Inflammatory biomarker-based clinical practice in patients with pneumonia: A systematic review of randomized controlled trials

Abstract Objectives: Biomarker-based clinical practice is currently gaining ground and increasingly affects decision making. A variety of biomarkers have been studied through the years and some of them have already an established role in modern medicine, such as procalcitonin (PCT) which has been proposed to reduce antibiotic exposure. We purposed to systematically review all biomarkers examined for guiding the clinical practice in patients with pneumonia. Methods: A systematic review on PubMed was performed on April 2023 by two independent researchers using the PRISMA guidelines. Randomized trials which enrolled patients with pneumonia and compared biomarker-guided strategies to standard of care were included. Results: 1242 studies were recorded, from whom 16 were eligible for this study. 14 studies investigated PCT as a biomarker. From these, 8 studies reported on community acquired pneumonia (CAP), 2 on ventilator associated pneumonia (VAP), 1 on aspiration pneumonia, 1 on hospital acquired pneumonia (HAP) and 2 on exacerbation of chronic obstructive pulmonary disease (ECOPD). There was 1 study, referred to VAP, that investigated interleukin-1β (IL-1β) and interleukin-8 (IL-8) and 1 study that reported the role of C-reactive protein (CRP) in ECOPD. In a total of 4751 patients in 15 studies, the biomarker-based approach did not lead to increased mortality [OR: 0.998 (95%CI: 0.74-1.34, p value: 0.991). I2:19%]. Among different types of pneumonia and time-points of assessment, biomarker-guided practice appeared to improve antibiotic-related outcomes, such as rate of antibiotic prescription, duration of antibiotic therapy and rate of antibiotic exposure, while 5 studies reported a possible decrease in antibiotic-related adverse effects. Biomarker-guided practice did not seem to lead in an increase in other adverse outcomes such as need for hospitalization and duration of hospitalization. However, the included studies have high risk of bias mainly due to improper blinding of participants/personnel and outcome assessors. Conclusion: Biomarker-guided clinical practice improves provided healthcare, in terms of reduced antibiotic consumption with no inferiority to mortality, relapses and exacerbations in patients with different types of pneumonia. Thus, such approaches should be further evaluated to achieve personalized medicine.