Background : Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. Methods : In LEAP 1, adults (Pneumonia Outcomes Research Team [PORT] risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 hours (q12h; 5‒7 days) or moxifloxacin 400 mg every 24 hours (q24h; 7 days), with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h (5 days) or moxifloxacin 400 mg q24h (7 days). Primary outcomes were early clinical response (ECR) 96±24 hours after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen test, serology, and/or real-time PCR). Results : Baseline CABP pathogens were detected in 709/1289 patients (55.0% [microbiological intent-to-treat population]). The most frequently identified pathogens in this population were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. Conclusions : Lefamulin is a valuable IV and oral monotherapy option for empiric and directed CABP treatment in adults.