In this episode of Communicable, Angela Huttner and Josh Davis are joined by Brett Mitchell, Aline Wolfensberger and Lauren Clack to discuss the HAPPEN trial to prevent hospital-acquired pneumonia led by Mitchell--and the important studies leading up to it [1-3]. The episode also explores trial designs used in their research that are both creative and practical, such as stepped-wedge and implementation trials, and how these approaches can bridge the gap between research and real-world practice.

References

1. Mitchell B, “The hospital acquired pneumonia prevention (HAPPEN) study: a multi-centre randomised controlled trial” in ESCMID Global 2026. https://online.escmid.org/media-6348-hospital-and-ventilator-associated-pneumonia-new-insights-on-prevention-diagnosis-and-treatment (Presentation).
2. White NM, et al. Effectiveness of oral care for the prevention of non-ventilator hospital-acquired pneumonia (HAPPEN): a multicentre, stepped-wedge, cluster-randomised trial in Australia. Lancet Infect Dis 2026. DOI: 10.1016/S1473-3099(26)00235-5.
3. Wolfensberger A, et al. Prevention of non-ventilator-associated hospital-acquired pneumonia in Switzerland: a type 2 hybrid effectiveness–implementation trial. Lancet Infect Dis 2023. DOI: 10.1016/S1473-3099(22)00812-X.

Further reading

• HAPPEN study website: Study overview and resources www.happenstudy.com
• Cassini A, et al. Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study. PLoS Med 2016. DOI:  10.1371/journal.pmed.1002150. 
• Pronovost P, et al. An Intervention to Decrease Catheter-Related Bloodstream Infections in the ICU. NEJM. DOI: 10.1056/NEJMoa061115. 
• Bion J, et al. ‘Matching Michigan’: a 2-year stepped interventional programme to minimise central venous catheter-blood stream infections in intensive care units in England. BMJ Quality & Safety 2013. DOI: 10.1136/bmjqs-2012-001325.
• Dixon-Woods M, et al. Explaining Matching Michigan: an ethnographic study of a patient safety program. Implementation Sci 2013. DOI: 10.1186/1748-5908-8-70.  
• Clack L, et al. Hybrid effectiveness-implementation studies in infection prevention and infectious diseases: a narrative review. CMI 2025. DOI: 10.1016/j.cmi.2025.10.022.
• Hospital Acquired Pneumonia Prevention (HAPPEN) Study: Statistical Analysis Plan
  https://www.medrxiv.org/content/10.1101/2025.08.14.25333719v1
• Oral care practices and hospital-acquired pneumonia prevention: A national survey of Australian nurses
  https://pubmed.ncbi.nlm.nih.gov/38724299/
• Nurses' experiences of providing oral care to hospitalised patients: A qualitative study
  https://pubmed.ncbi.nlm.nih.gov/40450434/

In this episode of Communicable, Thomas Tängdén and Rekha Pai Mangalore return for part 2 of the ‘We will make you love PK/PD’ series. In this round, they are joined by Iris Minichmayr (Austria) and Phil Selby (Australia) for a deep dive into how PK/PD data and principles can be used as integral clinical tools to support dosing decisions. They break down technical concepts of pharmacometrics such as population PK models, Monte Carlo simulations, probability of target attainment (PTA), and cumulative fraction of response (CFR), helping to make these approaches more accessible to everyday clinical practice.

This episode was edited by Kathryn Hostettler. The executive producer of Communicable is Angela Huttner.

Further reading

• Tängdén T, et al. Personalised patient management and infection prevention: current evidence and future perspectives. In: ESCMID Global 2025. Available on ESCMID Media: https://media.escmid.org/videos/01K7HWCJAHZ464H3XXK97SZ842

In this episode of Communicable, Emily McDonald and Josh Davis are joined by Roger Lewis (USA) and Ian Marschner (Australia) to compare and contrast Bayesian and frequentist statistical approaches. The panel discusses the fundamental principles of both methods, common misconceptions, and the extent to which they are often more similar than many realise. Together, they explore their use in clinical trial design, analysis, and reporting, including adaptive trials and sequential learning. Additional topics include sample size misconceptions, regulatory versus clinical thresholds, and the challenges of interpreting post hoc reanalyses of negative trials.

This episode was edited by Kathryn Hostettler and the executive producer of Communicable is Angela Huttner. 
 

Further reading:

• Berry SM, et al. Bayesian Adaptive Methods for Clinical Trials (Chapman & Hall/CRC Biostatistics Series). Boca Raton (FL): CRC Press; 2010. 
• FDA Guidance Document: Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products FDA, 2026, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-bayesian-methodology-clinical-trials-drug-and-biological-products
• Lee TC, et al. Contextualizing the use of corticosteroids in severe Pneumocystis jirovecii pneumonia through a Bayesian lens. CMI Comms 2025, https://www.cmi-comms.org/article/S2950-5909(25)00082-4/fulltext
• Livingston EH and Lewis RJ. JAMA Guide to Statistics and Methods, https://jamaevidence.mhmedical.com/Book.aspx?bookId=2742
• Marschner I. Confidence distributions for treatment effects in clinical trials: Posteriors without priors. Stat Med 2024, doi: 10.1002/sim.10000.
• Whitehead J. The design and analysis of sequential clinical trials. Revised 2nd ed. Chichester: John Wiley & Sons; 1997.

In this bonus episode of Communicable, hosts Anne-Grete Märtson and Angela Huttner invite Martin Grobusch (University of Amsterdam; ESCMID Emerging Infections Subcommittee) and Daniel Bausch (National University of Singapore, London School of Hygiene & Tropical Medicine, and Geneva Graduate Institute) to discuss the Bundibugyo ebolavirus outbreak currently ongoing in the Democratic Republic of Congo and Uganda. Clinical and virological differences between Bundibugyo and Zaire ebolaviruses are discussed, as are the particular challenges for diagnosis, treatment, and prevention confronting healthcare workers of this outbreak. The episode accompanies two new publications in CMI Communications and CMI:

• Gupta N, Mora-Rillo M, Gkrania-Klotsas E, et al. Bundibugyo ebolavirus (BDBV): what first responders/clinicians need to know. CMI Communications, 2026; 2 (DOI: 10.1016/j.cmicom.2026.105207) 
• Gupta N, Marta Mora-Rillo, Gkrania-Klotsas E, et al. Bundibugyo ebolavirus outbreak in the Democratic Republic of the Congo and Uganda: rapid assessment from the ESCMID Emerging Infections Subcommittee. Clin Microbiol Infect, 2026 (DOI: 10.1016/j.cmi.2026.05.042)

Our editors – Marc Bonten, Erin McCreary, Anne-Grete Märtson, Angela Huttner, and Josh Davis – are back for part two of the ESCMID Global Late Breakers series, summarising five more late-breaking trials presented at ESCMID Global 2026. They discuss the trials' strengths and weaknesses, and whether their results should change practice. 

The five trials presented in this half of the series are listed below, and links to their respective sessions can be watched and rewatched on the ESCMID Global Virtual Platform. Links to corresponding abstracts and publications where available are provided as well.

Conflict of interest/involvement in the trials:

• Marc Bonten was the chair of the E.mbrace trial's steering committee
• Josh Davis is global co-lead of the SNAP trial
• Josh Davis was a site investigator on the E.mbrace trial
• Angela Huttner was an independent/unpaid member of the E.mbrace trial's steering committee and an investigator on the precursor phase 1 trial testing the E. coli vaccine

PROCALBAN trial (Late-breaking clinical trials in sepsis management)

• Chowdhury F, et al. Use of Procalcitonin Point-Of-Care Testing to Guide De-Escalation of Antibiotic Therapy in Adult Sepsis Patients in a Tertiary Hospital in Bangladesh: A Randomised Controlled Open-Label Trial, Preprints with The Lancet, doi: 10.2139/ssrn.6541698

BENEFICIAL trial (Late-breaking clinical trials in sepsis management) 

• De Cock PA, et al. Bedside model-informed precision dosing of vancomycin in severely ill neonates and children in Belgium (the BENEFICIAL trial): a multicentre, randomised controlled trial. Lancet Child Adolesc Health, doi: 10.1016/S2352-4642(25)00385-2  

SNAP trial (Late-breaking clinical trials in sepsis management) 

• Bowen A. Adjunctive clindamycin for treatment of Staphylococcus aureus bacteraemia: a randomised controlled trial within the S. aureus Network Adaptive Platform (SNAP), abstract

Adjunctive betamethasone treatment of hypoxemic adults hospitalised with Mycoplasma pneumoniae community-acquired pneumonia: an open-label, multicentre, randomised, controlled trial (Late-breaking research from The Lancet)

• Hagman K, et al. Adjunctive betamethasone treatment of hypoxaemic adults hospitalised with Mycoplasma pneumoniae community-acquired pneumonia: an open-label, multicentre, randomised, controlled trial. Lancet 2026, doi: 10.1016/j.lanepe.2026.101610

E.mbrace trial (Vaccines: landmark trials and preventive immunisation)

• Cohen CA, et al. Randomised phase III trial of a 9-valent vaccine (ExPEC9V) for prevention of invasive Escherichia coli disease (IED) in older adults (E.mbrace), abstract

The Swiss multicentre phase 1, first-in-human trial testing the conjugate E. coli vaccine:

• Huttner A et al. Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Lancet Infect Dis 2017: May;17(5):528-537

The ESCMID Global Late Breakers series returns to Communicable! Five CMI Communications editors – Marc Bonten, Josh Davis, Angela Huttner, Anne-Grete Märtson, and Erin McCreary – handpicked five late-breaking trials presented at ESCMID Global 2026 to summarise their  findings and discuss whether the results will change their practice. This is part one of the two-part series. 

Trials presented are listed below and links to their respective sessions can be watched and rewatched on the ESCMID Global Virtual Platform. Links to corresponding publications, if available, and mentioned related articles are provided as well.

The FAST trial (Late-breaking research from JAMA)

• Banerjee R, et al. Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia. The FAST Randomized Clinical Trial, doi: 10.1001/jama.2026.5487 
• Srinivasan A. A Multinational Trial of Rapid Antimicrobial Susceptibility Testing. Is FASTer Better?, doi: 10.1001/jama.2026.5504

The CEFMEC trial (Poster session)

• Hayakawa K, et al. Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli, Antimicrob Agents Chemother 2023, doi: 10.1128/aac.00510-23

The COBRA trial (Late-breaking trials in surgical infection prevention)

• Overdevest AG, et al. Antibiotic treatment for 1 day versus 4-7 days in patients with acute cholangitis after adequate endoscopic biliary drainage (COBRA): study protocol for a randomized controlled trial. Trials, doi: 10.1186/s13063-026-09524-7

The DOTS trial, a secondary analysis (Late-breaking research from JAMA)

• Lodise, TP, et al. Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial, JAMA 2026, doi: 10.1001/jamanetworkopen.2026.11652 
• Walls G, et al. Patient-reported Perceptions, Experiences, and Preferences Around Intravenous and Oral Antibiotics for the Treatment of Staphylococcus aureus Bacteremia: A Descriptive Qualitative Study, Clin Infect Dis 2026, doi: 10.1093/cid/ciaf522
• Turner  NA , et al.  Dalbavancin for treatment of Staphylococcus aureus bacteremia: the DOTS randomized clinical trial. JAMA 2025, doi: 10.1001/jama.2025.12543 

Maribavir for clinically significant cytomegalovirus infection in hematopoietic cell transplantation: a real-world retrospective international study of the Infectious Disease Working Party of EBMT (Late-breaking research from The Lancet)

• Paviglianiti A, et al. Maribavir for clinically significant cytomegalovirus infection in haematopoietic cell transplant recipients in Europe: a real-world multicentre retrospective registry study. Lancet 2026. doi: 10.1016/S1473-3099(26)00144-1

In this collaborative episode of Breakpoints and Communicable, the hosts revisit the “trial run” session from ESCMID Global, a format designed to facilitate critical discussion of major infectious diseases trials. This episode focuses on two studies addressing bloodstream infections caused by third‑generation cephalosporin-resistant Enterobacterales [1].

Mical Paul (Rambam Health Care Campus, Israel) joins the podcast to discuss the PETER PEN trial [1,2], comparing piperacillin/tazobactam with meropenem, including its design, interim analyses, and interpretation alongside prior data such as MERINO. The episode also features Jesús Rodríguez‑Baño (University of Seville, Spain), who presents a post hoc analysis of the ASTARTE trial [1,3], comparing temocillin and carbapenems.

This episode was edited by Lacy Worden and was peer reviewed by Jeanette Bouchard (Duke Antimicrobial Stewardship Outreach Network (DASON) Durham, NC, USA).

References

1. Paul, M., & Rodríguez-Baño, J. (2026, April 20). The trial run: treatment of ESBL bacteraemia - off to never-never land. [Presentation]. ESCMID Global 2026, Munich, Germany. ESCMID Global Virtual Platform.
2. Bitterman R, Koppel F, Mussini C, et al. Piperacillin-tazobactam versus meropenem for treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacteriaceae: a study protocol for a non-inferiority open-label randomised controlled trial (PeterPen). BMJ Open. 2021;11(2):e040210. Published 2021 Feb 8. doi: 10.1136/bmjopen-2020-040210 
3. Marín-Candón A, Rosso-Fernández CM, Bustos de Godoy N, et al. Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial [Internet]. BMJ Open. 2021 Sep 27;11(9):e049481. doi: 10.1136/bmjopen-2021-049481 

Further reading

• Harris PNA, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA. 2018;320(10):984–994. doi: 10.1001/jama.2018.12163.

This is a short message to Communicable listeners to inform them that the next episode will be released on Friday, 8 May, as it is a collaboration episode with Breakpoints, the podcast of the Society of Infectious Diseases Pharmacists. It will cover the two trials presented in Munich during ESCMID Global's late-breaker Trial Run session.

Communicable is launching a new series on everything related to pharmacokinetics (PK) and pharmacodynamics (PD). Kicking off this series are hosts Thomas Tängdén, Erin McCreary and Angela Huttner, and invited guests Amy Legg and Rekha Pai Mangalore. They walk us through key parameters and terms of PK/PD, such as volume of distribution, minimum inhibitory concentration (MIC), epidemiological cut-off value (ECOFF), and PK/PD indices, laying the foundation to better comprehend clinical applications such as setting a clinical breakpoint and how it guides therapeutic drug monitoring (TDM). This first episode encompasses a broad scope across PK/PD theory, preparing the listener for subsequent episodes that will explore these topics with greater depth and make you love PK/PD. 

This episode was peer-reviewed by Ummu Afeera Zainulabid of the International Islamic University, Kuantan, Malaysia.   

Terms and definitions 

• ADME, a drug’s journey through the body: absorption, distribution, metabolism, excretion
• Volume of distribution, a parameter describing the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma
• Clearance, the volume of blood cleared of drug per unit time
• Half-life, the time required for the concentration of a drug to decrease to half of its initial amount in the body
• Loading dose, a larger initial dose designed to rapidly bring drug levels into the therapeutic range
• Steady state, an equilibrial condition in which the rate of input of a drug is equal to the rate of its output
• MIC, minimum inhibitory concentration
• ECOFF, epidemiological cut-off value: the highest MIC value of isolates that are not known to have resistance and are therefore considered representative of wild-type bacterial isolates
• Clinical breakpoint setting, takes into account drug dosing, PK/PD, site of infection, clinical data; what we think is the breakpoint for the lab to call a bacterial organism susceptible to a drug
• PK/PD index, a parameter that describes the observed antimicrobial activity of an antimicrobial; there are three different indices: 
  1. T>MIC (bacterial killing depends on the drug concentration’s remaining higher than the MIC over time)
  2. Cmax/MIC (bacterial killing depends on the drug’s peak concentration)
  3. AUC/MIC (bacterial killing depends on the area under the curve over the MIC)
• TDM, therapeutic drug monitoring

Further reading

• Mouton JW, et al. MIC-based dose adjustment: facts and fables. J Antimicrob Chemother 2018. doi:10.1093/jac/dkx427
• Märtson A, et al. The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments. Lancet Infect Dis 2025. doi: 10.1016/S1473-3099(25)00155-0
• Eagle H and Musselman AD. The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms. J Exp Med 1948. doi: 10.1084/jem.88.1.99

This is the first episode of the 'Quarterly catchup' series, in which CMI Communications editors discuss important and useful articles that have come out in the last 3 months to understand their results and potential clinical impact. In this inaugural episode of 'Quarterly catchup', Emily McDonald (Canada), Thomas Tängdén (Sweden) and Navaneeth Narayanan (USA) convene to discuss clinical microbiology and infectious diseases studies published in the first quarter of 2026 [1-6]. From Wolbachia-infected mosquitoes reducing dengue infection to exploration of antibiotic combination therapies against multidrug-resistant organisms, our hosts summarize six articles they found the most interesting, and discuss whether they can and should change clinical practice. 
 
This episode was peer reviewed by Connor Prosty of McGill University, Montréal, Canada.  

References

1. Lim JT, et al. Dengue suppression by Male Wolbachia-Infected mosquitoes. NEJM 2026. doi: https://doi.org/10.1056/NEJMoa2503304 
2. Escrihuela-Vida F, et al. Adjunctive Fosfomycin for the Treatment of Staphylococcus aureus Bacteremia: A Pooled Post Hoc Analysis of Individual Participant Data From 2 Randomized Trial. Clin Infect Dis 2026. doi: https://doi.org/10.1093/cid/ciaf387 
3. Baldanzi G, et al. Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals. Nat Med 2026. doi: https://doi.org/10.1038/s41591-026-04284-y.
4. Quentin Vallé, et al. Evaluating the antibacterial activity of ceftazidime/avibactam and aztreonam combinations against multidrug-resistant Stenotrophomonas maltophilia complex isolates in a hollow fibre infection model.  Clin Microbiol Infect 2026. doi: https://doi.org/10.1016/j.cmi.2026.02.010 
5. Rana AI, et al. Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges. NEJM 2026. doi: https://doi.org/10.1056/NEJMoa2508228 
6. Donovan J, et al. Genotype-stratified adjunctive dexamethasone for tuberculous meningitis in HIV-negative adults: a randomized controlled phase 3 trial. Nat Med 2026. doi: https://doi.org/10.1038/s41591-025-04138-z 

Further reading

• Thwaite GE, et al. Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults. NEJM 2004. doi: https://doi.org/10.1056/NEJMoa040573 
• Behrmann LV. “The specimen is never wrong”: the pathologist behind Wolbachia. CMI Communications, 2026. doi: https://doi.org/10.1016/j.cmicom.2026.105185                

In this episode of Communicable, hosts Angela Huttner and Marc Bonten invite two members of the ESCMID Emerging Infections Subcommittee, Martin Grobusch (Amsterdam, Netherlands) and Pikka Jokelainen (Copenhagen, Denmark), to discuss infectious disease outbreaks. Sparked by the Subcommittee's beloved 'Epi Alert', which identifies and tracks outbreaks around the world, the episode covers common missteps and underestimated challenges in handling new outbreaks, the effects of climate change, and what 'One Health' really means. 

This episode was peer reviewed by Ummu Afeera Zainulabid of the International Islamic University Malaysia, Kuantan, Malaysia.

Further reading

• Epi Alert. https://www.escmid.org/science-research/emerging-infections-subcommittee/eis-activities/
• Pellejero-Sagastizábal G, et al. Delayed correct diagnoses in emerging disease outbreaks: historical patterns and lessons for contemporary responses. CMI 2025. https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(25)00169-7/fulltext 
• One Health High-Level Expert Panel (OHHLEP), et al. One Health: A new definition for a sustainable and healthy future. PLoS Pathogens 2022. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010537 
• Swiss Tropical and Public Health Institute News. https://www.swisstph.ch/en/news