Highlights from ESCMID Global 2026
This year’s Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global, 17-21 April, Munich, Germany) attracted over 16,000 delegates from nearly 150 countries: Medical doctors, researchers, innovators, all gathered to understand current challenges in infectious diseases [1].
Anya Strokova, Therapeutic Area Lead, Infectious Diseases, Sergii Karas, Project Director, Cecilia Dignani, Director of Medical Monitoring for Infectious Diseases, and Liga Ulmane, Senior Director of Medical Monitoring, were among PSI’s representatives in Munich. Read on for their thoughts on the congress – including the most important takeaways surrounding antimicrobial resistance policies and new advances in the field that will impact infectious disease clinical trials of the future.
Sepsis: A new dawn in treatment
Sepsis was prominently featured at ESCMID Global – it remains a critical area of concern [2]. Focusing on three different trials, each signals a critical direction of how sepsis is perceived and will be treated in the future.
Seeing sepsis as a stratified, host-response disease
Sobi’s positive results in their phase 2a EMBRACE study of emapalumab in IFN-γ -induced sepsis were showcased again at ESCMID Global [3]. This trial reinforces that outcomes in sepsis are heavily driven by host biology (and different immune and inflammatory pathways). These data support the concept that in select patients, dysregulated host immune responses, such as excessive IFN-γ signaling, may be a more important determinant of outcomes than the infecting pathogen itself. The growing focus on immune phenotyping and biomarker-defined subgroups suggest that future success in sepsis will depend on identifying the right patients at the right stage of disease.
Infectious disease trials are becoming more operationally complex – requiring faster screening workflows, integrated biomarker testing, and tighter coordination between sites, laboratories, and vendors or partners. Biomarker-driven enrichment strategies, prospective stratification, and rapid diagnostic tools capable of identifying specific inflammatory signatures are therefore likely to be come central components of next-generation sepsis trial design.
Interpreting trial design in the context of outcomes
Inotrem’s ASTONISH study, evaluating nangibotide’s sTREM-1 blocking mechanism to treat septic shock, also demonstrated positive outcomes [4, 5]. Inotrem’s agreement with the FDA to refine their pivotal phase 3 trial is indicative of strong forward steps in sepsis: Perhaps traditional, fixed, two-arm RCTs in sepsis are structurally mismatched, and adaptive approaches may represent the future preferred trial model.
Repositioning antibiotics
The non-inferiority of temocillin to meropenem in GSK’s phase 3 trial added to the promising outlook for patients with sepsis. Carbapenem-sparing alternatives help preserve the effectiveness of the ecosystem, mitigating bacterial resistance. Antibiotic stewardship remains as crucial as ever.
The clear shift in how sepsis, and severe acute infections, will be studied and commercialized is evident. The “one-size-fits-all” model is dead – sepsis R&D is moving from broad empiricism to precision and ecosystem-driven development. The results from EMBRACE, ASTONISH, and ImmunoSep’s studies reinforce our growing optimism that precision immunotherapy for sepsis, long pursued but repeatedly limited by failed trials, may finally begin to deliver practice-changing advances by matching treatment to patients’ immune profiles. Sponsors will need to become more specialized and embrace precision and adaptive trial design to remain competitive.
Policies driving antimicrobial resistance (AMR) action
AMR is linked to almost 5 million global deaths per year [6], and the World Bank projects severe resistance scenarios could decrease global GDP by nearly 4% by 2050 [7]. Infection prevention and control (IPC) strategies effectively reduce infections and associated costs, not as an additional expenditure but a lifesaving, resource-saving approach.
ESCMID Global showcased an independent initiative (Gr-ADI) funded by Novo Nordisk, Wellcome, and the Gates Foundation [8], providing evidence-based actions on AMR. Relevant issues discussed during the congress included:
- Vaccination as an underutilized tactic: Preventing bacterial infections that necessitate antibiotic use would reduce transmission and complications, thus limiting antibiotic demand and resistance
- The shift from treatment to prevention: AMR requires a strategic shift with IPC and vaccination being most effective, and highly cost efficient
- Evolution of real-time surveillance: AMR surveillance is evolving to integrate genomics, rapid diagnostics, and non-traditional data for prompt threat detection
- Rapid treatment approaches: AMR can be minimized through diagnostic testing allowing earlier antibiotic de-escalation and shorter treatment durations, helping to reduce unnecessary antibacterial exposure once microbiological results are available
- Overcoming economic policy misalignment: Better incentives, coordinated funding, and specific usage targets are needed to align with antimicrobial value
- Implementing research priorities: Complex resistance mechanisms need more nuanced, PK/PD-informed metrics – such insights could transform global research into tangible national and local AMR impact
Initiatives such as Gr-ADI (and others, for example CARB-X or ECRAID) have made strong progress in funding, streamlining and coordinating clinical research networks and enabling innovation in infectious disease trials, but execution remains fragmented across sponsors, investigators, and regional networks. What is still missing is a consistently integrated operational partner that can bridge these groups, and translate funding and study design into efficient, globally-aligned trial delivery with predictable activation and enrollment.
A focus on Health Technology Assessments (HTAs) emphasized the economic value of AMR solutions by advocating for value-based pricing, and highlighted the societal benefit of new antimicrobials. HTAs are pivotal in facilitating a sustainable antibiotic market and informed policy guidance, ensuring responsible use and effective insurance coverage decisions.
AMR is forcing a fundamental redesign of clinical trials, shifting the focus from treatment alone to integrated prevention, surveillance, and stewardship. Future studies will need to capture not just efficacy, but ecological and population-level impact, otherwise they risk missing the true value of anti-infectious disease interventions.
Invasive fungal diseases: Emerging developments, the central role of host immunity, and innovations in trial design
Invasive fungal diseases (IFDs) are increasing in incidence, expanding in host range, and becoming more resistant, with profound global health implications. Their epidemiology reflects not only microbial evolution, but how modern medicine, immunity, environment, and global inequities intersect. ESCMID Global 2026 positioned mycology as a mainstream pillar of infectious diseases, not a niche subspecialty.
New antifungal agents
Key new antifungal agents at ESCMID Global 2026 were strongly aligned with WHO priorities [9], especially for Candida auris and azole-resistant Aspergillus.
- Phase 2b sub-analysis results of Olorofim (F2G, a first in class orotomide), oral, to target invasive aspergillosis (including azole-resistant Aspergillus) and rare molds (Lomentospora, Scedosporium and dimorphic fungi)
- The phase 2 TREAT-1 trial (, Elion Therapeutics, EL219/SF001, a novel polyene), weekly IV, to target early invasive mold infection
- Phase 1 data from Scynexis’ SCY-247, a next generation oral and IV triterpenoid to target invasive candidiasis including Candida auris
- Fosmanogepix, Basilea’s first-in-class Gwt1 inhibitor for Candida species and molds (Aspergillus, Fusarium, Lomentospora, Mucor), was showcased with late-breaker and poster data
- Mundipharma’s Rezafungin, a long-acting echinocandin to target candidemia/candidiasis, although already approved, ESCMID Global 2026 data focused on real world, early access, and use in OPAT and early discharge pathways due to the weekly dosing
Diagnosing IFD
At ESCMID Global 2026, plasma-based fungal cell-free DNA (cdDNA) testing using broad-range next-generation sequencing (NGS) emerged as one of the most promising approaches for diagnosing culture-negative IFD, important for high-risk patients when cultures fail, particularly when used alongside established tools such as GM, BDG, and targeted PCR.
More broadly, next-generation biomarkers, multiplex/NGS platforms, and radiomics are shifting IFD diagnosis away from culture-dependent confirmation toward earlier, probability-based detection using blood, respirometry samples, and quantitative imaging features.
Host immunity
The EFISG (ESCMID Fungal Infection Study Group) emphasized that IFD are complex host–pathogen syndromes, requiring integration of immunity, diagnostics, antifungal pharmacology, and stewardship.
An expansion beyond classic hosts is being observed: a shift from traditional neutropenic and transplant hosts to ICU patients, patients on immune-modulating therapies, and older populations with co-morbidities.
The EFISG strongly promoted an immunity-informed approach to mycology, emphasizing that host immune status is a key determinant of fungal disease risk, presentation, diagnostics, and outcomes. A future focus on integrating immune profiling into diagnostics, aligning antifungal stewardship with immune status rather than the pathogen alone, and clinical trial design means recognizing that successful management of IFD depends on immune recovery and timing as much as the antifungal therapy itself.
AI in IFD diagnostics, risk stratification, and decision support
AI in fungal diseases are a near-term clinical reality. Following on from ESCMID’s dedicated AI and machine learning in medical microbiology workshops last year in Zurich, Switzerland, the discussion continued at ESCMID Global 2026.
Diagnostics:
- AI-assisted digital microscopy (showing improved sensitivity and reduced inter‑observer variability)
- Machine learning applied to MALDI‑TOF MS spectra, improving discrimination between closely related fungal species and aiding early identification of rare molds
- AI-supported molecular diagnostics
Risk stratification and decision support:
- Early risk stratification models integrating EHR data, imaging, and laboratory trends to flag patients at high risk for invasive aspergillosis or candidiasis
- Clinical decision‑support systems to prioritize diagnostic testing and antifungal therapy before culture confirmation
- Predictive models for antifungal resistance, particularly in regions with high azole resistance in Aspergillus fumigatus
Several sessions this year highlighted AI beyond traditional microbiology, including using radiomics and deep learning models to differentiate between invasive fungal disease and bacterial or non-infectious filtrates in hematology patients, and use of AI image classifiers in superficial fungal infections.
Clinical trial design
Speakers at ESCMID Global 2026 repeatedly stressed that rare IFDs (e.g. Lomentospora, Scedosporium, Fusarium, rare yeasts) suffer from extremely low incidence, heterogeneous hosts and immune states, high baseline mortality, and lack of suitable comparators.
This makes traditional, large, randomized, pathogen specific RCTs unrealistic and ethically complex. Speakers explicitly noted growing alignment between ESCMID, EMA, FDA, and WHO that trial innovation is necessary.
The future of rare IFD trials will rely on:
- Basket and single arm designs
- Composite endpoints
- Adaptive and platform methodologies
- Global registries and real-world data
- Immunology-informed stratification
At ESCMID Global 2026, DOOR (Desirability of Outcome Ranking) was positioned as a powerful secondary framework to capture the real clinical value of antifungal therapies [10]. DOOR is not a replacement for efficacy endpoints, but a complementary, decision relevant framework that aligns better with real world risk–benefit tradeoffs, AMR concerns, and stewardship goals.
IFD are an escalating global health threat driven by changing epidemiology and antifungal resistance, with persistently high mortality due largely to delayed or inadequate diagnosis. ESCMID emphasized that improving patient outcomes requires rapid deployment of advanced diagnostics, expansion of the antifungal drug pipeline now emerging, and stronger antifungal stewardship and surveillance worldwide.
Breakthroughs and perspectives
C. difficile
Positive phase 2 data for AZD5148 (AstraZeneca), CSR3123 (Crestone Inc.), and ibezapolstat (Acurx Pharmaceuticals) were reported, alongside several ongoing phase 1 and 2 programs (results pending, including new interventions from Destiny Pharma/Sebela Pharmaceuticals, Lumen Bioscience, Vendanta Biosciences, and Exeliom Biosciences).
Together, they emphasize a rapidly advancing pipeline of microbiome-sparing antibiotics and live therapeutics, reinforcing a future for C. difficile prevention that is increasingly focused on targeted, recurrence-preventing strategies, rather than broad-spectrum treatment.
Gram-negative bacteria
A robust, late-stage pipeline combining optimized β-lactam/β-lactamase inhibitor regimens, novel modalities, and expanded indications is collectively strengthening the arsenal against resistant gram-negative infections.
- Gremumab (AstraZeneca): Data from the phase 2 GREAT-2 trial demonstrated a significant reduction in bacterial load vs. placebo in patients with bronchiectasis and chronic Pseudomonas aeruginosa, highlighting a novel antibody approach
- Tebipenem pivoxil (Spero/GSK): A subgroup analysis from the phase 3 PIVOT-PO trial supports the efficacy of tebipenem pivoxil in cUTI and acute pyelonephritis
- Cefepime/emmetazobactam (Allecra Therapeutics): Data from a post hoc analysis of the phase 3 ALLIUM trial showed strong overall response and microbiological eradication vs. piperacillin/tazobactam in acute pyelonephritis
- Cefepime/nacubactam and aztreonam/nacubactam (Meiji Seika Pharma): Phase 3 data from the INTEGRAL-2 trial demonstrated efficacy and safety vs. best available therapies in serious infections caused by carbapenem-resistant Enterobacterales (such as cUTI/AP, HABP/VABP, and cIAIA)
- Sulbactam-durlobactam (Innoviva Specialty Therapeutics): The phase 3 ATTACK trial was presented, comparing sulbactam-durlobactam vs. colistin (both with imipenem/cilastatin) for HABP/VABP, alongside an ongoing phase 2 study in pediatric Acinetobacter baumannii-calcoaceticus complex infections
Clinical trials will increasingly prioritize pathogen-specific enrollment, superiority or non-inferiority to optimized SoC, inclusion of resistant subpopulations, and lifecycle expansion strategies (pediatric, adjunctive biologics, and so on).
Antivirals
The antiviral pipeline is becoming increasingly diverse and mechanism-driven, spanning small molecules, biologics, and repurposed agents, with a strong focus on resistant and immunocompromised patients.
- HSV: Pritelivir (AiCuris) met its phase 3 primary endpoint in resistant HSV infections – a significant advance for patients with limited treatment options
- Broad antiviral pipelines: SymBio Pharmaceuticals’ brincidofovir (IV and oral) is progressing across multiple indications, and Pulmotect’s PUL-042 is proving to be effective across different indications
- CMV and transplant-associated infections: A mix of repurposed (artesunate) and novel (EV-100, Cytogam) agents are being explored, highlighting continued unmet need
- Respiratory viruses: Positive phase 2 signals from mid-stage candidates (zelipacavir and DAS-181) demonstrate ongoing momentum in RSV and parainfluenza
- BK virus and novel modalities: Monoclonal antibodies and anti-sense oligonucleotides signal a shift toward targeted, mechanism-driven approaches in niche but high-risk viral infections
Antiviral trials will increasingly need to target highly specific patient subgroups, incorporate resistance-driven endpoints, and accommodate novel modalities. This will increase trial design complexity, but also result in more clinically meaningful outputs.
Pediatric infections: Prevention and prophylaxis
ESCMID Global 2026 highlighted a clear shift toward proactive prevention of pediatric infections. Recent approvals of RSV-targeting monoclonal antibodies (clesrovimab and nirsevimab) underscore momentum in immunization strategies for infants.
Additionally, advances in active immunization, such as GlaxoSmithKline’s investigational GSK4406371 vaccine targeting MMRV with a new seed approach could deliver broad, durable protection in children.
Pediatric infectious disease management is moving upstream: From treatment to prevention and prophylaxis. Integrated approaches, spanning long-acting antibodies and next-generation vaccines could redefine how this potentially vulnerable population are treated, and how early-life infections are avoided.
mRNA vaccines
The vaccine landscape is rapidly evolving toward platform-based, highly adaptable technologies – particularly mRNA – alongside renewed interest in bacterial vaccines as a preventative tool against AMR (although much research remains early-stage).
- Vaccines targeting AMR: Early-stage programs targeting pathogens such as Klebsiella pneumonia remain in development across multiple biotechs, reflecting growing interest in prophylactic strategies against drug-resistant bacteria – although no such vaccines are approved yet
- Moderna’s mRNA vaccine suite: Moderna presented a number of diverse infectious disease mRNA vaccines, including mRNA-1653 (a combination respiratory vaccine candidate), mRNA-1345 (RSV; advancing through late stage development with strong immunogenicity and revaccination potential, mRNA-1189 (Epstein-Barr virus), and mRNA-1647 (cytomegalovirus); all of which further demonstrate post-pandemic use cases of mRNA vaccines
The success of the COVID-19 vaccines catalyzed a broader pipeline of mRNA vaccines and vaccine platforms across infectious diseases, with ongoing innovation focusing on improving stability, delivery, and immunogenicity, while expanding into new targets.
AI and large language models (LLMs)
Large language models (LLMs) can assist with antimicrobial susceptibility testing (AST), but the complexity of resistance mechanisms limits minimum inhibitory concentration prediction accuracy near clinical thresholds.
At this stage, LLMs should not be solely relied upon in clinical environments, as their inconsistent reproducibility should prompt sponsors and clinicians to thoroughly evaluate every output.
Final takeaways
Despite multiple positive phase 3 readouts and approvals, most advances in antibiotics remain iterations on existing classes, with progress driven by optimization rather than fundamentally new mechanisms – meaning resistance will remain a moving target. The noticeable shifts are towards prevention, precision, and modality diversification.
We now have a broader and more innovative toolkit of small molecules, monoclonal antibodies, live biotherapeutics, antisense oligonucleotides, and mRNA to combat the broad spectrum of infection, and target high-value niches. With this, however, comes increased complexity in clinical trial design – something for sponsors to capitalize on to increase their differentiation.
Ultimately, the future of infectious disease management lies in prevention, precision targeting, and especially evident at ESCMID Global 2026 [1]: Diversified modalities that move beyond traditional anti-infectives.
Abbreviations
AMR, antimicrobial resistance;
AP, acute pyelonephritis;
(1→3)-β-D-Glucan;
BK virus, Human polyomavirus 1;
cIAI, complicated intra-abdominal infection;
CMV, cytomegalovirus;
COVID-19, coronavirus disease 2019;
cUTI, complex urinary tract infection;
DOOR, Desirability of Outcome Ranking;
EFISG, ESCMID Fungal Infection Study Group;
EHR, Electronic Health Record;
EMA, European Medicines Agency;
ESCMID, European Society of Clinical Microbiology and Infectious Diseases;
FDA, Food and Drug Administration;
, Galactomannan;
Gr-ADI, Gram-Negative Antibiotic Discovery;
GSK, GlaxoSmithKline;
HABP/VABP, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia;
HSV, herpes simplex virus;
HTA, Health Technology Assessment;
ICU, Intensive Care Unit;
IFN-γ, interferon-gamma;
IPC, infection prevention and control;
IFD, invasive fungal diseases;
LLM, large language models;
MALDI‑TOF MS, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry;
MDR, multidrug resistance;
MMRV, measles, mumps, rubella, varicella;
mRNA, messenger RNA;
NGS, next generation sequencing;
OPAT, Outpatient Parenteral Antifungal Therapy;
, polymerase chain reaction;
PK/PD, pharmacokinetics/pharmacodynamics;
RCT, randomized controlled trial;
RSV, respiratory syncytial virus;
SoC, standard of care;
sTREM-1, soluble triggering receptor expressed on myeloid cells-1.
References
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