来自利福霉素治疗社区获得性细菌性肺炎（LEAP）1 和 LEAP 2 期临床试验中利福霉素与莫西沙星比较的 pooled 微生物学发现和成人社区获得性细菌性肺炎的病原体的疗效结果。

Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin.

机构信息

Nabriva Therapeutics GmbH, Vienna, Austria.

Nabriva Therapeutics US, Inc., Fort Washington, PA, USA.

出版信息

J Glob Antimicrob Resist. 2022 Jun;29:434-443. doi: 10.1016/j.jgar.2021.10.021. Epub 2021 Nov 14.

DOI:10.1016/j.jgar.2021.10.021

PMID:34788694

Abstract

OBJECTIVES

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 (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR).

RESULTS

Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens 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.

CONCLUSION

Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.

摘要

目的

lefamulin 是一种截短侧耳素类抗生素，已获批准用于治疗社区获得性细菌性肺炎（CABP），本研究旨在评估其在 LEAP 1 和 2 两项 3 期临床试验的预设汇总分析中的微生物学疗效，这些研究均入组了 CABP 患者。

方法

在 LEAP 1 研究中，PORT 风险分类 III-V 级的成年患者接受静脉注射（IV） lefamulin 150 mg，每 12 小时 1 次（q12h），疗程 5-7 天，或莫西沙星 400 mg，每日 1 次（q24h），疗程 7 天，可选择 IV 至口服的转换。在 LEAP 2 研究中，PORT II-IV 级的成年患者接受口服 lefamulin 600 mg，每 12 小时 1 次，疗程 5 天，或莫西沙星 400 mg，每日 1 次，疗程 7 天。主要终点为治疗开始后 96±24 小时的早期临床应答（ECR）和末次给药后 5-10 天的研究者评估的临床应答（IACR）。次要终点包括基线 CABP 病原体患者的 ECR 和 IACR（通过培养、尿抗原检测、血清学和/或实时 PCR 检测到）。

结果

在 1289 例患者中（微生物学意向治疗人群），709 例（55.0%）患者的基线 CABP 病原体可被检出。最常见的病原体为肺炎链球菌（61.9%的患者）和流感嗜血杆菌（29.9%）；25.1%的患者存在非典型病原体，33.1%的患者存在混合感染。最常通过痰液 PCR 检测到病原体，其次是呼吸道标本培养。在基线 CABP 病原体患者中，lefamulin 的 ECR 率为 89.3%，莫西沙星为 93.0%；IACR 成功率分别为 83.2%和 86.7%。结果在 CABP 病原体中一致，包括耐药分离株和混合感染。