Procalcitonin evaluation of antibiotic use in COVID-19 hospitalised patients: The PEACH mixed methods study

Background

Early in the COVID-19 pandemic, there was concern about potentially unnecessary antibiotic prescribing in the National Health Service. Procalcitonin testing was being used in some hospitals to guide antibiotic use. This study aimed to investigate the impact of procalcitonin testing on United Kingdom’s antibiotic prescribing and health outcomes.

Methods

Mixed-methods study comprising quantitative, qualitative and health economic work packages, including a:

1. survey of National Health Service hospitals to understand procalcitonin use

2. retrospective, controlled, interrupted time series analysis of aggregated, organisation-level data, including antibiotic dispensing, hospital activity and procalcitonin testing from acute hospital trusts/hospitals in England/Wales. Primary outcome: change in level and/or trend of antibiotic prescribing rates following introduction of procalcitonin

3. multicentre, retrospective, cohort study of 5960 patients using patient-level clinical data from 11 trusts/health boards to determine the difference in early antibiotic prescribing between COVID-19 patients who did/did not have baseline procalcitonin testing by using propensity score matching. Primary outcome: days of early antibiotic therapy

4. qualitative study exploring the decision-making process around antibiotic use for inpatients with COVID-19 pneumonia to identify the contextual factors, feasibility and acceptability of procalcitonin testing algorithms

5. health economic analysis evaluating the cost-effectiveness of baseline procalcitonin testing using the matched data within a decision-analytic model.

Setting

Acute hospital trusts/health boards in England/Wales.

Participants

Inpatients ≥ 16 years, admitted to participating trusts/health boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020, National Health Service healthcare workers.

Results

Early in the COVID-19 pandemic, procalcitonin use was expanded/introduced in many National Health Service hospitals, with variation in guidance and interpretation of results. The number of hospitals using procalcitonin in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%), and its use in intensive care unit increased from 70 (47.6%) to 124/147 (84.4%). Introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in antibiotic use, which was not sustained. Patient-level data showed that baseline procalcitonin testing was associated with an average reduction in early antibiotic prescribing of 0.43 days (95% confidence interval: 0.22 to 0.64 days, p < 0.001) and a reduction of 0.72 days (95% confidence interval: 0.06 to 1.38 days, p = 0.03) in total antibiotic prescribing, with no increased mortality/hospital length of stay. Interviews revealed concerns about secondary bacterial infections that led to increased antibiotic prescribing in COVID-19 patients. As experience increased, clinician’s ability to distinguish between COVID-19 alone and bacterial coinfections increased. Antibiotic prescribing decisions were influenced by factors such as senior support, situational factors and organisational influences. The health economic analysis concluded that baseline procalcitonin testing was more likely to be cost-effective than not, albeit with some uncertainty.

Conclusion

Baseline procalcitonin testing appears to have been an effective antimicrobial stewardship tool during the first wave of the pandemic, reducing antibiotic prescribing without evidence of harm.

Limitations

The retrospective, hospital record-based studies were limited by missing data, incorrectly recorded information and lack of randomisation. Interviews with clinicians were conducted more than a year after the first wave, potentially resulting in recall bias.

Future work

This study highlights the need for adaptive, inclusive, wide-reaching trials of infection diagnostics and implementation research to assess clinical utility before routine introduction into clinical practice.

Funding

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132254.