Infectious diseases have always evolved in response to emerging therapeutics – something Alexander Fleming warned of in his 1945 Nobel Prize lecture. What is changing now is the degree to which clinical practice must adapt. Here, Gerry Hughes reports from the British Society for Antimicrobial Chemotherapy New Agents Conference on the pressures on hospital systems from emergent fungal and viral threats, and the therapeutic innovations to tackle them.

Across secondary care, clinicians are encountering infections that are increasingly resistant to treatment and associated with complex patient populations. At the same time, therapeutic pipelines remain unpredictable.

Opening the recent British Society for Antimicrobial Chemotherapy (BSAC) New Agents Conference, its president Professor Andrew Seaton, consultant in infectious diseases and general medicine at NHS Greater Glasgow and Clyde, framed antimicrobial resistance (AMR) as a ‘supreme global threat’ demanding urgent clinical and scientific action.

The scale of the challenge is already clear. AMR is directly attributable to approximately 1.3 million deaths globally.

The trajectory in the UK is equally concerning, with the UK Health Security Agency (UKHSA) estimating that in 2024 there were nearly 400 antibiotic-resistant infections reported each week and that the number of deaths in people with a resistant infection increased from 2,041 deaths in 2023 to 2,379 in 2024.

BSAC New Agents spotlights complex infectious disease landscape

Bacterial pathogens are frequently at the forefront of the clinician psyche when considering AMR.

Speaking during the BSAC New Agents Conference, Dr Colin Brown, infectious disease and medical microbiology consultant at the UKHSA, warned that the epidemiological trends around bacterial resistance are deeply concerning. ‘Everything that we’re really worried about is not going in the right direction,’ he told delegates.

However, fungi and viruses also pose present and emerging threats. Invasive fungal infections are arguably an under-recognised driver of global infectious disease mortality.

Recent data suggests that, globally, around 6.5 million people develop invasive fungal infections each year, resulting in approximately 2.5 million directly attributable deaths. Respiratory viruses remain a major driver of winter hospital admissions, and influenza continues to place substantial pressure on healthcare systems.

In tandem with these pressures, the development pipeline for new treatments remains fragile. As Professor Seaton concluded in his opening remarks: ‘The pipeline is weak, and further innovation is needed to stimulate it.’

Against this backdrop, discussions at the BSAC New Agents Conference highlighted how clinicians are confronting an increasingly complex infectious disease landscape, not only in bacterial resistance, but also in emerging fungal pathogens, evolving respiratory viruses and the urgent need for new therapeutic strategies.

The growing burden of invasive fungal disease

Invasive Aspergillus has become one of the most clinically concerning fungal diseases. The estimated global incidence of invasive aspergillosis now exceeds 2.1 million cases – a dramatic increase from earlier estimates of around 200,000 cases per year in 2012.

Much of this increase reflects improved recognition of invasive aspergillosis in patient groups such as those with chronic lung disease, lung cancer and critical illness.

Despite advances in antifungal therapy, outcomes remain poor. Mortality at 12 weeks is typically 20–40%, with many infection-related deaths occurring within the first six weeks after diagnosis.

For clinicians, these infections are becoming more complex to manage as the population at risk expands to include patients receiving modern immunosuppressive therapies, biological treatments and advanced cancer therapies.

Rethinking treatment approaches to invasive fungal disease

Against this backdrop, Professor Tom Harrison, professor of infectious diseases and medicine at City St George’s, University of London, and honorary consultant at St George’s University Hospitals NHS Foundation Trust, called for a reassessment of combination antifungal therapy.

In a recent personal view published in The Lancet Infectious Diseases, Professor Harrison and co-author Professor Thomas Walsh argued that the current reliance on triazole monotherapy is based on a single randomised controlled trial and may no longer be sufficient in many high-risk patients with invasive aspergillosis.

The duo further highlighted evidence from a randomised trial comparing voriconazole plus the echinocandin anidulafungin with voriconazole alone.

Although the study was conducted more than a decade ago and the trial narrowly missed statistical significance for its primary endpoint, Professor Harrison noted that combination therapy was associated with a clinically meaningful reduction in six-week mortality of around 30%. Importantly, the regimen was well tolerated, with no increase in treatment discontinuation.

Professors Harrison and Walsh argue that such combinations may ‘increase efficacy through synergistic interaction and, if so, could allow reduced dosing, duration, toxicity and cost within optimised regimens’.

Such clinical trials are also supported by a substantial body of laboratory and animal model research, Professor Harrison noted, supporting the biological rationale for antifungal combinations. Triazoles and echinocandins target different fungal pathways and when used together can produce synergistic antifungal activity in experimental models.

Given the severity of invasive infection, optimising initial therapy is essential. Delaying combination treatment until salvage therapy may be less rational, according to Professor Harrison, especially if prior exposure to antifungal agents has already occurred.

The emerging threat of Candidozyma auris

Like invasive aspergillosis, Candidozyma auris appears on the World Health Organization’s fungal priority pathogens list and is classified in the highest ‘critical’ category.

Its emergence has also brought renewed attention to the infection prevention and control challenges associated with multidrug-resistant fungi in healthcare environments.

Dr Johanna Rhodes, honorary research fellow at Imperial College London and assistant professor in the School of Biosciences at the University of Birmingham, described a potential and lurking ‘crisis’ in her BSAC session focusing on Candidozyma auris.  

First described in 2008, the pathogen has now been reported in more than 45 countries. Resistance patterns are particularly concerning, says Dr Rhodes, as more than 87% of isolates demonstrate resistance to fluconazole, and pan-resistant strains have been reported.

Unlike many other Candida species, Candidozyma auris can persist in the hospital environment for prolonged periods. The organism has been detected on bed rails, ventilators, infusion pumps and other high-touch surfaces, allowing outbreaks to persist despite standard infection prevention measures.

In England, it became a notifiable pathogen in April 2025, reflecting increasing concern around healthcare-associated outbreaks. Recent surveillance in England reported 86 new cases between April and September 2025, with several NHS Trusts experiencing prolonged outbreaks.

A recent UKHSA report warned that ‘hospital outbreaks can be disruptive and costly due to the substantial service disruption resulting from measures put in place to reduce risk to patients and to control transmission’.

Therapeutic options remain limited. Echinocandins are currently recommended as first-line therapy, but resistance can develop, particularly in anatomical niches such as the urinary tract where drug penetration is suboptimal.

Similar to the invasive aspergillosis scenario, there is a lack of evidence on combination therapies to treat Candidozyma auris. However, Dr Rhodes questioned whether echinocandin monotherapy is advisable for Candidozyma auris given the propensity for resistance development and experiences with resistance development for other fungal pathogens receiving monotherapy.

Therapeutics for fungal disease

Encouragingly, several new antifungal agents are emerging for difficult to treat fungal diseases, which were highlighted at the BSAC New Agents Conference.

Fosmanogepix is the prodrug of manogepix and represents a new class of antifungal agents that inhibit the fungal Gwt1 enzyme, leading to disruption of cell wall synthesis. It is currently being investigated in clinical trials for invasive mould infections and candidaemia. Results of a phase 2 trial have recently been published on its use for the treatment of Aspergillus species and rare moulds.

Ibrexafungerp, is an oral first-in-class, non-azole, triterpenoid antifungal that inhibits synthesis of a fungal cell wall polymer. While licensed in the US for vulvovaginal candidiasis, it is currently being evaluated as a treatment option for invasive candidiasis and candidemia caused by Candidozyma auris.

Olorofim is an oral, first-in-class antifungal which inhibits the fungal enzyme dihydroorotate dehydrogenase currently in development for the treatment of invasive fungal diseases, including Aspergillus species. A recent single-arm, open-label, phase 2b study evaluated olorofim for the treatment of invasive fungal diseases in patients with few or no therapeutic options and showed efficacy and good tolerability.

Rezafungin is a licenced antifungal agent for the treatment of invasive candidiasis. While clinical data on rezafungin to treat Candidozyma auris is currently very limited, it may emerge as a viable option in future clinical trials.

Influenza therapeutics: progress and persistent gaps

While multidrug-resistant fungal pathogens represent an emerging challenge for hospital clinicians, respiratory viruses continue to pose a parallel threat, driving seasonal surges in hospitalisation and mortality each winter. This was described by Dr Anika Singanayagam, consultant virologist at the UKHSA and senior clinical research fellow at Imperial College London, during her BSAC session at the BSAC New Agents Conference.

In England, modelling by the UKHSA estimated approximately 7,800 influenza-attributable deaths during the 2024/25 winter season.

Yet despite this burden, therapeutic options remain relatively limited. Dr Singanayagam described how oseltamivir continues to be the mainstay of antiviral therapy, with inhaled or intravenous zanamivir reserved for selected cases. She reiterated the importance of early treatment with these agents.

More recently, the endonuclease inhibitor baloxavir has been licenced in the UK but has not been submitted to the National Institute for Health and Care Excellence for technology appraisal.

For clinicians concerned with treating influenza in hospital,  the UKHSA has recently updated its comprehensive guidance on the use of antiviral agents for the treatment and prophylaxis of seasonal influenza.

Despite the substantial global burden of severe influenza, there remains a notable lack of antiviral treatments specifically approved for hospitalised patients with severe disease.

Most licensed antivirals have been mostly studied in outpatient populations with uncomplicated influenza. Consequently, evidence supporting their effectiveness in patients admitted to hospital with severe influenza remains limited.

Platform trials for antiviral therapeutics

Given the higher mortality associated with severe influenza, the absence of robust clinical trial evidence specifically addressing hospitalised patients represents a substantial unmet patient need.

Large adaptive platform trials may help to close these evidence gaps. The REMAP-CAP and RECOVERY trials have demonstrated how multiple therapeutic strategies can be evaluated simultaneously in critically ill patients with severe respiratory infections, including influenza.

Building on their success in identifying effective Covid-19 therapies, both trial platforms are now evaluating antiviral and immunomodulatory approaches for the treatment of severe influenza.

Alongside these trial innovations, several antiviral agents are progressing through clinical development, as described by Dr Singanayagam in her BSAC session.

One example is CD388, a first-in-class, long-acting, drug-Fc conjugate composing multivalent dimers of the neuraminidase inhibitor zanamivir, linked to the Fc component of human immunoglobulin G1.

It is currently at the phase 3 clinical trial stage of investigation, following a phase 2a randomised human challenge study.

Healthy participants received a single subcutaneous dose of CD388 before intranasal influenza challenge. Compared with placebo, CD388 significantly reduced viral load exposure, peak viral load and the rate of laboratory-confirmed infection.

Symptom scores were also lower, and the treatment was well tolerated, with few adverse events. Larger trials are now needed to confirm its preventive efficacy against influenza.

Evolution of preventative strategies for RSV

Respiratory syncytial virus (RSV) remains another major cause of viral disease-driven hospitalisation, particularly among infants and older adults. Almost all children are infected with RSV within the first two years of life, and hospitalisation rates are highest during early infancy.

Commenting on the treatment landscape for RSV at the BSAC New Agents Conference, Dr Singanayagam noted that ‘there are really quite limited existing therapeutics’, similar to influenza.

The inhaled antiviral ribavirin is an option but is reserved for the sickest patients and there are concerns regarding toxicity and modest clinical efficacy, she explained.

In contrast, preventive strategies are advancing. Vaccination programmes targeting both infants and older adults have been rolled out across the UK, with varying levels of vaccine uptake, but a generally positive impact on hospitalisation rates.

The monoclonal antibody nirsevimab is also being rolled out across the UK. Single dose nirsevimab is set to replace the monthly palivizumab injections previously used in a limited number of vulnerable infants.

While palivizumab offers roughly 55% protection, clinical trial data suggest nirsevimab exceeds 80% effectiveness. It will also be administered seasonally to infants and young children at high-risk due to comorbidities.

Concerningly, Dr Singanayagam highlighted possible resistance to nirsevimab on the horizon, as reported by a recent French study.

Conclusion

Reflecting on the BSAC New Agents Conference, the question is not simply about which new therapies are available, but how they can be used judiciously within multidisciplinary care.

Surveillance, therapeutics and infection prevention strategies must increasingly work together in the fight against emerging infectious diseases.

As the pace of scientific progress accelerates, translating these advances into everyday clinical practice will be critical to improving patient outcomes and maintaining the effectiveness of the interventions that are also beginning to emerge.