Eraikhuemen Nathaniel, Julien Daniel, Kelly Alandra, Lindsay Taylor, Lazaridis Dovena
Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Davie, FL, USA.
Memorial Regional Hospital South, Hollywood, FL, USA.
Infect Dis Ther. 2021 Mar;10(1):149-163. doi: 10.1007/s40121-020-00378-3. Epub 2021 Feb 2.
The goal of this article is to review the clinical pharmacology, pharmacokinetics, efficacy, and safety of lemafulin.
We performed a systematic literature review using the search terms of lefamulin and BC-3781 in the PubMed and EMBASE databases. We also cross-referenced the pertinent articles and searched ClinicalTrials.gov to identify ongoing and nonpublished studies.
Published data from 2005 to 2019 evaluating the clinical pharmacology, efficacy, and safety studies of lefamulin were analyzed.
In phase 3 clinical trials, two multicenter, randomized double-blinded studies-Lefamulin Evaluation Against Pneumonia 1 and 2 (LEAP 1 and 2)-compared the efficacy and safety of lemafulin with moxifloxacin in patients diagnosed with community-acquired bacterial pneumonia (CABP). Lemafulin given in doses of 600 mg orally or 150 mg intravenously were reported to have comparable efficacy to those of moxifloxacin with or without linezolid in patients with CABP. After the trial, the lefamulin group had an early clinical response (ECR) of 87.3% and the moxifloxacin group had an ECR of 90.2%. The difference of - 2.9% in the ECR was non-significant (CI - 8.5, 2.8).
Lemafulin exhibits a unique binding property; therefore, it possess a potentially lower predisposition for the development of bacterial resistance and cross-resistance to other antimicrobial classes. Lefamulin is active against gram-positive including methicillin-resistant strains and atypical organisms which are often implicated in CABP. Lefamulin may be a safe alternative for adult patients with CABP who may not be candidates for respiratory fluoroquinolones. Lefamulin demonstrates both bactericidal and bacteriostatic activity against gram-positive, fastidious gram-negatives, atypical pathogens, and some gram-negative anaerobes. It is bactericidal in vitro against Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae (including macrolide-resistant strains) at concentrations of 0.06, 0.5, and 0.008 µg/ml respectively, and bacteriostatic against Staphylococcus aureus and Streptococcus pyogenes. The agent also demonstrates both time- and concentration-dependent killing against the pathogens S. pneumoniae and S. aureus. In vitro susceptibility testing demonstrated an MIC of 0.06/0.12 µg/ml against S. pneumoniae and S. aureus. The SENTRY Antimicrobial Surveillance Program found that at a concentration ≤ 1 µg/ml, lefamulin inhibited 100% S. pneumoniae isolates, 99.8% of S. aureus isolates, and 99.6% of methicillin-resistant S. aureus isolates. It was not affected by resistance to various antibiotic classes such as beta-lactams, fluoroquinolones, or macrolides.
本文旨在综述来法莫林的临床药理学、药代动力学、疗效及安全性。
我们在PubMed和EMBASE数据库中使用“来法莫林”和“BC-3781”作为检索词进行了系统的文献综述。我们还交叉引用了相关文章，并检索了ClinicalTrials.gov以识别正在进行和未发表的研究。
分析了2005年至2019年发表的评估来法莫林临床药理学、疗效及安全性研究的数据。
在3期临床试验中，两项多中心、随机双盲研究——来法莫林抗肺炎评估1和2（LEAP 1和2）——比较了来法莫林与莫西沙星在确诊为社区获得性细菌性肺炎（CABP）患者中的疗效和安全性。据报道，对于CABP患者，口服600mg或静脉注射150mg的来法莫林与使用或未使用利奈唑胺的莫西沙星疗效相当。试验结束后，来法莫林组的早期临床反应（ECR）为87.3%，莫西沙星组的ECR为90.2%。ECR中-2.9%的差异无统计学意义（CI -8.5, 2.8）。
来法莫林具有独特的结合特性；因此，它产生细菌耐药性和对其他抗菌类别的交叉耐药性的可能性较低。来法莫林对革兰氏阳性菌（包括耐甲氧西林菌株）和非典型病原体具有活性，这些病原体常与CABP有关。来法莫林可能是成年CABP患者的一种安全替代药物，这些患者可能不适合使用呼吸氟喹诺酮类药物。来法莫林对革兰氏阳性菌、苛养革兰氏阴性菌、非典型病原体和一些革兰氏阴性厌氧菌具有杀菌和抑菌活性。它在体外对肺炎链球菌、流感嗜血杆菌和肺炎支原体（包括耐大环内酯菌株）的杀菌浓度分别为0.06、0.5和0.008μg/ml，对金黄色葡萄球菌和化脓性链球菌具有抑菌作用。该药物对肺炎链球菌和金黄色葡萄球菌病原体还表现出时间和浓度依赖性杀菌作用。体外药敏试验显示对肺炎链球菌和金黄色葡萄球菌的MIC为0.06/0.12μg/ml。哨兵抗菌监测计划发现，在浓度≤1μg/ml时，来法莫林抑制100%的肺炎链球菌分离株、99.8%的金黄色葡萄球菌分离株和99.6%的耐甲氧西林金黄色葡萄球菌分离株。它不受对各种抗生素类别（如β-内酰胺类、氟喹诺酮类或大环内酯类）耐药性的影响。
