Antimicrobial resistance (AMR) is a growing global health challenge associated with nearly five million deaths globally each year. The widespread use of antibiotics without confirmed bacterial infection is a critical driver of AMR—a problem that better diagnostics could help solve. We propose a new approach to this challenge: using an advance market commitment (AMC) to incentivize the development of rapid diagnostic tests. Our focus? Neonatal sepsis in low- and middle-income countries (LMICs), where some newborns receive antibiotics that they do not need, while many others miss out on treatment because current diagnostic tests are too slow to guide initial treatment decisions.

Antimicrobial resistance and the role of diagnostics

Diagnostics play an essential role in tackling AMR by enabling accurate and timely treatment and reducing unnecessary antibiotic use. However, diagnostics currently receive less than 8 percent of AMR research and development investment. Moreover, there have been few efforts to coordinate diagnostic development or allocate resources efficiently toward those diagnostics that could yield the greatest benefit in controlling AMR.

Given this gap, we considered four factors to help us identify the most promising area for the development and deployment of diagnostics: the scale of the problem, unmet need, implementability, and diagnostic impact. These factors are partly based on both the REASSURED criteria for diagnostics in resource-limited settings and the STEDI framework, and World Health Organization (WHO) Priority Pathogen List, which have helped direct global attention and investment on antibiotic development that addresses the most urgent public health needs.

These four factors led us to prioritize a rapid triage diagnostic test that helps rule in or rule out neonatal sepsis as a priority candidate for greater investment.

Why is a rapid diagnostic for neonatal sepsis an AMR priority?

Neonatal sepsis is a systemic, often life-threatening infection in newborn infants in the first 60 to 90 days of life. Untreated, it has a mortality rate of 30 percent, based on several research studies (see 1, 2 and 3).

The scale of the problem

• Disease burden: Globally, infections cause nearly a quarter (23 percent) of all neonatal deaths. Neonatal sepsis is estimated to affect 1.3 to 3.9 million neonates and account for 400,000 to 700,000 annual deaths. Ninety-nine percent of these deaths occur in LMICs, especially in sub-Saharan Africa and Asia.
• Resistance burden: Over 30 percent of neonatal sepsis deaths are attributable to resistant pathogens, which are more difficult to treat. Recent studies in India and other countries found alarming rates of resistance of over 50 to 70 percent to first-line antibiotics. Although the burden of resistant infections is high and rising across various infectious syndromes, it is particularly pronounced in bloodstream infections (sepsis), especially among neonates, compared to other conditions, such as urinary tract infections, meningitis, or upper respiratory tract infections.

Unmet need

• Innovation gap: There is no widely adopted, effective point-of-care test for neonatal sepsis. While treatable with antibiotics if identified early, current diagnostic methods—which take 48 to 72 hours—cannot guide crucial and life-saving initial treatment decisions. As a result, doctors have to rely on their clinical judgement on whether to initiate diagnostics. This leads to both preventable deaths from missed diagnoses and unnecessary antibiotic use that drives AMR. A rapid diagnostic would save lives by reducing the number of missed cases. It would also spare babies from antibiotic use when not needed, which would help slow resistance and avoid adverse health outcomes from early life exposure to antibiotics.
• Market failure: As discussed in more depth in our next post, the commercial incentives to develop and deploy such a diagnostic are inadequate compared to their social value.

Implementability

• Scientific feasibility: Rapid diagnostics for neonatal sepsis are likely technologically feasible, based on current research and development pipelines; this includes biomarker-based approaches, molecular diagnostics, metagenomic techniques, machine learning, and AI technologies, as well as other novel approaches. Although there are technical challenges—such as with blood volumes (and therefore bacterial load) in neonates, and in designing a test that is fit for use in resource-constrained settings—a rapid diagnostic is likely more feasible compared to other potentially more ambitious diagnostic targets, such as a blood culture independent diagnostics for antimicrobial sensitivity and resistance testing.
• Alignment with global and local policy priorities: Rapid diagnostics are also a well-established area of clinical need; the WHO have focused on the need for neonatal sepsis diagnostics, and physicians and healthcare workers throughout LMICs have underscored the importance of rapid diagnostics in reducing neonatal mortality to prevent the further escalation of AMR.

Diagnostic impact

• Influence on antibiotic use: A rapid diagnostic for neonatal sepsis is likely to influence prescription behavior and antibiotic use because antibiotics to treat sepsis are typically administered at primary healthcare facilities and above, as opposed to an outpatient setting. Such facilities have greater access to healthcare workers and established protocols for investigating and treating diseases, which means that a new diagnostic test is more likely to be used and integrated into existing protocols for diagnosis and management of neonatal sepsis. This is likely less true of diagnostics used in outpatient settings where oral antibiotics are cheap and may be used more liberally (a rapid diagnostic to distinguish bacterial and viral respiratory tract infection in the community may therefore have less effect on antibiotic use).
• Adoption potential: The relative affordability and ability to use a rapid diagnostic in resource-constrained settings with limited laboratory capacity have led organizations, such as FIND, UNICEF, and WHO, to prioritize this technology.

Advancing diagnostic investment on neonatal sepsis

The above factors—the scale of the problem, unmet need, implementability, and diagnostic impact—led us to prioritize neonatal sepsis as a candidate for greater diagnostic investment. The working group and its partners will integrate these considerations into a comprehensive cost-effectiveness analysis—our preliminary analysis suggests a diagnostic test would be highly cost-effective, saving lives and reducing unnecessary antibiotic prescriptions.

Read our next blog, where we detail why the commercial incentives to develop and deploy a diagnostic for neonatal sepsis are inadequate compared to their social value.