The Comeback Infection: How Scientists Are Racing against C. difficile

Dr. Michael Perry first began tracking Clostridioides difficile (CDI) in Wales. Years of declining infection rates had brought cautious optimism to microbiology labs and infection prevention and control (IPC) teams across the United Kingdom (UK). But by 2024, the tide had turned again, and fast. Wales saw +69%¹ (2024/25 vs 2020/21) of CDI rates, while England is shown separately at +49,8%¹, a reminder that this pathogen has never gone quietly.

Few people understand that shift better than Dr. Michael Perry, Consultant Clinical Scientist at Public Health Wales Microbiology and Head of the UK Anaerobe Reference Unit.

A Pathogen That Refuses to Disappear

C. difficile has always been hard to contain. Its spores persist in the environment and resist many commonly used cleaning products. Hypervirulent strains such as RT027 and RT078 have already caused global disruption, but now a new ribotypes¹, like RT955, are emerging with concerning traits, including reduced metronidazole susceptibility and reports of severe outcomes in recent outbreaks under investigation.

Even more worrying is where infections are appearing.

Data show an uptick in community‑onset cases, reinforcing concerns that CDI transmission is not limited to hospital settings alone.

When Testing Isn’t Simple

European and UK guidelines now recommend multistep approaches, using Glutamate Dehydrogenase (GDH) screening, toxin assays, and Nucleic Acid Amplification Test (NAAT), but even these are not foolproof. Large audits covering more than 255 000 GDH/NAAT results revealed that some GDH assays have been reported to produce false positives, including cross‑reactivity with S. aureus, highlighting the importance of assay selection. NAATs, while highly sensitive, detect both true infections and asymptomatic carriers, demanding careful clinical interpretation. CDI remains, at its core, a clinical diagnosis.

Yet, despite these challenges, the diagnostic landscape is shifting. Ultra‑sensitive toxin assays may refine accuracy further, and laboratories across the UK are upgrading algorithms to close gaps that once allowed outbreaks to go unnoticed.

Genomics: The Turning Point

While traditional diagnostics struggle, genomics is providing answers. Wales now performs Next Generation Sequencing (NGS) typing on more than 90%¹ of PCR/GDH positive isolates, giving clinicians and infection control teams unprecedented clarity.

NGS can distinguish genuine transmission from pseudo-outbreaks; supporting more targeted infection prevention decisions or misplaced interventions. It identifies resistance genes, tracks virulence factors, and maps how strains spread within and between healthcare facilities.

The UK Anaerobe Reference Unit, led by Dr. Perry, supports hospitals with rapid strain characterization and susceptibility testing. New tools like Xpert® C. difficile BT even allow early presumptive detection of RT955, giving hospitals valuable time to isolate, contain, and act.

The Future for CDI Control

Behind every lab result is a patient, and behind every outbreak response is a team balancing science, operational pressures, and the realities of care. The resurgence of CDI has reinforced the need for tighter diagnostic algorithms and patient-centred management pathways that support both clinicians and families.

For Dr. Michael Perry, one message is clear: the battle against CDI is far from over, but with smarter testing, faster sequencing, and stronger collaboration, healthcare systems now have the tools to stay ahead of this constantly shifting threat.