Procalcitonin and lung ultrasonography based antibiotherapy in patients with lower respiratory tract infection in Swiss emergency departments: stepped-wedge cluster-randomized trial

Background

Community-acquired lower respiratory tract infections (LRTI) are one of the most common motivations for emergency department (ED) consultations and stands as the leading cause of inappropriate antibiotic prescription. Besides the side effects, antibiotic overuse alters the microbiome and generates antibiotic resistance. When assessing patients with LRTIs, the challenge for ED physicians is to identify those with community-acquired pneumonia (CAP) of bacterial origin, who will most likely benefit from antibiotics. The low diagnostic accuracy of existing tools, as well as the poor adherence of clinicians to test guidance are leading causes of inappropriate antibiotic use.

Several diagnostic tests can assist in identifying patients with LRTI who require antibiotics. Clinical prediction score can refine the probability of CAP. Lung ultrasound (LUS) has a better diagnostic performance than chest X-ray, the historic reference imaging modality to consolidation in ED. LUS is performed quickly at the bedside without radiation. Procalcitonin (PCT), a host inflammatory biomarker, can be used safely to guide antibiotics, while its impact on prescription is controversial. None of these tools on its own is sufficient to optimise antibiotic prescription, while a combined approach could better guide clinicians.

A trial by the applicant previously evaluated an algorithm sequentially combining PCT and LUS (LUS performed only in patients with elevated PCT) to manage patients with LRTIs in primary care (SNSF 407240_167133/1). PCT led to a 26% absolute reduction in 28-day antibiotics compared with usual care, without affecting clinical outcome. As only 8% of patients had an elevated PCT, LUS was rarely performed and did not further reduce antibiotic prescription. 

Rationale

The prevalence of CAP is higher in ED patients with LRTI and they are more likely to benefit from antibiotics than patients in primary care. We propose to evaluate the use of a diagnostic algorithm adapted to the ED as the summative value of LUS with PCT remains unknown in this setting.

Goal

To promote simple decision support tools to mitigate antimicrobial resistance and improve health outcomes.

Objective

To decrease the proportion of patients prescribed an antibiotic without increasing the risk of treatment failure.

Methodology

Multicenter stepped-wedge cluster-randomized trial. Following a baseline period during which all centers are in the control group (usual care), one centre will be randomized to roll into the intervention every period during the 2 year-study. 

Study population and setting

Adults presenting to 9 Swiss EDs for a LRTI are screened. They are included if they present a focal auscultation finding or an abnormal vital sign. Patients on antibiotics for the current episode, hospitalized in the previous 14 days, with a severe underlying lung disease, severe immunosuppression, pregnancy or clinical instability requiring intensive care unit are excluded.

Intervention

The PLUS clinical management algorithm combines the results of a pneumonia clinical prediction score (which refines the pre-test probability of CAP), LUS and, according to its pneumonia post-test probability, PCT to identify patients who will most likely benefit from antibiotics. 

LUS is performed in all patients. PCT is only measured in patients with lung consolidation on LUS and in those with a high clinical probability of pneumonia (high post-LUS residual probability of CAP) despite negative LUS. Antibiotics are only recommended to patients with elevated PCT (=0.25 µg/L). A clinical severity score will ensure the safety of the intervention in those with discordant results (LUS consolidation and low PCT).

Follow-up PCT is repeated after 6-24 hours in admitted patients who did not receive antibiotics and in those in whom the algorithm was overruled. Patients discharged home without antibiotics have a phone evaluation after 48 hours.

Phone follow-up on day 7, 28 and 90.