This week saw the publication in the Lancet Global Health of an important trial conducted in Thailand and Myanmar, with the objective of exploring whether C-reactive protein (CRP) testing at the point-of-care could rationalise antibiotic prescription in primary health care settings (1). A reduction of 5% was recorded between the intervention and control group. We share reflections on the study and its findings below, cautioning that to truly change the shape of prescribing would require accompanying measures beyond these devices, and that the cost of deploying such a package requires consideration in comparison with other measures that might reduce antibiotic prescribing.

As the burden of antimicrobial resistance increases, the number of prescriptions for antibiotics in developing countries continues to grow. Adequate diagnostics for serious bacterial infections are lacking, leading to a “covering all bases” approach by healthcare workers. Antimicrobial stewardship programmes are now being asked to consider the use of point-of-care (POC) biomarker testing to assist in detection of patients with serious bacterial infections.

The CRP trial in Thailand and Myanmar was a multicentre, open-label, randomised, controlled trial in febrile participants aged at least 1 year. Individuals were randomly assigned at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B). Health-care providers were blinded to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. 2410 patients were recruited in total (CRP group A n=803, CRP group B n=800 and control group n=807).

This data has been interpreted by the group as follows: “in febrile patients attending primary care in these settings, testing for CRP at point of care with a threshold of 40 mg/L resulted in a modest but significant reduction in antibiotic prescribing”. Additionally, they found that “patients with high CRP were more likely to be prescribed an antibiotic, with no evidence of a difference in clinical outcomes”. However, it is worth mentioning only a modest risk reduction of 5% between the intervention group (34%) and control group (39%) was found. It is interesting here to raise the question of what an ideal or target level of antibiotic prescribing would be in these contexts; supposing a larger reduction is required in order to address antimicrobial resistance, then it would be valuable to learn whether alternative or additional interventions could more cost-effectively achieve safe reductions in use.

In her commentary on the paper, Kristina Keitel also notes that “The results from this study again emphasise that effective interventions to reduce antibiotic use cannot rely on the introduction of a single diagnostic test. In addition to clinical guidance, provider training, patient education, supervision, and policy strategies have an important role” (2).

A social sciences study accompanying this trial investigated the social role of CRP POCT through its interactions with healthcare workers and patients as well as the existing patient-health system linkages that might interact with CRP POCT (3). This study found positive attitudes towards the test among patients and healthcare workers. Patients opinions were affected by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis. Healthcare workers thought that the test aided their negotiations with patients, and additionally legitimised their ethical decisions in an increasingly restrictive antibiotic policy environment. The study later went on to hypothesise that “CRP POCT could entail greater patient adherence to antibiotic treatment, but it could also encourage riskier health behaviour and entail potentially adverse equity implications for patients across generations and socioeconomic strata”.

Overall, this trial presents useful information for informing strategies to target antibiotic use, and demands further research to ensure that investment in efforts to reduce antibiotic use are cost-effective and do not have further repercussions through unintended consequences.

References

1) Althaus T, Greer RC, Swe MMM et al.

Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial.

Lancet Glob Health. 2019; 7: e119-e131

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(18)30444-3/fulltext

2) Kristina Keitel

Biomarkers to improve rational antibiotic use in low-resource settings.

Lancet Glob Health. 2019

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(18)30497-2/fulltext

3) Marco J.Haenssgen, Nutcha Charoenboon, Thomas Althaus, Rachel C.Greer, Daranee Intralawan , Yoel, Lubell.

The social role of C-reactive protein point-of-care testing to guide antibiotic prescription in Northern Thailand.

Social Science and Medicine. 2018; 202.

https://www.sciencedirect.com/science/article/pii/S0277953618300741