Abstract
BACKGROUND: Pneumonia is a leading cause of ICU admission and mortality, requiring prompt and adequate antimicrobial therapy to improve outcomes. Conventional cultures are slow and often insensitive, delaying targeted treatment. Syndromic PCR panels offer rapid identification of pathogens and resistance genes directly from respiratory samples, potentially improving early antibiotic optimization. However, the true clinical benefit of these diagnostics in critically ill patients remains uncertain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PCR-based molecular diagnostics with standard culture techniques in predominantly adult ICU patients with severe community-acquired, hospital-acquired, or ventilator-associated pneumonia. Literature searches were performed in PubMed, Embase, and Cochrane CENTRAL from inception to July 16, 2025. The primary outcome was in-hospital mortality. Secondary outcomes included adequacy of initial antimicrobial therapy and time to effective antibiotic administration. Data were synthesized using random-effects models. RESULTS: We included five randomized controlled trials comprising 2,466 patients. Syndromic PCR testing did not significantly reduce in-hospital mortality, the primary outcome (RR 1.04; 95% CI: 0.90–1.21; p = 0.57; I² = 0%). However, PCR testing was associated with a higher rate of adequate initial antimicrobial therapy (RR 1.82; 95% CI: 1.10–3.00; p = 0.02; I² = 97%) and a reduction in time to effective antibiotic administration (mean difference − 27.98 h; 95% CI: − 46.07 to − 9.89; p = 0.002; I² = 94%). CONCLUSIONS: Syndromic PCR diagnostics did not reduce in-hospital mortality in critically ill patients with pneumonia but were associated with improved adequacy of initial antimicrobial therapy and faster initiation of effective treatment. These findings support their role as a complementary tool in ICU-based antimicrobial stewardship. TRIAL REGISTRATION: PROSPERO CRD420251006301. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-025-05623-0.