Efficacy and safety of Omadacycline in community-acquired pneumonia among elderly patients: a real-world evidence study

Objective This study aimed to evaluate real-world effectiveness and safety of omadacycline for elderly community-acquired pneumonia (CAP) versus tigecycline, moxifloxacin, and cefoperazone-sulbactam after inverse probability of treatment weighting (IPTW). Methods This single-center retrospective cohort study enrolled non-ICU hospitalized elderly CAP patients. Missing covariates were handled by multiple imputation, and IPTW balanced groups. Primary outcome was pragmatic clinical response (improvement in at least one of laboratory markers, chest imaging, or clinical symptoms), with a sensitivity analysis requiring all three. Secondary outcomes included hospital stay, antibiotic duration, microbiological clearance, and adverse events. Subgroup analyses used age < 75 vs ≥ 75 years and CURB-65 < 2 vs ≥ 2. Results A total of 1,208 patients were included: 177 in the omadacycline group, 124 in the tigecycline group, 666 in the moxifloxacin group, and 241 in the cefoperazone-sulbactam group. After IPTW adjustment, omadacycline showed a pragmatic clinical response comparable to tigecycline, higher than moxifloxacin, but lower than cefoperazone-sulbactam. Omadacycline was associated with shorter hospital stay than tigecycline and cefoperazone-sulbactam, but longer than moxifloxacin; antibiotic duration was comparable to tigecycline, shorter than cefoperazone-sulbactam, but longer than moxifloxacin. Microbiological clearance was lower with omadacycline in the evaluable subset, whereas recorded adverse events were fewer but limited by rare-event sparsity. Exploratory subgroup analyses suggested that cefoperazone-sulbactam had a higher response than omadacycline in patients aged <75 years or with CURB-65 <2. Subgroup analyses suggested heterogeneous associations by age and disease severity and should be interpreted as exploratory. Conclusion In this real-world analysis of elderly patients with CAP after IPTW adjustment, omadacycline showed a pragmatic clinical response comparable to tigecycline, higher than moxifloxacin, but lower than cefoperazone-sulbactam. Omadacycline was associated with shorter hospital stay than tigecycline and cefoperazone-sulbactam, but longer hospital stay than moxifloxacin. Antibiotic duration was comparable to tigecycline, shorter than cefoperazone-sulbactam, but longer than moxifloxacin. Given the broad pragmatic endpoint, high baseline response rate, sensitivity to endpoint definition and missing-data handling, incomplete microbiological follow-up, and residual confounding inherent to retrospective data, these findings should be interpreted as exploratory and require prospective validation.