The last episode of the year carries a special end-of-year message from the CMI Comms editors and replays the very first episode of Communicable aired on 10 May 2024, in which editors Angela Huttner, Marc Bonten, and Erin McCreary discuss late-breaker clinical trials presented at ESCMID Global 2024 in Barcelona, providing insights into the trials’ designs, results, and implications. The DOTS trial compared two doses of long-acting dalbavancin to standard of care in patients with complicated S. aureus bacteraemia. GAME-CHANGER compared cefiderocol to standard of care for Gram-negative infections. PediCAP compared oral step-down therapy with amoxicillin with or without clavulanic acid at shorter durations to the current WHO-recommended standard of five days of intravenous antibiotic therapy in children with severe pneumonia. Additional results from the MULTICAP and CLEEN trials, the CAMERA-2 follow-on in vitro analysis, and the Burkina Faso Escherichia coli transmission study are also discussed. This episode was peer-reviewed by Dr. Yousra Kherabi (Clinical Trials Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA; Infectious and Tropical Diseases Department, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris; and Université Paris Cité, Inserm, IAME, Paris, France).

The topic of climate change can engender a ‘doom and gloom’ narrative, as many climate and health consequences are already manifesting. Our host, Dr. Navaneeth Narayanan is joined by two ID physicians passionate about climate change and sustainable clinical practice, Dr. Shreya Doshi (Washington DC, US) and Dr. Laura Jung (Leipzig, Germany). Together they discuss new trends in infectious diseases observed in clinical practice as a direct consequence of climate change, including how tropical diseases are not so tropical anymore. They also outline ways individual clinicians and hospitals can be more sustainable and offer additional resources for the listeners (see below).  

This episode was edited by Kathryn Hostettler and peer reviewed by Dr. Loora Grünvald of the University of Tartu, Estonia. 

Literature

• Mora C et al. Nat Clim Chang (2022). doi: 10.1038/s41558-022-01426-1
• Doshi S et al. J Pediatric Infect Dis Soc (2023). doi: 10.1093/jpids/piae029
• Hofmeister RJ et al. OFID (2024). doi: 10.1093/ofid/ofae368 
• Judson SD et al. OFID (2024). doi: 10.1093/ofid/ofae691
• Jung L et al. Lancet Planet Health (2023). 10.1016/S2542-5196(22)00253-4
• UN General Assembly High-Level Meeting on antimicrobial resistance 2024 https://www.who.int/news-room/events/detail/2024/09/26/default-calendar/un-general-assembly-high-level-meeting-on-antimicrobial-resistance-2024 

 Additional resources

• Lancet countdown on health and climate change  https://www.thelancet.com/countdown-health-climate
• Medicine for a changing planet https://www.medicineforachangingplanet.org/
• Rx for climate https://www.rxforclimate.org/

Wastewater surveillance is a powerful epidemiological tool that “mirrors our life,” and has gained wide attention in recent years due to its application during the COVID-19 pandemic. The hosts this week, Drs. Navaneeth Narayanan and Emily McDonald, are joined by two wastewater surveillance experts, Dr. Nasreen Hassoun-Kheir of Geneva University Hospitals, a WHO Collaborating Centre on antimicrobial resistance (AMR), as well as Professor David Graham of Newcastle University, United Kingdom, to discuss how this surveillance method—as well as a multidisciplinary approach—are central to understanding community health, infection control and pandemic preparedness.

This episode was edited by Kathryn Hostettler and peer reviewed by Dr. James Donnelly of the Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.

Literature

UN Environment Programme (UNEP), Bracing for superbugs (2023) https://www.unep.org/resources/superbugs/environmental-action 

Hassoun-Kheir N, et al. EMBRACE-WATERS statement (2021). doi:10.1016/j.onehlt.2021.100339

Hassoun-Kheir N, et al. Systematic review (2020). doi: 10.1016/j.scitotenv.2020.140804

Trask JD, et al. (1942). https://pmc.ncbi.nlm.nih.gov/articles/PMC2135222/

Chapters

• (00:00) - Introduction

Substandard and falsified (SF) antimicrobials are a neglected global health problem and have been implicated as drivers of antimicrobial resistance (AMR). Substandard medicines are authorized medical products that fail to meet either their quality standards or their specifications, whereas falsified medicines are those that deliberately and fraudulently misrepresent their identity, composition or source. Host Angela Huttner is joined by Pernette Bourdillon Esteve, Technical Officer for the World Health Organization’s Substandard/falsified Medical Products group, and Ben Cooper, epidemiologist at Oxford University and head of its Drug-Resistant Infection and Disease Dynamics (DRIaDD), to explore the effects of SF antimicrobials on people and AMR.

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Arjana Zerja of Mother Teresa University Hospital in Tirana, Albania.

Literature

Cavany S et al.  Nat Commun 14, 6153 (2023). doi: 10.1038/s41467-023-41542-w

WHO Global Surveillance and Monitoring System for substandard and falsified medical products (2017). https://www.who.int/publications/i/item/9789241513425 

The market of predatory publishing is as lucrative as it is unethical. Predatory journals are disguised as legitimate entities, and prey on both early-career academics and the naïve. In this episode of Communicable, hosts Angela Huttner and Marc Bonten are joined by Editors-in-chief Ursula Hofer (Lancet Infect Dis) and Leonard Leibovici (CMI) to discuss the various schemes of the ‘Wild West’ of publishing, and how to avoid them. 

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Özlem Türkmen Recen, Izmir Public Health Laboratory, Izmir, Türkiye.

Literature 

Research4Life https://www.research4life.org/ 

Benedictus R et al. Nature 2016 https://www.nature.com/articles/538453a

Enterococci are commensal microbes, part of the healthy microflora populating the human gut. But they are also opportunistic pathogens and notorious nosocomial agents with intrinsic traits that promote their pathogenesis and make them difficult to kill. In the third instalment of the Nightmare Series, hosts Angela Huttner and Thomas Tängdén are joined by enterococcal experts Kimberly Kline (University of Geneva) and Louis Rice (Brown University) to discuss what make vancomycin-resistant enterococci, or VRE, such a clinical nightmare. Enterococcus faecalis and Enterococcus faecium are the focus.

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Nunzia Esposito of the University of Naples Federico II, Naples, Italy.

Literature 

Stellfox ME et al. J Antimicrob Chemother 14 Feb 2024. doi: 10.1128/mbio.03396-23 

Rogers R & Rice LB. Clin Infect Dis 15 Jan 2024. doi: 10.1093/cid/ciad613

Lebreton F et al. Cell 18 May 2017. doi: 10.1016/j.cell.2017.04.027

Donskey CJ et al. N Engl J Med 28 Dec 2000. doi: 10.1056/NEJM200012283432604

Carbapenemase producers are a nightmare for clinicians. Not only are they resistant to carbapenems, a last resort β-lactam antibiotic, they are notorious for developing multidrug and pandrug resistances resulting in limited to no treatment options.  In this episode of Communicable, hosts Angela Huttner and Thomas Tängdén sit down with Dr. David Paterson (National University of Singapore) and Dr. Souha Kanj (American University of Beirut Medical Center, Lebanon), two ID physicians from regions where carbapenem-resistant Enterobacteriaceae or CRE, and carbapenem-resistant Acinetobacter are widespread.  The episode begins with the history and emergence of CRE and reviews current epidemiology, diagnosis (including the Ambler classification of β-lactamases) and treatment options. Lessons and insights from personal experiences are shared to reflect the current clinical challenges caused by carbapenem-resistant bacteria and the importance of infection prevention and control measures to mitigate further spread.

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Filippo Medioli of Policlinico di Modena, Italy. For more related content on the WHO Priority Pathogens List and new antibiotics in the pipeline, check out our previous episodes, Communicable E3 and E10 (see Literature).

Literature 

Communicable E3 - The New WHO Priority Pathogens List: which bugs to target first? June 2024. https://communicable.transistor.fm/episodes/communicable-e3-the-new-who-priority-pathogens-list-which-bacteria-to-target-first 

Communicable E10 - Pipeline update: new antibiotics & other antimicrobials that you might actually use. Sep 2024. https://communicable.transistor.fm/episodes/communicable-e10-pipeline-update-new-antibiotics-other-antimicrobials-that-you-might-actually-use 

Wagenlehner FM, et al. Cefepime-Taniborbactam in Complicated Urinary Tract Infection. N Engl J Med 2024 Feb. doi: 10.1056/NEJMoa2304748

Cohn J, et al. Accelerating antibiotic access and stewardship: a new model to safeguard public health. Lancet Infect Dis 2024 Sep. doi:  10.1016/S1473-3099(24)00070-7

Timsit JF, et al. When should I start broad-spectrum antibiotics? Intensive Care Med 2024 Sep. doi: 10.1007/s00134-024-07654-7 

Paterson DL. Antibacterial agents active against Gram Negative Bacilli in phase I, II, or III clinical trials. Expert Opin Investig Drugs 2024 Apr. doi: 10.1080/13543784.2024.2326028 

On the verge of a post-antibiotic reality, there is an urgent clinical need for new antibiotics. Luckily, new candidates are in the pipeline and older agents are getting a second breath of life through combination therapy. 

In this episode of Communicable, host Erin McCreary invites Dr. Markus Zeitlinger of the University of Vienna (Austria) and scientific expert for the European Medicines Agency (EMA) and Dr. Michael Dudley, president and CEO of Qpex Biopharma, to discuss antimicrobials in the clinical development pipeline.  Together they unpack how the WHO curate the priority list of pathogens and how companies adapt such lists into their antimicrobial development business plans. They also discuss the unique challenges and complexities of developing antibiotics, from return on investments and defining the ‘novelty’ of an agent to the conundrum of balancing post-market approval and antimicrobial stewardship. Beta-lactamase inhibitors and oral carbapenems in the pipeline targeting ‘the big three’ (Enterobacterales, Pseudomonas and Acinetobacter) are the primary focus.

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Benjamin Berinson of the Medical Centre Hamburg-Eppendorf (UKE), Germany. For more information on the WHO Priority Pathogens List and its 2024 update, check out our previous episode, Communicable E3 (see Literature). 

Literature 

Communicable E3 - The New WHO Priority Pathogens List: which bugs to target first? 17 June 2024. https://communicable.transistor.fm/episodes/communicable-e3-the-new-who-priority-pathogens-list-which-bacteria-to-target-first 

WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: World Health Organization; 17 May 2024. https://www.who.int/publications/i/item/9789240093461 

C. Le Terrier et al, NDM-9 resistance to taniborbactam. Lancet Infect Dis 23, 401-402 (2023). doi 10.1016/S1473-3099(23)00069-5     

P. B. Eckburg et al, Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. N Engl J Med 386, 1327-1338 (2022). doi: 10.1056/NEJMoa2105462 

A Study of Oral Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) Compared to Intravenous Imipenem-cilastatin in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (PIVOT-PO). https://clinicaltrials.gov/study/NCT06059846

Meiji Seika Pharma Initiated the Global Phase III Clinical Trials of OP0595, a Novel beta-Lactamase Inhibitor for Combatting Antimicrobial Resistance (AMR). Tokyo: Meiji Seika Pharma Ltd; 26 April 2023. https://www.meiji.com/global/news/2023/pdf/230426_01.pdf

The current H5N1 avian flu outbreak in poultry and dairy cows in the US has raised the alarm on bird flu and its transmission risk across species. At present, the virus has infected 100 million birds across 48 states and 196 dairy herds across 14 states. Luckily, the H5N1 avian flu, which is very lethal in birds, does not transmit easily into humans nor does it generally cause severe and systemic symptoms when humans are infected. Still, workers most exposed to these infected animals are testing positive with 14 human cases reported so far since 2022. 

In this Communicable episode, hosts Angela and Nav are joined by avian flu expert Ron Fouchier (Erasmus MC Rotterdam, Netherlands) to discuss the most recent developments of the outbreak in the US and the potential risks H5N1 virus poses to humans. Understanding of the virus from its first reported outbreak in Hong Kong in 1997 to its global prevalence today is reviewed. While H5N1 bird flu does not pose as a global human health concern at present, unchecked practices in the dairy, meat, and agricultural industry sectors, in which workers are exposed to the virus, threaten to change the status quo. Learn why the threat is even more paramount in fall when human influenza or seasonal flu is widespread, and to what extent the government should also be involved in prevention and containment measures before it becomes, in Ron’s words, another “missed opportunity.”          

This episode was edited by Kathryn Hostettler and peer-reviewed by Dr. Simon Galmiche of the Institut Pasteur, Université Paris Cité, Paris, France.

Literature

US Centers for Disease Control and Prevention (CDC). H5 Bird Flu: Current Situation. 2024. https://www.cdc.gov/bird-flu/situation-summary 

Only known to us since 2008, Candida auris is an emerging fungal pathogen spreading quickly around the world; alarmingly, it is most commonly found in healthcare settings. C. auris sets itself apart from other Candida species with its unique tolerance to high saline and temperature environments and propensity to develop antifungal resistances that promote its survival in hospitals and healthcare facilities. 

Hosts Emily McDonald and Navaneeth Narayanan are joined by fungal experts Dr. Jeffrey Rybak (St. Jude, Memphis TN) and Dr. Graham Snyder (UPMC, Pittsburgh PA) on their quest to better understand C. auris infections, the clinical challenges and knowledge gaps in C. auris research and discuss measures for prevention and containment on the levels of both the patient and the institution. 

The recent emergence of C. auris as a multidrug-resistant nosocomial pathogen and its global prevalence has raised more questions than answers. Why now? Why healthcare facilities? Does climate change play a role? Are humans to blame? Tune in to find out what the experts have to say on these questions, and stay to learn about the current therapies available, what is in the antifungal pipeline and how to approach treatment from a stewardship standpoint.

This episode was produced by Angela Huttner, edited by Kathryn Hostettler and peer-reviewed by Dr. Claudio Neidhöfer of University Hospital Bonn, Germany.

Literature

Satoh K, Makimura K, Hasumi Y, et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009 Jan;53(1):41-4. doi: 10.1111/j.1348-0421.2008.00083.x

Lee WG, Shin JH, Uh Y, et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011 Sep;49(9):3139-42. doi: 10.1128/JCM.00319-11

Pfaller MA, Diekema DJ, Turnidge JD, et al. Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016. OFID. 2019 March;6(S1): S79–S94. doi: 10.1093/ofid/ofy358

Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis. 2017 Jan 15;64(2):134-140. doi: 10.1093/cid/ciw691.

Clancy CJ, Nguyen MH. Emergence of Candida auris: An International Call to Arms. Clin Infect Dis. 2017 Jan 15;64(2):141-143. doi: 10.1093/cid/ciw696

Rybak JM, Cuomo CA, Rogers PD. The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris. Curr Opin Microbiol. 2022 Dec;70:102208. doi: 10.1016/j.mib.2022.102208