治疗医院获得性肺炎新药:murepavadin
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摘要
医院获得性肺炎是医院内常见的感染性疾病,主要由绿脓杆菌引起,有较高的发生率和死亡率。murepavadin是首个全新作用机制的环形类多肽药物,能选择性与绿脓杆菌外膜的脂多糖转运蛋白D相互作用,阻碍了脂多糖的转运,从而产生抗菌活性。murepavadin可有效治疗绿脓杆菌引起的包括呼吸机相关性肺炎在内的医院获得性感染,并有极好的安全性,展示了良好的临床应用前景。
Hospital-acquired pneumonia is one of the common nosocomial infections caused by Pseudomonas aeruginosa,which has the high morbidity and mortality.Murepavadin is the first peptidomimetic antibacterial drug with a novel mechanism.It selectively interacts with the lipopolysaccharide transport protein D(LptD) in outer membrane of Pseudomonas aeruginosa to hinder the transport of lipopolysaccharide and produce antimicrobial activity.Murepavadin is effective in the treatment of hospital-acquired infections including ventilator-associated pneumonia caused by Pseudomonas aeruginosa and has excellent safety,showing a good prospect for clinical application.
Hospital-acquired pneumonia is one of the common nosocomial infections caused by Pseudomonas aeruginosa,which has the high morbidity and mortality.Murepavadin is the first peptidomimetic antibacterial drug with a novel mechanism.It selectively interacts with the lipopolysaccharide transport protein D(LptD) in outer membrane of Pseudomonas aeruginosa to hinder the transport of lipopolysaccharide and produce antimicrobial activity.Murepavadin is effective in the treatment of hospital-acquired infections including ventilator-associated pneumonia caused by Pseudomonas aeruginosa and has excellent safety,showing a good prospect for clinical application.
引文
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[10]URFER M,BOGDANOVIC J,LO MONTE F,et al.Apeptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli[J].JBiol Chem,2016,291(4):1921-1932.
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[12]SRINIVAS N,JETTER P,UEBERBACHER BJ,et al.Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa[J].Science,2010,327(5968):1010-1013.
[13]THAKARE R,DASGUPTA A,CHOPRA S.Murepavadin[J].Drugs Fut,2018,43(3):161-173.
[14]LOU K.A new spin on protegrin[J].SciBX,2010,3(9):265.
[15]SADER HS,DALE GE,RHOMBERG PR,et al.Antimicrobial activity of murepavadin tested against clinical isolates of Pseudomonas aeruginosa from the United States,Europe,and China[J].Antimicrob Agents Chemother,2018,3(7):311-318.
[16]WACH A,DEMBOWSKY K,DALE GE,et al.Pharmacokinetics and safety of intravenous murepavadin infusion in healthy adult subjects administered single and multiple ascending doses[J].Antimicrob Agents Chemother,2018,62(4):e02355.
[2]KLEVENS RM,EDWARDS JR,RICHARDS CL,et al.Estimating health care-associated infections and deaths in U.S.hospitals,2002[J].Public Health Rep,2007,122(2):160-166.
[3]SPELLBERG B,TALBOT G.Recommended design features of future clinical trials of antibacterial agents for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia[J].Clin Infect Dis,2010,51(Suppl 1):S150-S170.
[4]TUMBARELLO M,DE PG,TRECARICHI EM,et al.Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients[J].Intensive Care Med,2013,39(4):682-692.
[5]JONES RN.Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia[J].Clin Infect Dis,2010,51(Suppl 1):S81-S87.
[6]MICEK ST,WUNDERINK RG,KOLLEF MH,et al.An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia:impact of multidrug resistance[J].Crit Care,2015,19:219.
[7]BOTOS I,MAJDALANI N,MAYCLIN SJ,et al.Structural and functional characterization of the LPS transporter LptDE from gram-negative pathogens[J].Structure,2016,24(6):965-976.
[8]WERNEBURG M,ZERBE K,JUHAS M,et al.Inhibition of lipopolysaccharide transport to the outer membrane in Pseudomonas aeruginosa by peptidomimetic antibiotics[J].Chembiochem,2012,13(12):1767-1775.
[9]LUTHER A,MOEHLE K,CHEVALIER E,et al.Protein epitope mimetic macrocycles as biopharmaceuticals[J].Curr Opin Chem Biol,2017,38:45-51.
[10]URFER M,BOGDANOVIC J,LO MONTE F,et al.Apeptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli[J].JBiol Chem,2016,291(4):1921-1932.
[11]BROWN DG,LISTER T,MAY-DRACKA TL.New natural products as new leads for antibacterial drug discovery[J].Bioorg Med Chem Lett,2014,24(2):413-418.
[12]SRINIVAS N,JETTER P,UEBERBACHER BJ,et al.Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa[J].Science,2010,327(5968):1010-1013.
[13]THAKARE R,DASGUPTA A,CHOPRA S.Murepavadin[J].Drugs Fut,2018,43(3):161-173.
[14]LOU K.A new spin on protegrin[J].SciBX,2010,3(9):265.
[15]SADER HS,DALE GE,RHOMBERG PR,et al.Antimicrobial activity of murepavadin tested against clinical isolates of Pseudomonas aeruginosa from the United States,Europe,and China[J].Antimicrob Agents Chemother,2018,3(7):311-318.
[16]WACH A,DEMBOWSKY K,DALE GE,et al.Pharmacokinetics and safety of intravenous murepavadin infusion in healthy adult subjects administered single and multiple ascending doses[J].Antimicrob Agents Chemother,2018,62(4):e02355.