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<h3>Background and Importance</h3> Lower respiratory tract infections are a leading cause of hospitalisation and antibiotic use, contributing to antimicrobial resistance and healthcare burden. Unlike conventional microbiological cultures that are often slow and less sensitive, PCR-based diagnostics enable rapid and highly sensitive detection of pathogens and resistance genes. When implemented within a pharmacist-led molecular diagnostics laboratory where results are interpreted collaboratively within a multidisciplinary team, these methods enable prompt, targeted antimicrobial optimisation and improved clinical outcomes <h3>Aim and Objectives</h3> To assess the value of pharmacist-interpreted PCR compared with conventional culture in optimising antibiotic therapy and improving laboratory outcomes in patients with lower respiratory tract infections. <h3>Material and Methods</h3> A retrospective observational study was conducted at the University Clinic of Pulmonology and Allergology, including 74 hospitalised adults (>18 years) with clinical signs of lower respiratory tract infection. Respiratory samples (sputum, bronchoalveolar lavage, and blood cultures) were analysed using both the BioFire FilmArray Pneumonia Panel Plus and conventional microbiological culture. Patient data, including infection biomarkers (C-reactive protein (CRP) and leukocytes) and length of hospital stay (LOS), were extracted from electronic medical records. <h3>Results</h3> PCR demonstrated higher diagnostic sensitivity than conventional culture, identifying 66 pathogens compared with 10 isolates. Pharmacist interpretation of PCR findings resulted in 18 antibiotic de-escalations and nine escalations, while culture-based results led to only two de-escalations and two escalations. At admission, median biomarker levels were leukocytes 12.43 (3.37–26.72) and CRP 37.70 (3.00–144.90). Following pharmacist-guided optimisation of therapy based on PCR results, these values improved to leukocytes 11.45 (5.49–19.15) and CRP 3.00 (1.50–63.40). The median LOS was 11 days (6–25). Patients positive for Human Rhinovirus, especially those with viral–bacterial co-infections, showed the strongest correlation with longer LOS (p<0.001). Five patients who were negative for Human Rhinovirus/Enterovirus + bacteria on culture were identified as positive using PCR, underscoring its superior clinical relevance and the opportunity for early pharmacist-led therapeutic management. <h3>Conclusion and Relevance</h3> Pharmacist-led PCR molecular diagnostics and result interpretation facilitate timely, evidence-based optimisation of antimicrobial therapy in patients with lower respiratory tract infections, strengthen antimicrobial stewardship efforts, enhance multidisciplinary teamwork, and lead to improvements in clinical outcomes. <h3>Conflict of Interest</h3> No conflict of interest