡眠呼吸障碍的人群比较，高血压发生的风险比1.54，糖尿病发生风险比1.37。失眠与高血压有关（风险比1.37），其中男性关联性更强。结论：睡眠呼吸障碍与高血压和糖尿病有关。失眠与高血压有关。这些结果支持将睡眠障碍作为预防和减少高血压、糖尿病的靶标。《SAVE研究：持续气道正压治疗对同时患有OSA和稳定性冠心病的患者的糖尿病的影响》Diabetes Care，2020年7月 (4)研究试图确定在同时患有稳定性冠心病和OSA患者中，长期持续气道正压（CPAP）通气治疗对血糖控制和糖尿病风险的影响。研究收集了888名同时患有稳定性冠心病和OSA患者，一组接受CPAP加常规治疗，另一组接受常规治疗，中位随访时间为4.3年。糖尿病的患者中，不同治疗组的血糖、糖化血红蛋白或降糖药物使用方面无显著差异。糖尿病前期、或新诊断的糖尿病患者中，组间也没有显著差异。有趣的是，女性糖尿病患者在常规治疗组表现较差，而接受CPAP治疗后病情更稳定。结论：在同时患有稳定性冠心病和OSA患者中，尚无证据证明长期CPAP治疗对血糖控制有益。但研究中发现的性别差异仍需进一步验证。阻塞性睡眠呼吸暂停的治疗一般治疗包括：减重、运动、侧卧位睡眠、避免酒精、避免使用精神类药物。主要治疗方法是气道正压治疗，常见模式包括持续气道正压（CPAP）、双水平气道正压（BPAP）和自动调定式的气道正压（APAP），最常用的是CPAP。替代治疗方法包括：轻中度患者可尝试口腔矫正器、存在上气道阻塞的患者可尝试上气道外科手术、也可尝试直接或间接刺激呼吸驱动的药物（如茶碱或乙酰唑胺）、或减少上气道塌陷的药物（如地昔帕明）。《对照研究：腭舌手术治疗中重度阻塞性睡眠呼吸暂停的患者》JAMA，2020年9月 (5)研究的目的是考察了腭舌手术对阻塞性睡眠呼吸暂停综合征（OSA）常规治疗失败患者的疗效。研究纳入常规治疗失败的、症状性的、中重度、阻塞性睡眠呼吸暂停患者101人，随机接受多次腭舌手术（改良悬雍垂腭咽成形术和微创舌体积缩小术）、或常规医疗（例如，改善睡眠姿势或减肥）。89%的患者完成了试验，手术组基线时的平均睡眠呼吸暂停低通气指数为47.9，6个月时为20.8；常规医疗组基线时为45.3，6个月时为34.5（6个月时，组间平均校正后差异为-17.6个事件/小时）。手术组基线时的Epworth嗜睡评分为12.4，6个月时为5.3；常规医疗组基线时为11.1，6个月时为10.5（6个月时，平均基线调整组间差异-6.7）。不良事件：手术组1例术后第5天发生心肌梗死，1例因吐血而住院观察。结论：常规治疗失败的、中重度阻塞性睡眠呼吸暂停症患者，接受悬雍垂腭咽成形术和微创舌体积缩小术，可减少呼吸暂停和低通气事件的发生，改善患者嗜睡症状。肺结核肺结核是结核分枝杆菌感染最常见的部位。（1）原发性肺结核主要发生于儿童期，也可以在青少年或成人中发生，其临床表现在人群中差异很大：低热70%、胸膜炎性胸痛25%、乏力咳嗽咽痛比较少见。X线表现：肺门淋巴结肿大65%，胸腔积液33%，肺部浸润27%。原发性感染后，90%的免疫系统正常者可以控制结核杆菌的进一步复制；随后结核杆菌可能进入潜伏期，10%的感染者进行性的出现肺结核肺炎。（2）复燃性肺结核的患者发热和盗汗更常见，约一半的患者有咳嗽、体重减轻、乏力。X线表现：上叶尖后段受累80-90%，空洞形成20%。《系统回顾和荟萃分析：近距离接触结核病人后，儿童罹患肺结核的风险》Lancet，2020年3月 (6)全球每年有数千万儿童接触结核分枝杆菌，但是，仍没有对受感染儿童罹患结核病的风险的估计，对接触调查和预防治疗的有效性也缺乏了解。在这篇系统回顾和荟萃分析中，纳入了来自34个国家的46个队列研究的数据。评估了137647例结核暴露儿童，对135512例儿童进行了429538人年随访，期间诊断出1299例流行性结核和999例散发性结核。结核感染阳性、但未接受预防治疗的儿童2年累计肺结核发病率明显高于结核感染阴性儿童。其中5岁以下儿童肺结核发病率最高，为19·0%。所有暴露儿童预防治疗的有效性为63%，对于结核感染阳性儿童预防治疗的有效性为91%。结论：结核暴露的婴儿和幼儿罹患结核病的风险非常高，大多数病例发生在接触者调查开始后的几周内。《前瞻性研究：接触耐多药结核病后异烟肼的防治效果》American Journal of Respiratory and Critical Care Medicine，2020年6月 (7)WHO建议单独使用异烟肼或异烟肼与利福平联合使用来治疗潜在的结核病感染。该研究的目的是研究单独使用异烟肼用于预防多药耐药结核感染的有效性。这个前瞻性群组研究纳入4500个肺结核病人和14044个结核暴露家庭，19岁以下的接触者共4216人，只有一半人接受了异烟肼预防治疗。异烟肼的预防作用十分显著，在接触非耐药结核病人时感染风险下降70%，在接触多药耐药结核病人后的感染风险下降81%。在接触异烟肼单药耐药结核病人时，异烟肼的预防作用稍弱（风险比0.80）。在第二项独立研究中，76名接受异烟肼预防的家庭接触者均未感染；而273名未接受异烟肼预防治疗的家庭接触者有8人感染，占3%。结论：即使接触多药耐药结核病患者，异烟肼也能有效降低接触者的结核发病率。《随机对照研究：补充维生素D预防结核杆菌感染》New England Journal of Medicine，2020年7月 (8)研究的目的是评估补充维生素D是否可以预防结核病感染。参与研究的8851名、结核分枝杆菌感染阴性的、维生素D缺乏的儿童，随机分入维生素D组或安慰剂组，干预持续3年。3年后，儿童的维生素D缺乏得到纠正，两组的平均25-羟-维生素D水平分别为31.0ng/mL和10.7ng/mL；但是两组间QuantiFERON-TB试验阳性比例没有差异，分别为3.6%和3.3%（P = 0.42）。维生素D组有21名儿童和安慰剂组有25名儿童被诊断患有结核病，分别有29人和34人因急性呼吸道感染住院治疗，发生率无显著差异。结论：维生素D缺乏的儿童中，补充维生素D没有降低结核感染的风险。肺结核的治疗无HIV感染的、成人的药物敏感性的、肺结核治疗：通常2个月强化治疗以及4-7个月维持治疗。强化阶段通常采用四联药物治疗 [ 包括异烟肼、利福霉素类（利福平、利福喷丁、利福布丁）、吡嗪酰胺、乙胺丁醇 ] ，维持治疗通常采用二联药物治疗（包括异烟肼、利福平）。耐药肺结核包括单药耐药和多药耐药。单药耐药的情况下，可选用其他的一线药物，也可联合氟喹诺酮类。多药耐药的治疗取决于药敏试验，原则是尽可能多的一线药物，再加上一种氟喹诺酮类（左氧氟沙星、莫西沙星）和/或另一种核心二线药物（如贝达喹啉、利奈唑胺）。药物研发进展：普托马尼（pretomanid，硝基咪唑嗪类抗菌药，2019年8月批准上市）。《随机研究：短疗程治疗利福平耐药的肺结核的3期临床研究》New England Journal of Medicine，2019年3月 (9)研究的目的是在对氟喹诺酮类和氨基糖苷类药物敏感的、利福平耐药的、结核患者中开展了一项3期非劣效性试验。共424例患者，随机分别接受含有大剂量莫⻄沙星的短疗程方案（9~11个月）或遵循2011年WHO指南推荐的⻓疗程方案（20个月）。132周后，⻓疗程方案组和短疗程方案中，分别有79.8%和78.8%的参与者报告了良好状态（P=0.02）。两组的严重不良事件发生率分别有45.4%和48.2%。短疗程方案组11.0%参与者和⻓疗程方案组6.4%参与者出现QT间期延⻓，并进行了药物调整。结论：在对氟喹诺酮类药物和氨基糖苷类药物敏感的、利福平耐药的结核患者中，包括大剂量莫西沙星的短疗程方案的主要疗效结局不劣于⻓疗程方案，安全性相似。支气管热成型术支气管热成形术（Bronchial Themoplasty）是一种治疗重度哮喘的手段，经由纤维光学支气管镜导入特质的导管，然后利用该导管对支气管壁施加热能，以削弱支气管平滑肌的收缩力、减轻气道平滑肌的增生。该操作通常需要在中度镇静下进行3次支气管镜下操作，每次间隔3周。主要针对的人群是治疗吸入性糖皮质激素和LABA控制不佳的、重症哮喘患者。但这项操作有风险，对其长期的疗效仍有一定的争议。《TASMA研究：支气管热成型术引起的气道平滑肌减少和对重症哮喘的治疗效果》American Journal of Respiratory and Critical Care Medicine，2020年7月(10)研究的目的是确定支气管热成型术对气道平滑肌的质量的影响，并确定哪一类重症哮喘患者适合接受此项治疗。研究纳入40例重症哮喘患者，随机分为即时支气管热成型术组和延迟支气管热成型术组。即时手术组的中位气道平滑肌质量减少>50%，而延迟组的气管平滑肌的质量无变化（p=0.0004）。即时手术组和延迟手术组中，哮喘控制问卷评分分别降低了0.79和升高了0.09（p=0.006）；哮喘生活质量问卷评分分别升高了0.83和降低了0.02（p=0.04）。治疗反应（n=35）与血清IgE和嗜酸性粒细胞呈正相关，但与气道平滑肌基线质量无关。结论：支气管热成型术后气道平滑肌的质量明显降低。疗效与血清IgE和嗜酸性粒细胞水平相关，而与气道平滑肌的质量无关。《随机对照临床研究：129Xe-MRI引导的一次支气管热成形术》American Journal of Respiratory and Critical Care Medicine，2020年8月 (11)不良事件限制了支气管热成形术在重症哮喘中的应用，该研究的目的是使用氙129磁共振技术（129Xe-MRI）引导下进行支气管热成形术。研究对30例严重哮喘患者进行容积CT和129Xe-MRI，以定量节段性通气缺损，然后被随机分组至磁共振引导组（行一次支气管热成形术治疗6个病变最严重的支气管）、或非引导组（标准的三阶段支气管热成形术）。治疗12周后，磁共振引导组与非引导组相比，生活质量评分改善无显著差异（P = 0.201），但肺通气不良和肺不通气的比例下降更显著（-17.2%；P = 0.009）。磁共振引导组中33%的患者术后哮喘加重；非引导组有73%的患者哮喘加重（P = 0.028）。结论：与标准的三次支气管热成形术相比，磁共振引导下的一次支气管热成形术可以取得类似的短期改善，且围手术期不良事件较少。CT诊断人工智能系统《应用人工智能系统对新型冠状病毒肺炎进行CT诊断、定量和预后评估》 Cell，2020年6月 (12)许多罹患COVID-19的患者发展为肺炎，并迅速发展为呼吸衰竭。然而，快速诊断与鉴别高危患者、并早期干预仍十分具有挑战性。使用大型CT数据库分析4154名患者的资料后，研究人员开发了用以诊断和鉴别诊断新型冠状病毒肺炎的人工智能系统。此人工智能系统能够客观、定量的识别和测量新型冠状病毒肺炎病变CT上的肺部损害指标，如小结节、毛玻璃影、实变影，评价疾病严重程度，也可用于客观、定量的评价药物有效性。结合患者临床指标，如吸氧频率、血氧饱和度、血气分析、肝功能、凝血功能等，可以综合分析并预测患者发展为危重症的可能性和时间。参考文献1.Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. 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New England Journal of Medicine. 2019;380(13):1201-13.9.Huang CC, Becerra MC, Calderon R, Contreras C, Galea J, Grandjean L, et al. Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis. Am J Respir Crit Care Med. 2020.10.Goorsenberg AWM, d'Hooghe JNS, Srikanthan K, Ten Hacken NHT, Weersink EJM, Roelofs J, et al. Bronchial Thermoplasty Induced Airway Smooth Muscle Reduction and Clinical Response in Severe Asthma: The TASMA Randomized Trial. Am J Respir Crit Care Med. 2020.11.Hall CS, Quirk JD, Goss CW, Lew D, Kozlowski J, Thomen RP, et al. Single-Session Bronchial Thermoplasty Guided by (129)Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2020;202(4):524-34.12.Zhang K, Liu X, Shen J, Li Z, Sang Y, Wu X, et al. Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography. Cell. 2020;181(6):1423-33 e11.
呼吸科星期二 2020年11月3日 第2集FDA 免疫检查点抑制剂进入肺癌的一线治疗NEJM 治疗耐药结核时，短疗程方案不劣于长疗程方案Cell CT的人工智能系统可用于诊断COVID-19德瓦鲁单抗（durvalumab）德瓦鲁单抗是一种PD-L1单抗，此前已被批准用于治疗晚期膀胱癌和无法切除的3期非小细胞肺癌。2020年3月，德瓦鲁单抗被批准用于广泛期小细胞肺癌联合标准化疗的一线用药。《CASPIAN研究：德瓦鲁单抗联合铂-依托泊苷治疗广泛期小细胞肺癌的疗效》Lancet，2019年11月 (1)这项研究的目的是评估德瓦鲁单抗与依托泊苷联合顺铂或卡铂治疗广泛期小细胞肺癌的疗效，对照组方案是依托泊苷联合顺铂或卡铂。这项随机、开放标签、三期试验，纳入未经治疗的、广泛期小细胞肺癌患者537人，随机分为德瓦鲁单抗+铂/依托泊苷组、铂/依托泊苷组。联合德瓦鲁单抗组总生存率显著改善，优势比为0·73（p = 0·0047）。联合德瓦鲁单抗组和不使用德瓦鲁单抗组中，中位总生存期分别为13·0个月和10·3个月；随访至18个月时，两组分别有34%和25%的患者存活。结论：一线德瓦鲁单抗联合铂/依托泊苷显著改善广泛期小细胞肺癌患者的总生存率。纳武利尤单抗+ 伊匹木单抗（nivolumab+ipilimumab）2020年5月，FDA批准纳武利尤单抗（抗PD-1单抗）和伊匹木单抗（CTLA-4单抗），两个药物联合低剂量化疗作为转移或复发的非小细胞肺癌的一线治疗方案。《CheckMate 227研究：纳武利尤单抗联合伊匹木单抗治疗晚期非小细胞肺癌的3期临床研究》New England of Medicine，2019年11月 (2)此项开放标签的3期临床研究的目的是，评价晚期非小细胞肺癌患者中使用PD-1单抗（纳武利尤单抗）+CTLA-4单抗（伊匹木单抗）联合治疗的长期获益。研究纳入PD-L1表达水平≥1%的、Ⅳ期或复发的、非小细胞肺癌患者，随机分入纳武利尤单抗+伊匹木单抗双联治疗组、或纳武利尤单抗单药治疗、或化疗组；同时也纳入了PD-L1表达水平＜1%的患者，随机分三组中。所有患者之前均未接受过化疗。在PD-L1表达水平≥1%的患者中，纳武利尤单抗+伊匹木单抗组和化疗组的中位总生存期分别为17.1个月和14.9个月（P=0.007），2年总生存率分别为40.0%和32.8%，中位缓解时间分别为23.2个月和6.2个月。在PD-L1表达水平＜1%的患者中也观察到了总生存期获益，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.2个月和12.2个月。全部患者中，纳武利尤单抗+伊匹单抗组和化疗组的中位总生存期分别为17.1个月和13.9个月，严重不良事件发病率分别为32.8%和36.0%。结论：在非小细胞肺癌患者中，纳武利尤单抗+伊匹木单抗一线治疗组的总生存期超过化疗组，且与PD-L1表达水平无关。长期随访中未发现新的安全性问题。阻塞性睡眠呼吸暂停阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是一种因睡眠过程中上气道反复塌陷引起的、以阻塞性呼吸暂停和低通气为特征的疾病。对于存在白天睡眠过多、打鼾和睡眠中窒息或倒吸气等症状的、高龄、肥胖、男性患者，应该考虑这个诊断。多导睡眠监测图是诊断的金标准，诊断标准为：无相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥15次/小时；伴有相关疾病或症状者，睡眠期间阻塞性为主的呼吸事件≥5次/小时。相关症状包括：嗜睡、疲劳、失眠，觉醒时存在憋气、倒吸气或窒息，或者观察者发现患者习惯性打鼾、呼吸中断。相关疾病包括：高血压、心境障碍、认知功能障碍、冠心病、脑卒中、心力衰竭、心房颤动或2型糖尿病。《前瞻性研究：睡眠呼吸障碍和失眠与高血压和糖尿病的关系》American Journal of Respiratory and Critical Care Medicine，2020年7月 (3)这项前瞻性研究，通过长达6年的随访，旨在调查美国西班牙裔/拉丁裔人群中，睡眠呼吸障碍和失眠与高血压和糖尿病发生之间的关联，共纳入11623名参与者，女性占52.6％，平均年龄41.1±14.9岁。存在睡眠呼吸障碍的人群，与没有睡眠呼吸障碍的人群比较，高血压发生的风险比1.54，糖尿病发生风险比1.37。失眠与高血压有关（风险比1.37），其中男性关联性更强。结论：睡眠呼吸障碍与高血压和糖尿病有关。失眠与高血压有关。这些结果支持将睡眠障碍作为预防和减少高血压、糖尿病的靶标。《SAVE研究：持续气道正压治疗对同时患有OSA和稳定性冠心病的患者的糖尿病的影响》Diabetes Care，2020年7月 (4)研究试图确定在同时患有稳定性冠心病和OSA患者中，长期持续气道正压（CPAP）通气治疗对血糖控制和糖尿病风险的影响。研究收集了888名同时患有稳定性冠心病和OSA患者，一组接受CPAP加常规治疗，另一组接受常规治疗，中位随访时间为4.3年。糖尿病的患者中，不同治疗组的血糖、糖化血红蛋白或降糖药物使用方面无显著差异。糖尿病前期、或新诊断的糖尿病患者中，组间也没有显著差异。有趣的是，女性糖尿病患者在常规治疗组表现较差，而接受CPAP治疗后病情更稳定。结论：在同时患有稳定性冠心病和OSA患者中，尚无证据证明长期CPAP治疗对血糖控制有益。但研究中发现的性别差异仍需进一步验证。阻塞性睡眠呼吸暂停的治疗一般治疗包括：减重、运动、侧卧位睡眠、避免酒精、避免使用精神类药物。主要治疗方法是气道正压治疗，常见模式包括持续气道正压（CPAP）、双水平气道正压（BPAP）和自动调定式的气道正压（APAP），最常用的是CPAP。替代治疗方法包括：轻中度患者可尝试口腔矫正器、存在上气道阻塞的患者可尝试上气道外科手术、也可尝试直接或间接刺激呼吸驱动的药物（如茶碱或乙酰唑胺）、或减少上气道塌陷的药物（如地昔帕明）。《对照研究：腭舌手术治疗中重度阻塞性睡眠呼吸暂停的患者》JAMA，2020年9月 (5)研究的目的是考察了腭舌手术对阻塞性睡眠呼吸暂停综合征（OSA）常规治疗失败患者的疗效。研究纳入常规治疗失败的、症状性的、中重度、阻塞性睡眠呼吸暂停患者101人，随机接受多次腭舌手术（改良悬雍垂腭咽成形术和微创舌体积缩小术）、或常规医疗（例如，改善睡眠姿势或减肥）。89%的患者完成了试验，手术组基线时的平均睡眠呼吸暂停低通气指数为47.9，6个月时为20.8；常规医疗组基线时为45.3，6个月时为34.5（6个月时，组间平均校正后差异为-17.6个事件/小时）。手术组基线时的Epworth嗜睡评分为12.4，6个月时为5.3；常规医疗组基线时为11.1，6个月时为10.5（6个月时，平均基线调整组间差异-6.7）。不良事件：手术组1例术后第5天发生心肌梗死，1例因吐血而住院观察。结论：常规治疗失败的、中重度阻塞性睡眠呼吸暂停症患者，接受悬雍垂腭咽成形术和微创舌体积缩小术，可减少呼吸暂停和低通气事件的发生，改善患者嗜睡症状。肺结核肺结核是结核分枝杆菌感染最常见的部位。（1）原发性肺结核主要发生于儿童期，也可以在青少年或成人中发生，其临床表现在人群中差异很大：低热70%、胸膜炎性胸痛25%、乏力咳嗽咽痛比较少见。X线表现：肺门淋巴结肿大65%，胸腔积液33%，肺部浸润27%。原发性感染后，90%的免疫系统正常者可以控制结核杆菌的进一步复制；随后结核杆菌可能进入潜伏期，10%的感染者进行性的出现肺结核肺炎。（2）复燃性肺结核的患者发热和盗汗更常见，约一半的患者有咳嗽、体重减轻、乏力。X线表现：上叶尖后段受累80-90%，空洞形成20%。《系统回顾和荟萃分析：近距离接触结核病人后，儿童罹患肺结核的风险》Lancet，2020年3月 (6)全球每年有数千万儿童接触结核分枝杆菌，但是，仍没有对受感染儿童罹患结核病的风险的估计，对接触调查和预防治疗的有效性也缺乏了解。在这篇系统回顾和荟萃分析中，纳入了来自34个国家的46个队列研究的数据。评估了137647例结核暴露儿童，对135512例儿童进行了429538人年随访，期间诊断出1299例流行性结核和999例散发性结核。结核感染阳性、但未接受预防治疗的儿童2年累计肺结核发病率明显高于结核感染阴性儿童。其中5岁以下儿童肺结核发病率最高，为19·0%。所有暴露儿童预防治疗的有效性为63%，对于结核感染阳性儿童预防治疗的有效性为91%。结论：结核暴露的婴儿和幼儿罹患结核病的风险非常高，大多数病例发生在接触者调查开始后的几周内。《前瞻性研究：接触耐多药结核病后异烟肼的防治效果》American Journal of Respiratory and Critical Care Medicine，2020年6月 (7)WHO建议单独使用异烟肼或异烟肼与利福平联合使用来治疗潜在的结核病感染。该研究的目的是研究单独使用异烟肼用于预防多药耐药结核感染的有效性。这个前瞻性群组研究纳入4500个肺结核病人和14044个结核暴露家庭，19岁以下的接触者共4216人，只有一半人接受了异烟肼预防治疗。异烟肼的预防作用十分显著，在接触非耐药结核病人时感染风险下降70%，在接触多药耐药结核病人后的感染风险下降81%。在接触异烟肼单药耐药结核病人时，异烟肼的预防作用稍弱（风险比0.80）。在第二项独立研究中，76名接受异烟肼预防的家庭接触者均未感染；而273名未接受异烟肼预防治疗的家庭接触者有8人感染，占3%。结论：即使接触多药耐药结核病患者，异烟肼也能有效降低接触者的结核发病率。《随机对照研究：补充维生素D预防结核杆菌感染》New England Journal of Medicine，2020年7月 (8)研究的目的是评估补充维生素D是否可以预防结核病感染。参与研究的8851名、结核分枝杆菌感染阴性的、维生素D缺乏的儿童，随机分入维生素D组或安慰剂组，干预持续3年。3年后，儿童的维生素D缺乏得到纠正，两组的平均25-羟-维生素D水平分别为31.0ng/mL和10.7ng/mL；但是两组间QuantiFERON-TB试验阳性比例没有差异，分别为3.6%和3.3%（P = 0.42）。维生素D组有21名儿童和安慰剂组有25名儿童被诊断患有结核病，分别有29人和34人因急性呼吸道感染住院治疗，发生率无显著差异。结论：维生素D缺乏的儿童中，补充维生素D没有降低结核感染的风险。肺结核的治疗无HIV感染的、成人的药物敏感性的、肺结核治疗：通常2个月强化治疗以及4-7个月维持治疗。强化阶段通常采用四联药物治疗 [ 包括异烟肼、利福霉素类（利福平、利福喷丁、利福布丁）、吡嗪酰胺、乙胺丁醇 ] ，维持治疗通常采用二联药物治疗（包括异烟肼、利福平）。耐药肺结核包括单药耐药和多药耐药。单药耐药的情况下，可选用其他的一线药物，也可联合氟喹诺酮类。多药耐药的治疗取决于药敏试验，原则是尽可能多的一线药物，再加上一种氟喹诺酮类（左氧氟沙星、莫西沙星）和/或另一种核心二线药物（如贝达喹啉、利奈唑胺）。药物研发进展：普托马尼（pretomanid，硝基咪唑嗪类抗菌药，2019年8月批准上市）。《随机研究：短疗程治疗利福平耐药的肺结核的3期临床研究》New England Journal of Medicine，2019年3月 (9)研究的目的是在对氟喹诺酮类和氨基糖苷类药物敏感的、利福平耐药的、结核患者中开展了一项3期非劣效性试验。共424例患者，随机分别接受含有大剂量莫⻄沙星的短疗程方案（9~11个月）或遵循2011年WHO指南推荐的⻓疗程方案（20个月）。132周后，⻓疗程方案组和短疗程方案中，分别有79.8%和78.8%的参与者报告了良好状态（P=0.02）。两组的严重不良事件发生率分别有45.4%和48.2%。短疗程方案组11.0%参与者和⻓疗程方案组6.4%参与者出现QT间期延⻓，并进行了药物调整。结论：在对氟喹诺酮类药物和氨基糖苷类药物敏感的、利福平耐药的结核患者中，包括大剂量莫西沙星的短疗程方案的主要疗效结局不劣于⻓疗程方案，安全性相似。支气管热成型术支气管热成形术（Bronchial Themoplasty）是一种治疗重度哮喘的手段，经由纤维光学支气管镜导入特质的导管，然后利用该导管对支气管壁施加热能，以削弱支气管平滑肌的收缩力、减轻气道平滑肌的增生。该操作通常需要在中度镇静下进行3次支气管镜下操作，每次间隔3周。主要针对的人群是治疗吸入性糖皮质激素和LABA控制不佳的、重症哮喘患者。但这项操作有风险，对其长期的疗效仍有一定的争议。《TASMA研究：支气管热成型术引起的气道平滑肌减少和对重症哮喘的治疗效果》American Journal of Respiratory and Critical Care Medicine，2020年7月(10)研究的目的是确定支气管热成型术对气道平滑肌的质量的影响，并确定哪一类重症哮喘患者适合接受此项治疗。研究纳入40例重症哮喘患者，随机分为即时支气管热成型术组和延迟支气管热成型术组。即时手术组的中位气道平滑肌质量减少>50%，而延迟组的气管平滑肌的质量无变化（p=0.0004）。即时手术组和延迟手术组中，哮喘控制问卷评分分别降低了0.79和升高了0.09（p=0.006）；哮喘生活质量问卷评分分别升高了0.83和降低了0.02（p=0.04）。治疗反应（n=35）与血清IgE和嗜酸性粒细胞呈正相关，但与气道平滑肌基线质量无关。结论：支气管热成型术后气道平滑肌的质量明显降低。疗效与血清IgE和嗜酸性粒细胞水平相关，而与气道平滑肌的质量无关。《随机对照临床研究：129Xe-MRI引导的一次支气管热成形术》American Journal of Respiratory and Critical Care Medicine，2020年8月 (11)不良事件限制了支气管热成形术在重症哮喘中的应用，该研究的目的是使用氙129磁共振技术（129Xe-MRI）引导下进行支气管热成形术。研究对30例严重哮喘患者进行容积CT和129Xe-MRI，以定量节段性通气缺损，然后被随机分组至磁共振引导组（行一次支气管热成形术治疗6个病变最严重的支气管）、或非引导组（标准的三阶段支气管热成形术）。治疗12周后，磁共振引导组与非引导组相比，生活质量评分改善无显著差异（P = 0.201），但肺通气不良和肺不通气的比例下降更显著（-17.2%；P = 0.009）。磁共振引导组中33%的患者术后哮喘加重；非引导组有73%的患者哮喘加重（P = 0.028）。结论：与标准的三次支气管热成形术相比，磁共振引导下的一次支气管热成形术可以取得类似的短期改善，且围手术期不良事件较少。CT诊断人工智能系统《应用人工智能系统对新型冠状病毒肺炎进行CT诊断、定量和预后评估》 Cell，2020年6月 (12)许多罹患COVID-19的患者发展为肺炎，并迅速发展为呼吸衰竭。然而，快速诊断与鉴别高危患者、并早期干预仍十分具有挑战性。使用大型CT数据库分析4154名患者的资料后，研究人员开发了用以诊断和鉴别诊断新型冠状病毒肺炎的人工智能系统。此人工智能系统能够客观、定量的识别和测量新型冠状病毒肺炎病变CT上的肺部损害指标，如小结节、毛玻璃影、实变影，评价疾病严重程度，也可用于客观、定量的评价药物有效性。结合患者临床指标，如吸氧频率、血氧饱和度、血气分析、肝功能、凝血功能等，可以综合分析并预测患者发展为危重症的可能性和时间。参考文献1.Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-39.2.Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim S-W, Carcereny Costa E, et al. Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2019;381(21):2020-31.3.Li X, Sotres-Alvarez D, Gallo LC, Ramos AR, Aviles-Santa L, Perreira KM, et al. Associations of Sleep Disordered Breathing and Insomnia with Incident Hypertension and Diabetes: The Hispanic Community Health Study/Study of Latinos. Am J Respir Crit Care Med. 2020.4.Loffler KA, Heeley E, Freed R, Meng R, Bittencourt LR, Gonzaga Carvalho CC, et al. Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease. Diabetes Care. 2020;43(8):1859-67.5.MacKay S, Carney AS, Catcheside PG, Chai-Coetzer CL, Chia M, Cistulli PA, et al. Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial. JAMA. 2020.6.Martinez L, Cords O, Horsburgh CR, Andrews JR. The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis. Lancet. 2020;395(10228):973-84.7.Ganmaa D, Uyanga B, Zhou X, Gantsetseg G, Delgerekh B, Enkhmaa D, et al. Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease. N Engl J Med. 2020;383(4):359-68.8.Nunn AJ, Phillips PPJ, Meredith SK, Chiang C-Y, Conradie F, Dalai D, et al. A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. New England Journal of Medicine. 2019;380(13):1201-13.9.Huang CC, Becerra MC, Calderon R, Contreras C, Galea J, Grandjean L, et al. Isoniazid Preventive Therapy in Contacts of Multidrug-resistant Tuberculosis. Am J Respir Crit Care Med. 2020.10.Goorsenberg AWM, d'Hooghe JNS, Srikanthan K, Ten Hacken NHT, Weersink EJM, Roelofs J, et al. Bronchial Thermoplasty Induced Airway Smooth Muscle Reduction and Clinical Response in Severe Asthma: The TASMA Randomized Trial. Am J Respir Crit Care Med. 2020.11.Hall CS, Quirk JD, Goss CW, Lew D, Kozlowski J, Thomen RP, et al. Single-Session Bronchial Thermoplasty Guided by (129)Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2020;202(4):524-34.12.Zhang K, Liu X, Shen J, Li Z, Sang Y, Wu X, et al. Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography. Cell. 2020;181(6):1423-33 e11.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.275321v1?rss=1 Authors: Goldfarb, D., Bahrenberg, T., Yardeni, E. H., Feintuch, A., Bibi, E. Abstract: MdfA, a member of the major facilitator superfamily (MFS), is a multidrug/proton antiporter from E. coli that has been considered a model for secondary multidrug (Mdr) transporters. Its transport mechanism, driven by a proton gradient, is associated with conformational changes, which accompany the recruitment of drugs and their release. In this work, we applied double-electron electron resonance (DEER) spectroscopy to locate the binding site of one of its substrates, tetraphenylphosphonium (TPP) within available crystal structures. We carried out Gd(III)-nitroxide distance measurements between MdfA labeled with a Gd(III) tag and the TPP analog mito-TEMPO (bearing the nitroxide moiety). Data were obtained both for MdfA solubilized in detergent micelles (n-dodecyl-{beta}-D-maltopyranoside )DDM)), and reconstituted into lipid nanodiscs (ND). For both DDM and ND, the average position of the substrate at a neutral pH was found to be close to the ligand position in the If (inward facing) crystal structure, with the DDM environment exhibiting a somewhat better agreement than the ND environment. We therefore conclude that the If structure provides a good description for substrate-bound MdfA in DDM solution, while in ND the structure is slightly modified. A second binding site was found for the ND sample situated at the cytoplasmic side, towards the end of transmembrane helix 7 (TM7). In addition, we used DEER distance measurements on Gd(III) doubly labeled MdfA to track conformational changes within the periplasmic and cytoplasmic sides associated with substrate binding. We detected significant differences in the periplasmic side of MdfA, with the ND featuring a more closed conformation than in DDM, in agreement with earlier reports. The addition of TPP led to a noticeable conformational change in the periplasmic face in ND, attributed to a movement of TM10. This change was not observed in DDM. Copy rights belong to original authors. Visit the link for more info
Dr. Don and Professor Ben talk about the microbiological risks from puppies. Dr. Don - not risky
Bacteriophages have long been used to treat infections. These naturally occurring virus are capable of killing bacteria, but each strain of phage is highly specific. Because of their unique mechanism of action, they provide a potential to address the growing threat posed by multidrug-resistant bacteria, but to treat someone, the right phage must be matched to each patient's infection. Adaptive Phage Therapeutics believes it's found a way to create phage therapies suited to treat patients with drug-resistant infections by building a bank of targeted and genomically-screened bacteriophage and testing individual patient's bacterial colony against that to determine the appropriate phage to treat them. We spoke to Greg Merril, co-founder and CEO of Adaptive Phage Therapeutics, about the origins of the company, how its technology works, and the regulatory hurdles for producing customized therapies to treat individual patients.
In response to the COVID-19 pandemic, medical device companies are improving and saving lives through innovative technologies and methods to combat the virus. In this episode of the Global Medical Device Podcast, Jon Speer talks to Jeff Veenhuis and Quinn Leach from Surfacide, a company actively working in the fight against COVID-19 with their proven UV-C technology that destroys pathogens, including the novel coronavirus. Listen to their powerful story about how Surfacide has embraced the opportunity and is scaling operations in order to protect frontline healthcare workers around the world. Some of the highlights of the show include: - ABCs of UV: All three ultraviolet heat types come from the sun, only UV-C is blocked by the ozone layer because high doses can damage genetic material and break protein bonds. - Multidrug-resistant organisms, such as COVID-19, MRSA, and SARS, affect 5-15 percent of hospital patients and create inefficiency, additional cost, and immortality. - Coronavirus Data and Evidence: Until a specific energy type is determined, early stages of Surfacide’s UV-C research airs on the side of caution and compliance. - Personal Protective Equipment (PPE): How can UV-C be used to disinfect masks and do a limited number of reprocessings? - Greenlight Guru’s Quality Management System (QMS) offers scalability for Surfacide’s solutions and sales to expand globally for a sustainable business. - Surfacide’s goal is to provide a safe environment for healthcare workers and patients by eliminating the bioburden potential. - Prevention Strategies and Infection Control Standards: Continue to wear masks, gloves, and other PPE at home, work, and everywhere else to make a difference and the world safer.
Dr. Bachmeier presents an up-to-date review of newer-generation antimicrobials designed to be effective against infections with multiple drug-resistant pathogens. He first reviews the different types of extended-spectrum beta-lactamase (ESBL) resistance. He then discusses the significance of Carbapenemase-producing enterobacteriaceae and ESBL producing E coli, Klebsiella pneumonia, and Pseudomonas aeruginosa strains. Such organisms have become increased threats to our patients over the last two decades while new drug approvals have dwindled. Dr. Bachmeier reviews Ceftolozane-tazobactam, Ceftazidime-avibactam and their current indications. He then reviews Meropenem-vaborbactam and its utility in the treatment of Klebsiella pneumonia carbabenemase (KPC) infections. He then discusses imipenem-relebactam and its advantages in the treatment of MDR gram-negative infections. Lastly, he reviews plazomycin, eravacycline, and Cefiderocol.
This episode features two legends of biomedical research. In the realm of human health and longevity, cancer’s ability to mutate, grow, and thwart the body’s natural defenses presents one of the greatest scientific challenges of our time. In 2001, Dr. Ira Pastan led the creation of a new type of cancer drug, a recombinant immunotoxin, that promised to directly target and kill cancer cells. After years of research and clinical trials, this first-generation immunotoxin was approved by the FDA in September 2018 for certain adults with hairy cell leukemia, providing a promising new therapy to a group of patients who previously had few other options. And we have a special guest host for this episode, Dr. Michael Gottesman, who, as the NIH Deputy Director for Intramural Research, leads the thousands of researchers and clinicians working within the IRP each day — while also conducting groundbreaking research in his own laboratory into how cancer cells become resistant to chemotherapy and other anti-cancer drugs. Drs. Gottesman and Pastan are two guiding lights in our quest to overcome the obstacles to effectively treating cancer in order to improve and save potentially millions of lives. As friends and colleagues for many years, they also trained and collaborated with several of the most celebrated IRP researchers who made extraordinary breakthroughs for human health.
Dr Tom Crellen from MORU (Mahidol Oxford Research Unit) in Bangkok, Thailand, tells us about his research on transmission dynamics of infections aquired in hospitals. Multidrug resistant bacteria are a major problem in Southeast Asia, particularly for infections acquired in hospitals. Patients data and bacteria sequence allow the reconstruction of transmission networks. Using these date, we can also build simulations to investigate the impact of possible interventions, which then inform future clinical trials.
Multidrug resistant lung infections present an increasingly common and increasingly dangerous threat to all individuals with cystic fibrosis. Common CF pathogens — Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Stenotrophomonas maltophilia — are all showing increasing resistance to clinicians' usual antibiotic armamentarium.In this issue, Dr. Claire Elson, from the University of Missouri Kansas City School of Pharmacy, and Dr. Christopher Oermann, from the UMKC School of Medicine, describe strategies for the clinical management of these resistant infections.Take our post-test to claim CME credits.To read a companion newsletter click here. Hosted on Acast. See acast.com/privacy for more information.
En el program de esta semana hablamos sobre Pseudomonas aeruginosa y el rol en el tratamiento que tendría el ceftolozano / tazobactam sobre todo el lo referente a cepas multiresistentes y como los diversos mecanismos de resistencia que este tipo de bacterial puede manifestar pueden afectar la sensibilidad a dicho antimicrobiano. Referencias: A.P Magiorakos y colaboradores. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18 (3) 268-81. Gabriel Cabot y colaboradores. Pseudomonas aeruginosa Ceftolozane-Tazobactam Resistance Development Requires Multiple Mutations Leading to Overexpression and Structural Modification of AmpC. Antimicrob Agent Chemother 2014; June 58 (6): 3091-9. Pablo A. Fraile-Ribot y colaboradores. Mechanisms leading to in vivo ceftolozane/tazobactam resistance development during the treatment of infections caused by MDR Pseudomonas aeruginosa. J Antimicrob Chemother 2017; 73: 658-663. Yu Mi Wi y colaboradores. Activity of Ceftolozane-Tazobactam against Carbapenem- Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms. Antimicrob Agents Chemother 2017; 62 (1). Andrew Walkty y colaboradores. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Canada as part of the CANWARD study, 2008–16. J Antimicrob Chemother 2018; 73: 703-708. Tommaso Giani y colaboradores. Italian nationwide survey on Pseudomonas aeruginosa from invasive infections: activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of carbapenemase producers. J Antimicrob Chemother 2018; 73: 664-671. David M. Livermore y colaboradores. Activity of ceftazidime/avibactam against problem Enterobacteriaceae and Pseudomonas aeruginosa in the UK, 2015–16. J Antimicrob Chemother 2018. 73: 648-657. La Frase de la Semana: Y esta semana no puede ser sino de Stephen Hawkings debido a queel británico murió este martes (la madrugada del miércoles en Inglaterra), a sus 76 años. Fue uno de los físicos más importantes de la cosmología moderna y se destacó por su teoría sobre agujeros negros y por sus esfuerzos matemáticos para unificar la teoría general de la relatividad de Einstein con los conocimientos emergentes de la física cuántica. La frase dice: “El peor enemigo del conocimiento no es la ignorancia, es la ilusión del conocimiento”
In this interview, Dr. Jennie Johnstone tells us about a strain of gram-negative bacteria called carbapenemase-producing Enterobacteriaceae (CPE) that is resistant to most antibiotics. She also discusses what the public and the health care system can do to help prevent the spread of drug-resistant organisms. Dr. Johnstone is infection prevention and control physician-scientist at Public Health Ontario and infectious disease specialist for St. Joseph’s Health Centre in Toronto. She co-authored a practice article in the CMAJ titled "Five things to know about...Emerging multidrug-resistant bacteria." Full practice article (subscription required): www.cmaj.ca/lookup/doi/10.1503/cmaj.170110 ----------------------------------- Subscribe to CMAJ Podcasts on iTunes, Stitcher, Overcast, Instacast, or your favourite aggregator. You can also follow us directly on our SoundCloud page. Our podcasts are also released on www.cmaj.ca and on www.cmajblogs.com.
Dr Lorenz von Seidlein from our MORU unit in Bangkok, Thailand, tells us about his research on malaria elimination in the Greater Mekong sub-region Multidrug resistant P. falciparum malaria is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for artemisinin combination therapies, the main falciparum malaria medicines. A further spread from Myanmar to India then sub-Saharan Africa would be a global public health disaster. TME seeks the best ways to eliminate drug-resistant malaria, using both technical solutions and novel ways that engage entire communities. Dr Lorenz von Seidlein coordinates MORU's Targeted Malaria Elimination (TME) study, which seeks to eliminate artemisinin resistant falciparum malaria by treating entire communities that have significant levels of subclinical malaria parasite infections and transmission with the antimalarial Dihydroartemisinin-piperaquine (DHA-PIP).
Dr Lorenz von Seidlein from our MORU unit in Bangkok, Thailand, tells us about his research on malaria elimination in the Greater Mekong sub-region Multidrug resistant P. falciparum malaria is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for artemisinin combination therapies, the main falciparum malaria medicines. A further spread from Myanmar to India then sub-Saharan Africa would be a global public health disaster. TME seeks the best ways to eliminate drug-resistant malaria, using both technical solutions and novel ways that engage entire communities. Dr Lorenz von Seidlein coordinates MORU’s Targeted Malaria Elimination (TME) study, which seeks to eliminate artemisinin resistant falciparum malaria by treating entire communities that have significant levels of subclinical malaria parasite infections and transmission with the antimalarial Dihydroartemisinin-piperaquine (DHA-PIP).
Margaret Parker, MD, MCCM, speaks with Marin H. Kollef, MD, about the article, Impact of Sepsis Classification and Multidrug-Resistance Status on Outcome Among Patients Treated With Appropriate Therapy, published in Critical Care Medicine.
Margaret Parker, MD, MCCM, speaks with Marin H. Kollef, MD, about the article, Impact of Sepsis Classification and Multidrug-Resistance Status on Outcome Among Patients Treated With Appropriate Therapy, published in Critical Care Medicine.
Running Time : 5minutes Overview: The most effective means available against bacterial infectious diseases is the administration of antibacterial drugs that kill or inactivate the bacteria. When so many of these drugs are overprescribed, however, bacteria that have developed a resistance to a number of such drugs will likely emerge. Just how widespread are these multidrug-resistant bacteria? And will medical researchers be able to produce new drugs that can control them? (Japanese edition has been published in Jul 31, 2014) Cast: Taro Urase(Professor, School of Bioscience and Biotechnology, Tokyo University of Technology), Yasumitsu Sakamoto(Assistant Professor, School of Pharmacy, Iwate Medical University) JST Science News 2014(EnglishVer.) http://sciencechannel.jst.go.jp/Q140001/ JST Science News 2014(JapaneseVer.) http://sciencechannel.jst.go.jp/M140001/ JST Science Channel(Non-Japanese Programs) http://sciencechannel.jst.go.jp/non_japanese.html (c)Japan Science and Technology Agency
Read the full story with photos at: https://www.otsuka.co.jp/en/company/globalnews/2015/0116_02.html Otsuka’s commitment to fight TB Infectious disease experts from around the world gathered in Okinawa, Japan in mid-January for the second Nikkei Asian Infectious Diseases conference. Otsuka signaled its ongoing commitment to the fight against TB by again co-sponsoring the conference. Game changers Asia, which accounts for more than two-thirds of the world’s TB burden, clearly must be at the center of the goal to defeat TB globally. The introduction of a new drug for multidrug-resistant TB, as well as1new technologies to diagnose TB and its drug-resistant strains, are perceived as potential “game changers” in the fight against TB in the region. However, one prominent specialist present noted that a badly designed MDR-TB program may actually cause more harm than having no program at all, citing the need for high-quality drug sensitivity testing and precise follow-up with patients. This mixture of new optimism and renewed concern about TB prompted the event organizers to select TB as a key theme of the conference. TB drug development needs to be simpler Hiroshi Ishikawa, Ph.D. (right) Fellow, Medicinal Chemistry at Otsuka, who was one of the key members of the Otsuka team that developed the drug delamanid, spoke with stirring passion at the conference about the scale of the challenge involved in creating a new TB drug. It included the study of over 14,000 compounds across two decades, something that a single chemist could not hope to accomplish in 100 years. With an eye toward the future he noted that TB drug development will need to be simpler to reduce costs and facilitate broader access by patients. Dr. Ishikawa also drew the attention of the audience to broader issues in the fight against TB. One is the need for improved diagnostics, especially kits that can rapidly measure TB bacilli susceptibility to drugs and biomarkers that can differentiate active from latent cases. Max Yoshitake (left), Leader, Global TB Team was called on by one of the session moderators for his insights on issues such as latent TB, which is present in over 30% of the world’s population. Mr. Yoshitake noted that one important challenge for Otsuka and others will be to shorten the duration of treatment to just a couple of months. Overall, a sense of cautious optimism filled the conference room. This was suggested by the nearly 45% decline in the TB mortality from 1990 to 2013, partly due to the DOTS (Directly Observed Treat Short Course) and Stop TB strategies. Looking forward, new diagnostics and drugs to treat the most difficult forms of the disease also hold promise. But no one was ready to say that the victory over TB, a disease as old as humanity itself, is near at hand.
Host: Matt Birnholz, MD Tuberculosis is an ancient disease that remains an important global cause of morbidity and mortality. In most cases, TB can be treated and cured by taking a combination of several drugs for 6 to 12 months. When inappropriate or incomplete treatment takes place, however, TB bacteria can develop multidrug resistance (MDR). Annually, there are approximately 500,000 cases of MDR TB, and 150,000 deaths. Although there are simple rapid tests that have improved the diagnosis of the disease, there is immense potential to increase the number of persons diagnosed with MDR TB, and to do so more quickly to initiate treatment sooner. This session of CDC′s Public Health Grand Rounds will explore how more patients can benefit from advances in diagnostic and treatment options, resulting in an overall reduction in morbidity from MDR TB. The role of CDC, WHO and other partners in combating this public health epidemic will also be discussed. To view the complete video recording of this and other CDC Public Health Grand Rounds sessions, visit http://www.cdc.gov/about/grand-rounds/
Read the full story with photos at: https://www.otsuka.co.jp/en/company/globalnews/2014/0214_01.html The Nikkei Asian Infectious Diseases Conference was held on February 14 and 15, 2014 in Nago City, Okinawa in order to discuss measures for preventing the spread of communicable diseases in Asia. The Okinawa prefectural government and the Ministry of Health, Labour and Welfare provided support for the conference, and Otsuka Pharmaceutical participated as a cosponsor. Otsuka presented the panel discussion on tuberculosis, which was one of the important panel discussions at the conference. About the tuberculosis panel discussion: Tuberculosis is one of the three leading communicable diseases in the world, along with malaria and AIDS. Tuberculosis is said to infect one-third of the world’s population of 7 billion. Tuberculosis is a problem of the present, not the past, and not only is it a problem in developed countries, it is an even more serious problem in Asia and in developing countries. The discussion covered recent advances that have been made by Otsuka Pharmaceutical in response to the demand for new drugs, and what steps are needed to combat tuberculosis in the future. “Overcoming Multidrug-Resistant Tuberculosis Through Innovation” Dr. Hiroshi Ishikawa, Fellow, Otsuka Pharmaceutical The reason there have been no new tuberculosis drugs in 50 years is that Mycobacterium tuberculosis is a tough organism, and development is difficult and requires a tremendous amount of time and money. Why did Otsuka Pharmaceutical want to take on such a challenge? One reason is that for more than 40 years Otsuka Pharmaceutical’s corporate philosophy has been to improve the health of people around the world. A second reason is related to Otsuka’s global presence – Otsuka opened a plant in Thailand in 1973 and one in China in 1980, and now has approximately 30,000 employees around the world, 70% of whom are employed overseas. And 70% of these overseas workers are in Asia, and are therefore living, with their families, in high-burden tuberculosis countries. A third reason is that, since opening a research institute in 1971, Otsuka’s stated research mission has been to not conduct any imitative research, but to conduct research that is unique to Otsuka, research that, in fact, only Otsuka is capable of conducting, in order to discover first-in-class drugs. Moreover, Otsuka was able to forcefully pursue tuberculosis research because it was the idea of Akihiko Otsuka, Otsuka Pharmaceutical’s current Chairman. Research began in 1982 but efficacy was not met and the research failed. Because tuberculosis is a tough organism that grows slowly over 24 hours, Otsuka instead adopted an approach that involved searching for a drug that was not only potent, but also toxic, and then trying to ameliorate the toxicity later. This is the exact opposite of the conventional approach. Together with partner laboratories, Otsuka synthesized 14,000 types of compounds and, in 2002, discovered a promising novel compound; clinical studies were initiated in 2004. As a future research activity, Otsuka would like to try to establish a global regimen that includes new tuberculosis drugs in order to prevent the emergence of strains that are resistant to new drugs. Dr. Ishikawa said that Otsuka’s aim is to discover an anti-tuberculosis drug that can be used to treat latent tuberculosis infections and that can cure tuberculosis quickly, in 1 to 2 months, in order to prevent the emergence of multidrug-resistant strains. “Controlling TB and MDR-TB in Asia, and the Role of Japan” Dr. Tadao Shimao, Advisor, Japan Anti-Tuberculosis Association The emergence of multidrug-resistant tuberculosis and HIV/AIDS and the movement of people from developing to developed countries (the moving of tuberculosis/communicable diseases) are major problems in Asia and Japan. Around the globe, 940,000 people die of tuberculosis, approximately 70% of them in Asia, and multidrug-resistant tuberculosis accounts for 187,000 deaths. Dr. Shimao said that Japan’s role should be to develop simple techniques that allow multidrug-resistant strains to be detected and new drugs to follow in the footsteps of Otsuka Pharmaceutical’s new anti-tuberculosis drug. “Forgotten But Far From Gone” Professor Lee Reichman, Executive Director, New Jersey Medical School Global Tuberculosis Institute Every year, there are 450,000 cases of multidrug-resistant tuberculosis. Pandemic regions are Southeast Asia, which accounts for 40%, Africa, which accounts for 26%, and the Central and South America, which accounts for 19%. Overlapping infection with HIV or the presence of a multidrug-resistant strain results in a cure rate of no more than approximately 50%. In the absence of a cure, the death rate is 90%. New drugs that can effect a rapid cure and new drugs that can be used to treat multidrug-resistant tuberculosis and that have little hepatotoxicity and few drug interactions are needed. Even though tuberculosis is the world’s tenth most lethal disease, only 5 to 8 products are currently in development. Tuberculosis is a disease that must not be forgotten, as it is far from gone. About the Nikkei Asian Infectious Diseases Conference The conference was attended by researchers and governmental representatives from all over Asia, including Thailand, Vietnam, and Indonesia; there were 30 presenters, and 150 participants in all, from both Japan and abroad. Japan is closely connected to other countries in Asia through a web of economic, personal and other ties. Communicable diseases pose the biggest danger to health in Asia, and Japan needs to play a leading role in combating them. The official statement of the conference asserted the need for the creation of an Asian network for fighting communicable diseases.
Guest: Shelly Batra, MD Host: Maurice Pickard, MD Multidrug Resistant (MDR) Tuberculosis is a growing public health epidemic in India. Experts estimate there could easily be over 5 million cases of MDR TB at present, with each untreated patient capable of spreading the disease to 10-15 others per year. The non-profit organization Operation ASHA has expanded its role considerably over the past few years to stem this tide of TB transmission from the poorest to the most prosperous communities, bringing innovative treatment protocols right to the patients' doorsteps. Dr. Shelly Batra, president of Operation ASHA, discusses the progress being made in this increasingly global public health campaign. Hosted by Dr. Maurice Pickard.
Multidrug-resistant Gram-negative induced sepsis poses an increasing threat to the vulnerable intensive care patient. The study by Toufekoula and colleagues reports the serum and tissue concentration of malondialdehyde (MDA), the toxic end product of lipid peroxidation, during the course of experimental and human Gram-negative sepsis. The complementary results from this dual experimental and clinical approach argue for highly compartmentalized lipid peroxidation during sepsis. Establishing a correlation between MDA concentration and survival provides valuable insights into the pathophysiology of Gram-egative sepsis. Yet, further studies are needed to understand and establish MDA as a biomarker during sepsis aggravated by organ failure.
Superbugs! is the media's term for multidrug resistant bacteria. These bugs were often caught from surgical wounds but now anyone can catch them and in 33% of cases these are fatal. Ben Long discusses this in Deakin 3-minute Thesis July 2011
Vortragsreihe des TR 3
In this episode, Multidrug-resistant tuberculosis (MDR-TB) has been recorded at the highest rate ever; and WHO and its partners ship vaccines to Paraguay in response to the yellow fever outbreak.
Multidrug resistant MRSA infection in men who have sex with men; an interview with study coauthors Binh Diep, PhD and Henry Chambers, MD, of the University of California San Francisco; and a systematic review of evidence for improving end-of-life care. Plus a summary of all the articles in this week's issue.
An HIV/AIDS activist since his diagnosis more than 20 years ago, Nelson Vergel is also an advocate for regular exercise and good nutrition. After all these years, Nelson remains dedicated to helping people with HIV. He runs a few Web sites and discussion groups. He also has a full schedule of talks around the country. Originally from Venezuela, he has been living in Houston, Texas, almost as long as he's known he's HIV positive. Among Nelson Vergel's top tips for surviving HIV/AIDS: Stay informed and connect with others.
In gene therapy, a clinically relevant therapeutic effect requires long-term expression of the desired gene at a level sufficient to correct or at least alleviate the underlying gene defect. One approach to achieve persistent as well as high-level transgene expression in a significant percentage of target cells would be to select cells expressing both the desired transgene and a linked selectable gene such as the human multi-drug resistance (MDR1) gene-in a bicistronic vector. Because of its accessibility, the skin is a very attractive target tissue to select genetically modified cells, allowing topical application of a selecting agent, thus minimizing potential toxic side effects. Among the potential selecting drugs, agents that block cell division, such as colchicine, are of particular interest because the use of anti-mitotic drugs takes advantage of the rapid keratinocyte ( KC) turnover in the epidermis and the need for continued proliferation to substitute the KC lost due to selection. Before assessing the therapeutic benefit of such an approach, several key questions need to be answered in preclinical models: ( 1) Does topical colchicine application achieve the desired in vivo effect by blocking KC mitosis without eliciting unwanted toxic side effects? ( 2) Are MDR-transduced (MDR+) human KC still able to proliferate and differentiate when treated with colchicine? ( 3) Can MDR+ KC be enriched by topical selection? ( 4) Does topical selection result in persistent transgene expression by selecting KC stem cells expressing MDR? To answer these questions and to test the feasibility of such an approach both an in vitro skin equivalent and an in vivo human skin graft model were developed in which MDR+ KC were treated with different dosages of colchicine. Quantitative and qualitative analyses of MDR expression in human KC showed that topical colchicine treatment selects high-level transgene expression in a high percentage of KC. Moreover, determination of transgene copy numbers demonstrated that MDR+ KC progenitor cells were enriched by topical selection resulting in long-term expression of the transgene in the skin. Thus, in summary, these models demonstrate that topical selection of MDR+ KC is a safe approach to efficiently enhance long-term gene expression in the skin and holds future promise for clinical gene therapy applications. Copyright (C) 2004 S. Karger AG, Basel.
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