| 89 | 1 | 53 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 横断面调查江苏地区农田唑类耐药烟曲霉热点环境及流行特点。方法 江苏省苏北和苏南地区共采集68份农田土壤标本,通过培养分离烟曲霉菌株,进一步进行体外抗唑类药物敏感实验筛选唑类耐药烟曲霉(azole resistance Aspergillu fumigatus,RAF)菌株,并对分离的RAF菌株扩增cyp51A基因鉴定耐药突变表型。结果 68份农田土壤标本,共分离获得106株烟曲霉菌株,34株(34/106株,耐药率32%)为RAF,其中8株检测到cyp51A基因突变(7株TR46/Y121F/T289A,1株TR34/L98H/S297T/F495I),这8株RAF菌株对伊曲康唑、泊沙康唑和伏立康唑同时耐药,均对伏立康唑高度耐药(MIC>16 mg/L)。其余26株RAF菌株未检测到任何cyp51A基因突变;RAF在草莓田地最多(16株/34株),稻田次之(8株/34株);苏北农田RAF检出率高于苏南农田,深层土壤RAF检出率略高于表层土壤。结论 江苏农田RAF菌株检出率高达32%,以非cyp51A基因相关耐药机制为主。草莓大棚田地可能是江苏地区农田RAF产生的潜在热点,建议对农业中使用的杀菌剂进行管理,有助于控制临床上的真菌耐药问题。
Abstract:Objective We conducted a cross-sectional study to investigate hotspots environment and prevalence of azole-resistance Aspergillus fumigatus(RAF)isolates from agriculture fields in Jiangsu province. Methods Sixty-eight soil samples were taked in north and south area in Jiangsu province, Azole-resistant A. fumigatus were screened by selective medium and antifungal susceptibility test, cyp51A gene were amplified for detection of resistant mutation. Results Of 106 A. fumigatus isolates recovered from 68 soil samples, 34(32%) were azole resistant A. fumigatus. Eight of 34 had mutations in cyp51A gene(7 TR46/Y121F/T289A,1 TR34/L98H/S297T/F495I), the eight isolates were multi-resistant to itraconazole, voriconazole and posaconazole, and have MIC>16 mg/L to voriconazole. However, rest of 26 RAF isolates were not detected any mutation in cyp51A gene. Strawberry fields were detected the most frequently RAF isolates(16 in 34 isolates), followed by rice fields(8 in 34 isolates). RAF isolates in north Jiangsu were detected more frequently than those in south Jiangsu. RAF isolates from deeper soil were slightly more than those from superficial soil. Conclusion Our study results suggests that detection rate of RAF isolates in soil samples in Jiangsu agricultural fields was up to 32%, azole-resistance mechanism of A. fumigatus were mainly non-cyp51A gene related mechanism, Strawberry fields might be a potential hotspots for RAF. Managing the fungicides used in agriculture will help to control the emergence of antifungal drug resistance in clinics.
[1] TACCONE F S,VAN DEN ABEELE A M,BULPA P,et al.Epidemiology of invasive aspergillosis in critically ill patients:clinical presentation,underlying conditions,and outcomes[J].Crit Care,2015,19(1):7.
[2] VAN DE VEERDONK F L,KOLWIJCK E,LESTRADE P P,et al.Influenza-associated aspergillosis in critically Ill patients[J].Am J Respir Crit Care Med,2017,196(4):524-527.
[3] ALANIO A,DELLIèRE S,FODIL S,et al.Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19[J].Lancet Respir Med,2020,8(6):e48-e49.
[4] GANGNEUX J P,REIZINE F,GUEGAN H,et al.Is the COVID-19 pandemic a good time to include Aspergillus molecular detection to categorize aspergillosis in ICU patients?A monocentric experience[J].J Fungi (Basel),2020,6(3):105.
[5] VERWEIJ P E,CHOWDHARY A,MELCHERS W J G,et al.Azole resistance in Aspergillus fumigatus can we retain the clinical use of mold-active antifungal azoles[J].Clin Infect Dis,2016,62(3):362-368.
[6] PATTERSON T F,THOMPSON G R 3RD,DENNING D W,et al.Practice guidelines for the diagnosis and management of aspergillosis:2016 update by the Infectious Diseases Society of America[J].Clin Infect Dis,2016,63(4):e1-e60.
[7] LESTRADE P,MEIS J F,MELCHERS W,et al.Triazole resistance in Aspergillus fumigatus:recent insights and challenges for patient management[J].Clin Microbiol Infect,2019,25(7):799-806.
[8] VAN DER LINDEN J W,ARENDRUP M C,WARRIS A,et al.Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus[J].Emerg Infect Dis,2015,21(6):1041-1044.
[9] BUIL J B,HARE R K,ZWAAN B J,et al.The fading boundaries between patient and environmental routes of triazole resistance selection in Aspergillus fumigatus [J].PLoS Pathog,2019,15(8):e1007858.
[10] CHEN Y,DONG F,ZHAO J,et al.High azole resistance in Aspergillus fumigatus isolates from strawberry fields,China,2018[J].Emerg Infect Dis,2020,26(1):81-89.
[11] CAO D,WANG F,YU S,et al.Prevalence of azole-resistant Aspergillus fumigatus is highly associated with azole fungicide residues in the fields[J].Environ Sci Technol,2021,55(5):3041-3049.
[12] ZHOU D,KORFANTY G A,MO M,et al.Extensive genetic diversity and widespread azole resistance in greenhouse populations of Aspergillus fumigatus in Yunnan,China[J],mSphere,2021,6(1):e00066-21.
[13] WAYNE P.Reference method for broth dilution antifungal susceptibility testing of filamentous fungi,3rd ed.Approved standard.CLSI document M38-A3[S].Clinical and Laboratory Standards Institute,2017.
[14] WAYNE P.Epidemiological cutoff values for antifungal usceptibility testing,M59 3nd edition[S].Clinical and Laboratory Standards Institute,2020.
[15] BALLARD E,ZOLL J,MELCHERS W,et al..Raw genome sequence data for 13 isogenic Aspergillus fumigatus strains isolated over a 2 year period from a patient with chronic granulomatous disease[J].Data Brief,2019,25:104021.DOI:10.1016/j.dib.2019.104021.
[16] ?ZMERDIVEN G E,AK S,ENER B,et al.First determination of azole resistance in Aspergillus fumigatus strains carrying the TR34/L98H mutations in Turkey[J].J Infect Chemother,2015,21(8):581-586.
[17] REN J,JIN X,ZHANG Q,et al.Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields[J].J Hazard Mater,2017,326:54-60.DOI:10.1016/j.jhazmat.2016.12.013.
[18] WIEDERHOLD N P,GIL V G,GUTIERREZ F,et al.First detection of TR34 L98H and TR46 Y121F T289A cyp51 mutations in Aspergillus fumigatus isolates in the united states[J].J Clin Microbiol,2016,54(1):168-171.
[19] BADER O,WEIG M,REICHARD U,et al.Cyp51A-based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany[J].Antimicrob Agents Chemother,2013,57(8):3513-3517.
[20] Prigitano A,Venier V,Cogliati M,et al.Azole-resistant Aspergillus fumigatus in the environment of northern Italy,May 2011 to June 2012[J].Euro Surveill,2014,19(12):20747.
[21] TROVATO L,SCALIA G,DOMINA M,et al.Environmental isolates of multi-azole-resistant Aspergillus spp.in southern Italy[J].J Fungi (Basel),2018,4(4):131.
[22] CHOWDHARY A,SHARMA C,HAGEN F,et al.Exploring azole antifungal drug resistance in Aspergillus fumigatus with special reference to resistance mechanisms[J].Future Microbiol,2014,9(5):697-711.
基本信息:
中图分类号:R519
引用信息:
[1]刘晨,黄瑞,胡丹阳,等.唑类耐药烟曲霉在江苏不同农田流行特点研究[J].中国真菌学杂志,2023,18(06):511-517.
基金信息:
国家自然科学基金面上项目(NM 82272358); 苏州市科技计划项目(SKY2022037); 苏州高新区人民医院院管课题(SGY2019D02,SGY2021H01,SGY2021C01)
2023-12-29
2023-12-29