治疗社区获得性肺炎的截短侧耳素类抗生素Lefamulin

摘要/Abstract

摘要： Lefamulin是首个可以全身用药的半合成截短侧耳素类抗生素，通过特殊的作用机制抑制细菌蛋白质的合成，有广谱的抗耐药性菌的活性。临床Ⅲ期试验证实了它的有效性和安全性，显示了良好的临床应用前景。Lefamulin于2019年8月获美国FDA批准，用于治疗社区获得性细菌性肺炎的成年患者。本文综述了Lefamulin的研究进展，包括药效学、药动学、临床疗效和安全性等，旨在为临床医生和患者提供有益的参考。

关键词: font-size:medium, ">Lefamulin；社区获得性肺炎；细菌耐药性

Abstract: Lefamulin is the first semi-synthetic pleuromutilin antibiotic for systemic administration， which exhibits the unique mechanism of action through inhibition of bacterial protein synthesis. The novel antibiotic was developed to combat the increasing incidence of bacterial resistance. Completed clinical phase III studies demonstrated the high efficacy and acceptable safety of Lefamulin monotherapy for community-acquired pneumonia in adults， showing the good prospect for the clinical application. Thus in August 2019 it was approved by U.S. FDA for the treatment of adult patients with community-acquired pneumonia. This article introduces the research advancement of Lefamulin about its pharmacodynamics， pharmacokinetics， clinical efficacy， and safety to provide reference for clinicians and patients.

Key words: font-size:medium, ">Lefamulin； Community-acquired pneumonia； Antimicrobial resistance

中图分类号:

罗志敏, 朱迎春, 王海荣. 治疗社区获得性肺炎的截短侧耳素类抗生素Lefamulin[J]. 中国医药导刊, 2020, 22(6): 397-400.

LUO Zhimin, ZHU Yingchun, WANG Hairong. Lefamulin as a New Pleuromutilin Antibiotic in the Treatment of Community-Acquired Pneumonia[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2020, 22(6): 397-400.

参考文献 30

[1]	Ramirez JA， Wiemken TL， Peyrani P， et al. Adults hospitalized with pneumonia in the United States：incidence， epidemiology， and mortality [J]. Clin Infect Dis， 2017， 65(11)：1806-1812.
[2]	Stupka JE， Mortensen EA， Anzueto A， et al. Community-acquired pneumonia in elderly patients [J]. Aging Health， 2009， 5(6)：763-774.
[3]	Jain S， Self WH， Wunderink RG， et al. Community-acquired pneumonia requiring hospitalization among U.S. adults [J]. N Engl J Med， 2015， 373(5)：415-427.
[4]	Cunha BA. Empiric therapy of community-acquired pneumonia：guidelines for the perplexed? [J]. Chest， 2004， 125(5)：1913-1919.
[5]	Armold FW， Summersgil JT， Lajoie AS， et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia [J]. Am J Respir Crit Care Med， 2007， 175(1)：1086-1093.
[6]	Mandell LA， Wunderink RG， Anzueto A， et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults [J]. Clin Infect Dis， 2007， 44(Supp 2)：S27-S72.
[7]	Lim WS， Baudouim SV， George RC， et al. BTS guidelines for the management of community acquired pneumonia in adults：update 2009 [J]. Thorax， 2009， 64 (Suppl 3)：iii1-55.
[8]	Ehsan M， Metersky ML， et al. Clinical management of community-acquired pneumonia [J]. Curr Respir Care Rep， 2013， 2：218-225.
[9]	Jones RN， Jacobs MR， Sader HS. Evolving trends in Streptococcus pneumoniae resistance：implications for therapy of community-acquired bacterial pneumonia[J]. Int J Antimicrob Agents， 2010， 36(3)：197-204.
[10]	Cherazard R， Epstein M， Doan TL， et al. Antimicrobial resistant Streptococcus pneumoniae：prevalence， mechanisms， and clinical implications [J]. Am J Ther， 2017， 24(3)：e361-e369.
[11]	Pereyre S， Goret J， Bébéar C. Mycoplasma pneumoniae：current knowledge on macrolide resistance and treatment [J]. Front Microbiol， 2016， 7：974.
[12]	陈代杰. 新世纪以来全球新型抗菌药物研发及前沿研究进展 [J]. 中国抗生素杂志， 2017， 42(3)：161-168.
[13]	Kavanag F， Hervey A， Robbins WJ. Antibiotic substances from basidiomycetes：VIII. Pleurotus multilus (Fr.) Sacc. and Pleurotus passeckerianus Pilat[J]. Proc Nat Acad Sci， 1951， 37(9)：570-574.
[14]	Islam KM， Klein U， Burch DG. The activity and compatibility of the antibiotic tiamulin with other drugs in poultry medicine-a review [J]. Poult Sci， 2009， 88(11)：2353-2359.
[15]	Dip R， Nemet Z， Schiessl B. Efficacy and tolerability of early administration of valnemulin hydrochloride premix on epizootic rabbit enteropathy [J]. Vet J， 2015， 204(3)：309-314.
[16]	Shawar R， Nicole SO， Dalessandro MB， et al. Topical retapamulin in the management of infected traumatic skin lesions [J]. Therap Clin Risk Manag， 2009， 5(1)：41-49.
[17]	Paukner S， Riedl R. Pleuromutilins：potent drugs for resistant bugs-mode of action and resistance [J]. Cold Spring Harb Perspect Med， 2017， 7(1)：a027110.
[18]	Novak R. Are pleuromutilin antibiotics finally fit for human use? [J]. Ann N Y Acad Sci， 2011， 1241：71-81.
[19]	Eyal Z， Matzov D， Krupkin M， et al. A novel pleuromutilin antibacterial compound， its binding mode and selectivity mechanism [J]. Sci Rep， 2016， 6：39004.
[20]	Sader HS， Paukner S， Ivezic-Schoenfeld Z， et al. Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs) [J]. J Antimicrob Chemother， 2012，67(5)：1170-1175.
[21]	Paukner S， Sader HS， Ivezic-Schoenfeld Z， et al. Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010 [J]. Antimicrob Agents Chemother， 2013， 57(9)：4489-4495.
[22]	Mendes RE， Farrell DJ， Flamm RK， et al. In vitro activity of lefamulin tested against Streptococcus pneumoniae with defined serotypes， including multidrug-resistant isolates causing lower respiratory tract infections in the United States [J]. Antimicrob Agents Chemother， 2016， 60(7)：4407-4411.
[23]	Waittes KB， Crabb DM， Duffy LB， et al. In vitro activities of lefamulin and other antimicrobial agents against macrolide-susceptible and macrolide-resistant mycoplasma pneumonia from the United States， Europe， and China [J]. Antimicrob Agents Chemother， 2017， 61(2)：e02008.
[24]	Jacobsson S， Paukner S， Golparin D， et al. In vitro activity of the novel pleuromutilin lefamulin (BC-3781) and effect of efflux pump inactivation on multidrug-resistant and extensively-drug resistant Neisseria gonorrhoeae[J]. Antimicrob Agents Chemother， 2017， 61(11)：e01497-e01417.
[25]	Zeitlinger M， Schwameis R， Burian A， et al. Simultaneous assessment of the pharmacokinetics of a pleuromutilin， lefamulin， in plasma， soft tissues and pulmonary epithelial lining fluid [J]. J Antimicrob Chemother， 2016， 71(4)：1022-1026.
[26]	Thakare R， Dasgupta A， Chopra S. Pleuromutilin antibacterial treatment of pneumonia and ABSSI [J]. Drugs of the Future， 2016， 41(3)：157-167.
[27]	File TM， Golderg L， Das A， et al. Efficacy and safety of intravenous-to-oral lefamulinin， a pleuromutilin antibiotic， for the treatment of community-acquired bacterial pneumonia：the phase 3 LEAP 1 trial [J]. Clin Infect Dis， 2019， 69(11)：1856-1867.
[28]	NCT02813694. Nabriva therapeutic (lefamulin) [EB/OL]. (2018-11-04) [2019-02-26]. https：//clinicaltrials.gov/ct2/show/NCT02813694.
[29]	Prince WT， Ivezic-Schoenfeld Z， Lell C， et al. Phase II clinical study of BC-3781， a pleuromutilin antibiotic， in treatment of patients with acute bacterial skin and skin structure infections[J]. Antimicrob Agents Chemother， 2013， 57(5)：2087-2094.
[30]	Sader HS， Biedenbach DJ， Paukner S， et al. Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against gram-positive organisms commonly associated with acute bacterial skin and skin structure infections [J]. Antimicrob Agents Chemother， 2012， 56(3)：1619-1623.

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