Sepsis and Superbugs: Two Edges of the Same Sword

Sepsis is a critical global healthcare challenge, marked by complex and rapidly evolving symptoms, which can escalate with alarming speed leading to multi-organ failure. This leaves only a narrow window for effective intervention. Mortality rates are high, approaching 30% in both acute and post-acute phases, and treatment options are still severely limited.

While not every instance of sepsis is caused by an infection, the majority happen when the body’s immune system overreacts to a pathogen. However, in almost a third of sepsis patients, doctors can’t find the specific pathogen causing the problem, which makes it hard to choose the right treatment

When a pathogen is identified, it is often among the “usual suspects” such as Klebsiella pneumoniae, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA). Less common viral or fungal causes present additional challenges, as their diagnosis is slower and treatment options are narrower. Many bacterial, viral and fungal pathogens frequently display alarming levels of drug resistance that complicates and lengthens the care pathway. 

Sepsis is an immediate and life-threatening emergency that demands swift clinical intervention. Time to treatment for sepsis is critical for a patient’s  survival; the longer it takes to give the first dose of antibiotics, the higher the risk of death. Doctors therefore need to treat the patient straightaway before they know what is causing the sepsis and what drugs will be effective. 

Most antimicrobial stewardship guidelines emphasize the need for rapid administration of broad-spectrum antibiotics in suspected sepsis. Once more is known, therapies may become more targeted. This creates an inherent tension: patients may initially not receive the most optimal therapy because the levels and types of drug resistance cannot be identified quickly enough; by the time treatment is adjusted, the delay can significantly increase the risk of death.

Could earlier detection ease the tension between rapid treatment and stewardship?

Clinicians are forced to walk a knife edge between delivering rapid, life-saving treatment and upholding antimicrobial stewardship to preserve effective antibiotics. Sepsis and AMR should be seen as two edges of the same sword. The two problems are intrinsically linked; yet fragmented information leaves a widespread lack of understanding within both healthcare systems and the general public.

Symptoms in sepsis are non-specific and diagnosis and treatment is further complicated by the intricate interplay between host responses and pathogen activity.  Standard laboratory methods, such as culture followed by antimicrobial susceptibility testing, are far too slow to inform the urgent treatment decisions required in sepsis. Timely identification of the pathogen and its resistance profile would not only guide treatment decisions but also facilitate appropriate antimicrobial stewardship.

A wide array of rapid diagnostic tools are now commercially available. However, there remains no “single test to rule them all” that can simultaneously identify multiple species and provide susceptibility data in one step. Whole-genome sequencing (WGS) is often heralded as the ultimate solution, delivering unparalleled resolution and, in many cases, actionable results within hours. Yet its widespread adoption is constrained by significant barriers, including the need for advanced bioinformatics expertise, substantial financial investment required, and new, end-to-end laboratory workflows.

The Challenge of Change: Why Adoption Isn’t Easy

Implementing changes, such as focussing on earlier diagnosis, within a healthcare system is complex and multifaceted, with numerous requirements and barriers to the adoption of novel diagnostic tools. 

A major hurdle is demonstrating and articulating the cost-benefit ratio of AMR diagnostics, particularly when many benefits are indirect or long-term. Hidden costs such as cancelled surgeries due to infection risk, the wider consequences of outbreaks caused by delayed treatment, and the sustained benefits of responsible antimicrobial stewardship are difficult to quantify.

Taking STRIDES to capture the full impact of AMR diagnostics

The Office of Health Economics (OHE) has recently developed a new value framework to highlight the benefits of diagnostics in combatting AMR. 

The OHE has introduced two new  values, into the STEDI framework ,  consolidating them into an expanded model known as the STRIDES framework:

• Spectrum value: Enables use of narrow-spectrum antibiotics by identifying specific pathogens and resistance patterns. 
• Transmission value: Reduces the spread of infectious and resistant pathogens through earlier detection and control.
• Research value: Supports the development of new antimicrobials by improving trial recruitment and design.
• Insurance value: Helps preserve last-line antimicrobials and mitigate catastrophic AMR outbreaks. 
• Diversity value: Facilitates more varied and targeted antimicrobial use, reducing resistance selection pressure. 
• Enablement value: Allows safe continuation of high-risk medical procedures by ruling in/out infections. 
• Surveillance value: Enables real-time, accurate monitoring of resistance trends

This new approach enables a more comprehensive and systematic evaluation of AMR diagnostics. Its goal is to better capture the factors that inform decision-making and reimbursement, ultimately supporting routine greater adoption of these tools in complex clinical scenarios such as sepsis.

The framework is still conceptual and requires more work to understand how it could be integrated within existing pathways, but serves to fill gaps in health technology assessments for AMR control tools.

Preventing Sepsis, Preserving Antibiotics

Sepsis requires rapid, life-saving treatment, while drug resistance silently undermines such treatment and drives poor outcomes. The solution lies, not in treating them as competing priorities, but addressing them together simultaneously rather than in isolation. 

Earlier pathogen detection, before sepsis fully develops, offers a critical opportunity to prevent deterioration while enabling clinicians to provide more targeted therapy and maintain antimicrobial stewardship. 

Achieving this will depend on wider adoption of rapid, reliable diagnostic tools that can inform decision-making in real time. Frameworks such as STRIDES are instrumental in evaluating these technologies and supporting their integration into practice, helping to bridge the gap between innovation and patient care. By recognizing sepsis and AMR as interconnected challenges, we can begin to align solutions that protect patients today while preserving effective treatments for the future.