Clinical outcomes of empirical antibiotic strategies in community-acquired pneumonia-associated sepsis: a propensity score-matched cohort study

Background Community-acquired pneumonia (CAP) complicated by sepsis remains a life-threatening infectious syndrome associated with substantial morbidity, mortality, and healthcare burden. Although β-lactam-based combination therapy is widely recommended for severe CAP, the optimal empirical antibiotic strategy for septic pneumonia remains uncertain. At the same time, empirical antibiotic selection must balance adequate early treatment against unnecessary broad-spectrum antibiotic use and the risk of antimicrobial resistance. Evidence specifically targeting this high-risk population is limited. This study aimed to compare the clinical outcomes of β-lactam monotherapy and β-lactam-based combination therapy in patients with CAP-associated sepsis. Methods We conducted a retrospective cohort study at Zhejiang Xiaoshan Hospital from January 2021 to January 2025, including adult patients with CAP-associated sepsis who received empirical β-lactam monotherapy or β-lactam-based combination therapy with macrolides or doxycycline within 48 hours of admission. A total of 100 patients were included before propensity score matching, and 80 patients remained after 1:1 matching. The primary outcome was time to clinical stability (TTCS). Secondary outcomes included mortality, length of hospital stay, antibiotic duration, changes in SOFA score, inflammatory biomarkers, clinical cure, and adverse events. TTCS was analyzed using Kaplan–Meier analysis and Cox proportional hazards regression. Results Median TTCS was 5.0 days with monotherapy and 4.0 days with combination therapy (P = 0.129). Combination therapy also showed favorable trends in hospitalization duration, clinical cure, inflammatory marker reduction, and organ function recovery. After adjustment for admission SOFA score, combination therapy showed a nonsignificant trend toward earlier clinical stability (adjusted HR 1.42, 95% CI 0.88–2.29; P = 0.151). No significant increase in adverse events was observed. Conclusions In patients with CAP-associated sepsis, β-lactam-based combination therapy showed a trend toward earlier clinical stability than β-lactam monotherapy, although the difference was not statistically significant. This study addresses an important evidence gap in septic pneumonia management and supports further investigation of individualized antimicrobial strategies guided by disease severity and biological characteristics. The retrospective single-center design and relatively small sample size should be considered when interpreting these findings.