克柔念珠菌的耐药机制及抗真菌对策研究进展
|
摘要
由于临床上抗真菌药物的广泛使用,致使真菌耐药现象日趋严重。诸多研究数据表明,对氟康唑天然耐药的克柔念珠菌耐药率最高,已经成为临床上最为难治的念珠菌。本文针对克柔念珠菌感染及耐药现状、耐药机制以及抗克柔念珠菌对策的研究进展这几大方面做一综述。
Due to the widespread use of antifungal drugs in clinical practice, fungus resistance is becoming more and more serious. Many research data show that the resistant rate to fluconazole is the highest and it has become the most difficult candida to be treated in clinical practice. This paper reviews the current situation of infection and drug resistance of candida clorbicans, the mechanism of drug resistance and the research progress of anti-candida clorbicans.
Due to the widespread use of antifungal drugs in clinical practice, fungus resistance is becoming more and more serious. Many research data show that the resistant rate to fluconazole is the highest and it has become the most difficult candida to be treated in clinical practice. This paper reviews the current situation of infection and drug resistance of candida clorbicans, the mechanism of drug resistance and the research progress of anti-candida clorbicans.
引文
[1]董亚平,张媛媛,刘峰.深部念珠菌的临床分布及耐药分析[J].现代实用医学,2017,29(4):532-533.
[2]程卫萍.179例外阴阴道念珠菌的菌种分布及耐药分析[J].中国真菌学杂志,2016,11(1):44-45.
[3]熊志刚.深部酵母菌感染分布及耐药性分析[J].检验医学与临床,2017,14(9):1218-1220.
[4]赵丽莉.假丝酵母菌属感染的抗真菌药物分析[J].临床研究,2017,15(8):182-183.
[5]王玮玮,王厚照.妊娠期女性念珠菌感染调查及耐药性分析[J].国际检验医学杂志,2015,36(3):343-344.
[6]魏丹.医院念珠菌感染的临床分布及耐药性[J].中国实用医药,2016,11(1):166-167.
[7]李岸英,杨卫,李继慧,等.404例阴道念珠菌感染菌群分布和耐药性分析[J].中国妇幼保健,2009,24(31):4363-4364.
[8]王忠慧.医院361例真菌感染情况调查[J].疾病监测与控制杂志,2017,11(4):296.
[9]李文波,刘丽华,张玉娟,等.2010-2012年医院感染真菌的临床分布及耐药性分析[J].国际检验医学杂志,2013,34(18):2409-2412.
[10]ZhouZL,LinCC,ChuWL,etal.Thedistribution anddrugsusceptibilitiesofclinicalCandida speciesinTSARY2014[J].DiagnMicrobiolInfect Dis,2016,86(4):399-404.
[11]Vallabhaneni S, Cleveland A A, Farley MM, et al.Epidemiologyandriskfactorsforechinocandin nonsusceptibleCandidaglabratabloodstream infections:data from a large multisite population-based Candidemia surveillance program,2008-2014[J].Open Forum Infect Dis,2015,2(1):163-169.
[12]XuY,ChenL,LiC,etal.Susceptibilityofclinical isolates of Candia species to fluconazole and detection of Candida albicans ERG11 mutations[J].J Antimicrob Chemother,2008,61(4):798-804.
[13]Znaidi S, Weber S,Al-Abdin OZ,et al.Genomewide locationanalysisofCandidaalbicansUpc2p,a regulatorofsterolmetabolismandazoledrug resistance[J].Eukaryot Cell,2008,7(5):836-847.
[14]Heimann CJ,Schneider S,Barker KS,et al.An A643T mutationinthetranscriptionfactorUpc2pcauses constitutiveERG11upregulationandincreased fluconazoleresestanceinCandidaalbicans[J].Antimicrob Agents Chemother,2010,54(1):353-359.
[15]SelmeckiA,Gerami-NejadM,PaulsonC,etal.An isochromosomeconfersdrugresistanceinvivoby amplification of two genes,ERG11 and TAC1[J].Mol Microbiol,2008,68(3):624-641.
[16]KatiyarSK,EdlindTD.2001.Identificationand expressionofmultidrugresistance-relatedABC transportergenesinCandidakrusei[J].MedMycol,39:109-116.
[17]FranzR,KellySL,LambDC,etal.Muitiple molecularmechanismscontributetoastepwise developmentoffluconazoleresistanceinclinical Candidaalbicansstrains[J].AntimicrobAgents Chemother,1998,42:3065-3072.
[18]OrozcoA S, HigginbothamL M, Hitchcock CA,etal.Mechanismoffluconazoleresistancein Candidakrusei[J].AntimicrobAgentsChemoth er,1998,42(10):2645-2649.
[19]Mukherjee P K,Chandra J,Kuhn DM,etal.Mechanism of fluconazole resistance in Candida albicans biofilms:phase-specificrole ofeffluxpumpsandmembranesterols[J].Infect Immum,2003,71:4333-4340.
[20]龙冬艳,胡少平,陈新才,等.持留菌及其对微生物膜的耐受性影响研究进展[J].应用生态学报,2010,21(10):2707-2714.
[21]KEREN I,KALDALU N,SPOERING A,et al.Persister cells and tolerance to antimicrobials[J].FEMS Microbiol Letters,2004,230(1):13-18.
[22]张维杰,李辉,刘广彬.克柔念珠菌耐药机制的研究[J].中国医药指南,2012,10(33):380-381.
[23]王彦,黄海,李健峰,等.真菌耐药的研究进展[J].药学服务与研究,2009,9(3):166-169.
[24]Mishra N N,Prasad T, Sharma N, et al.Pathogenicity and drug resistance in Candida aalbicans and other yeast species. A review[J].Act a Micrbiol Immunol Hung,2007,54(3):201-235.
[25]Steier Z,Vermitsky JP,Toner G,et al.Flucytosine antagonism of azole activity versus candida glabrata:role of transcription factor Pdrl and multidrug transporter Cdrl[J].Antimicrob Agents Chemother,2013,57(11):5543-5547.
[26]PfallerMA,DiekamaDJ.Epidemiologyofinvasive candidasis:a persistent public health problem[J].Clin Microbiol Rev,2007,20(1):133-163.
[27]KahnJN,Garcia-EffronG,HsuMJ,etal.Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase[J].Antimicrob Agents Chemother,2007,51(5):1876-1878.
[28]廖万清,顾菊林.真菌耐药的现状与对策[J].药学服务与研究,2006,6(3):161-164.
[29]李瑞芳,卢研博,陈士华,等.动物内源性多肽CGA-N46生物信息学分析[J].动物医学进展,2013,34(4):43-46.
[30]李瑞芳,张添元,罗进贤,等.嗜铬粒蛋白N区抗真菌活性片段研究[J].中山大学学报,2006,45(2):4055-4059.
[31]张琳,李瑞芳,张慧茹,等.抗菌肽CGA-N46对皮肤感染克柔念珠菌小鼠的治疗作用[J].动物医学进展,2015,36(6):111-115.
[32]Garcia-Hermoso D,Desnos-Ollivier M.Typing candida speciesusingmicrosatellitelengthpolymorphism andmultiocussequencetyping[J].MethodsMol Biol,2016,1356(1):199-214.
[33]Tan YL, Leonhard M, Moser DA.Antibiofilm activity ofcarboxymethychitosanonthebiofilmsofnonCandidaalbicansCandidaspecies[J].Carbohydr Polym,2016,149(1):77-82.
[34]Livermore J,Hope W.Evaluation of the pharmacokinetics andclinicalutilityofisavuconzolefortreatmentof invasive fungal infections[J].Expert Opin Drug Metab Toxicol,2012,8(6):759-765.
[35]Sigurgeirsson B, van Rossem K, Malahias S,et al. 2013.A phaseⅡ,randomized, doubleblind, placebocontrolled,parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onycho-mycosis[J].J Am Acad Dermatol, 69:416-425.
[36]夏家栋.福司氟康唑合成方法研究进展[J].广东化工,2015,42(309):95-96,110.
[37]Huang S, Cao Y Y, Dai B D, et al.In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistance to fluconazole[J]. Biol Pharm Bull,2008,31(12):2234-2236.
[38]王维欣,齐丽丽,赵静,等.没食子酸联合氟康唑抗耐药非白念珠菌作用的体外试验[J].中国医院药学杂志,2017,37(23):2330-2334.
[39]DELATTIN N,DE BRUCKER K,VANDAMME K,et al.Repurposing as a means to increase the activity of amphotericin B and caspofungin against Candida albicans biofilms[J].J Antimicrob Chemother,2014,69(4):1035-1044.
[40]谢海伟,杨贤松,吕超田,等.抗真菌药物及作用机制研究[J].中国微生态学杂志,2015,27(12):1477-1479.
[41]林丽华,余加林,林雅茵,等.大蒜素对铜绿假单胞菌生物膜早期粘附及胞外多糖的影响[J].中国微生态学杂志,2009,21(1):9-12.
[2]程卫萍.179例外阴阴道念珠菌的菌种分布及耐药分析[J].中国真菌学杂志,2016,11(1):44-45.
[3]熊志刚.深部酵母菌感染分布及耐药性分析[J].检验医学与临床,2017,14(9):1218-1220.
[4]赵丽莉.假丝酵母菌属感染的抗真菌药物分析[J].临床研究,2017,15(8):182-183.
[5]王玮玮,王厚照.妊娠期女性念珠菌感染调查及耐药性分析[J].国际检验医学杂志,2015,36(3):343-344.
[6]魏丹.医院念珠菌感染的临床分布及耐药性[J].中国实用医药,2016,11(1):166-167.
[7]李岸英,杨卫,李继慧,等.404例阴道念珠菌感染菌群分布和耐药性分析[J].中国妇幼保健,2009,24(31):4363-4364.
[8]王忠慧.医院361例真菌感染情况调查[J].疾病监测与控制杂志,2017,11(4):296.
[9]李文波,刘丽华,张玉娟,等.2010-2012年医院感染真菌的临床分布及耐药性分析[J].国际检验医学杂志,2013,34(18):2409-2412.
[10]ZhouZL,LinCC,ChuWL,etal.Thedistribution anddrugsusceptibilitiesofclinicalCandida speciesinTSARY2014[J].DiagnMicrobiolInfect Dis,2016,86(4):399-404.
[11]Vallabhaneni S, Cleveland A A, Farley MM, et al.Epidemiologyandriskfactorsforechinocandin nonsusceptibleCandidaglabratabloodstream infections:data from a large multisite population-based Candidemia surveillance program,2008-2014[J].Open Forum Infect Dis,2015,2(1):163-169.
[12]XuY,ChenL,LiC,etal.Susceptibilityofclinical isolates of Candia species to fluconazole and detection of Candida albicans ERG11 mutations[J].J Antimicrob Chemother,2008,61(4):798-804.
[13]Znaidi S, Weber S,Al-Abdin OZ,et al.Genomewide locationanalysisofCandidaalbicansUpc2p,a regulatorofsterolmetabolismandazoledrug resistance[J].Eukaryot Cell,2008,7(5):836-847.
[14]Heimann CJ,Schneider S,Barker KS,et al.An A643T mutationinthetranscriptionfactorUpc2pcauses constitutiveERG11upregulationandincreased fluconazoleresestanceinCandidaalbicans[J].Antimicrob Agents Chemother,2010,54(1):353-359.
[15]SelmeckiA,Gerami-NejadM,PaulsonC,etal.An isochromosomeconfersdrugresistanceinvivoby amplification of two genes,ERG11 and TAC1[J].Mol Microbiol,2008,68(3):624-641.
[16]KatiyarSK,EdlindTD.2001.Identificationand expressionofmultidrugresistance-relatedABC transportergenesinCandidakrusei[J].MedMycol,39:109-116.
[17]FranzR,KellySL,LambDC,etal.Muitiple molecularmechanismscontributetoastepwise developmentoffluconazoleresistanceinclinical Candidaalbicansstrains[J].AntimicrobAgents Chemother,1998,42:3065-3072.
[18]OrozcoA S, HigginbothamL M, Hitchcock CA,etal.Mechanismoffluconazoleresistancein Candidakrusei[J].AntimicrobAgentsChemoth er,1998,42(10):2645-2649.
[19]Mukherjee P K,Chandra J,Kuhn DM,etal.Mechanism of fluconazole resistance in Candida albicans biofilms:phase-specificrole ofeffluxpumpsandmembranesterols[J].Infect Immum,2003,71:4333-4340.
[20]龙冬艳,胡少平,陈新才,等.持留菌及其对微生物膜的耐受性影响研究进展[J].应用生态学报,2010,21(10):2707-2714.
[21]KEREN I,KALDALU N,SPOERING A,et al.Persister cells and tolerance to antimicrobials[J].FEMS Microbiol Letters,2004,230(1):13-18.
[22]张维杰,李辉,刘广彬.克柔念珠菌耐药机制的研究[J].中国医药指南,2012,10(33):380-381.
[23]王彦,黄海,李健峰,等.真菌耐药的研究进展[J].药学服务与研究,2009,9(3):166-169.
[24]Mishra N N,Prasad T, Sharma N, et al.Pathogenicity and drug resistance in Candida aalbicans and other yeast species. A review[J].Act a Micrbiol Immunol Hung,2007,54(3):201-235.
[25]Steier Z,Vermitsky JP,Toner G,et al.Flucytosine antagonism of azole activity versus candida glabrata:role of transcription factor Pdrl and multidrug transporter Cdrl[J].Antimicrob Agents Chemother,2013,57(11):5543-5547.
[26]PfallerMA,DiekamaDJ.Epidemiologyofinvasive candidasis:a persistent public health problem[J].Clin Microbiol Rev,2007,20(1):133-163.
[27]KahnJN,Garcia-EffronG,HsuMJ,etal.Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase[J].Antimicrob Agents Chemother,2007,51(5):1876-1878.
[28]廖万清,顾菊林.真菌耐药的现状与对策[J].药学服务与研究,2006,6(3):161-164.
[29]李瑞芳,卢研博,陈士华,等.动物内源性多肽CGA-N46生物信息学分析[J].动物医学进展,2013,34(4):43-46.
[30]李瑞芳,张添元,罗进贤,等.嗜铬粒蛋白N区抗真菌活性片段研究[J].中山大学学报,2006,45(2):4055-4059.
[31]张琳,李瑞芳,张慧茹,等.抗菌肽CGA-N46对皮肤感染克柔念珠菌小鼠的治疗作用[J].动物医学进展,2015,36(6):111-115.
[32]Garcia-Hermoso D,Desnos-Ollivier M.Typing candida speciesusingmicrosatellitelengthpolymorphism andmultiocussequencetyping[J].MethodsMol Biol,2016,1356(1):199-214.
[33]Tan YL, Leonhard M, Moser DA.Antibiofilm activity ofcarboxymethychitosanonthebiofilmsofnonCandidaalbicansCandidaspecies[J].Carbohydr Polym,2016,149(1):77-82.
[34]Livermore J,Hope W.Evaluation of the pharmacokinetics andclinicalutilityofisavuconzolefortreatmentof invasive fungal infections[J].Expert Opin Drug Metab Toxicol,2012,8(6):759-765.
[35]Sigurgeirsson B, van Rossem K, Malahias S,et al. 2013.A phaseⅡ,randomized, doubleblind, placebocontrolled,parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onycho-mycosis[J].J Am Acad Dermatol, 69:416-425.
[36]夏家栋.福司氟康唑合成方法研究进展[J].广东化工,2015,42(309):95-96,110.
[37]Huang S, Cao Y Y, Dai B D, et al.In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistance to fluconazole[J]. Biol Pharm Bull,2008,31(12):2234-2236.
[38]王维欣,齐丽丽,赵静,等.没食子酸联合氟康唑抗耐药非白念珠菌作用的体外试验[J].中国医院药学杂志,2017,37(23):2330-2334.
[39]DELATTIN N,DE BRUCKER K,VANDAMME K,et al.Repurposing as a means to increase the activity of amphotericin B and caspofungin against Candida albicans biofilms[J].J Antimicrob Chemother,2014,69(4):1035-1044.
[40]谢海伟,杨贤松,吕超田,等.抗真菌药物及作用机制研究[J].中国微生态学杂志,2015,27(12):1477-1479.
[41]林丽华,余加林,林雅茵,等.大蒜素对铜绿假单胞菌生物膜早期粘附及胞外多糖的影响[J].中国微生态学杂志,2009,21(1):9-12.