Prehospital Administration of Antibiotics for Patients with Suspected Severe Infection: A Systematic Review and Meta Analysis

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Background: Sepsis is a time-sensitive, serious condition; therefore, early recognition and prompt initiation of therapy are critical to improving outcomes in patients with infection. We sought to evaluate whether prehospital antibiotic administration (PHAA) is associated with improved outcomes in patients with suspected severe sepsis. Methods: We conducted a systematic review and meta-analysis. This review was conducted in accordance with the PRISMA guidelines, and the protocol was developed a priori and registered with the International Prospective Register of Systematic Reviews (PROSPERO). PubMed, Embase, Cochrane, and Scopus were searched from inception through January 2026. Randomized controlled trials (RCTs) and observational studies evaluating empirical PHAA compared with the standard of care were included. The risk of bias and certainty of evidence were assessed. Outcomes included short- and long-term mortality, hospital length of stay (HLOS), and intensive care unit (ICU) admission. Sensitivity analyses were performed. Results: Eleven studies recruiting 23,146 patients were included (three RCTs and eight observational studies). Restricting the short-term mortality analysis to RCTs alone showed no mortality benefit with PHAA (RR 0.96, 95% CI 0.74–1.23), whereas the broader, observational-dominated pooled analysis suggested a possible reduction in short-term mortality (RR 0.84, 95% CI 0.68–1.02, I2 = 51.0%), reaching statistical significance when restricted to the adult sepsis/septic shock population (RR 0.82, 95% CI 0.69–0.99, I2 = 18.5%). No significant difference in short-term mortality was observed in the exploratory subgroup analysis of two high-severity studies (RR 0.89, 95% CI 0.67–1.18). There were no significant long-term mortality differences in the observational and RCT studies (RR 0.86, 95% CI 0.71–1.04 and RR 1.09, 95% CI 0.76–1.54, respectively). Patients who received PHAA had no significantly different ICU admissions (RR 1.12, 95% CI 0.95–1.33) or HLOS (MD −1.79 days, 95% CI −6.05 to 2.47). Even though individual studies showed no significant difference, pooled HLOS was significantly higher with PHAA for the RCT subgroup (MD 0.66, 95% CI 0.42–0.90, I2 = 0.00%) after conversion of median to mean values (for better statistical compatibility). Conclusions: PHAA was not associated with a significant reduction in short-term mortality, though a significant reduction was observed when restricted to adult sepsis/septic shock population. No mortality benefit was found in pooled RCTs, mixed-age population studies, or long-term mortality. Observational studies suggest a possible mortality benefit, whereas randomized evidence does not confirm it. This discrepancy may reflect confounding by indication, patient selection, severity, and differences in EMS systems rather than a true treatment effect. The certainty of evidence remains very low, and data on prehospital antibiotic type, blood culture, and infection severity are lacking. Therefore, high-quality prospective RCTs are warranted.

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