无菌制剂车间环境微生物污染情况监测

目的：采集无菌制剂生产车间洁净区环境微生物，应用全自动微生物检测系统进行监测分析，并进行耐药分析。方法：采样方法有沉降菌法、定量空气浮游菌采样法和表面取样法，对采集到的沉降菌、浮游菌、人员及设备表面微生物按照菌种鉴定仪使用说明书操作进行菌种鉴定和耐药性检测。结果：从345个样本中，检出微生物115株，其中沉降菌105株，浮游菌6株，人员及表面微生物4株；115株菌鉴定为46个菌种，分属于20个菌属。可信限均在95%以上。其中还检出了3株耐药菌。结论：对无菌GMP车间环境微生物进行监测，并建立药品GMP生产企业微生物信息库，可以更好地指导药品GMP企业实现有效的微生物管理。

Objective: To supervise microorganisms collected in environment of sterile products workshop with automatic microbial detection system and analyse their antibiotic resistance. Methods: Method of settlement of bacteria,quantitative airborne phytoplankton and sampling surface sampling were used. Collected bacteria identification and drug resistance detection were carried out according to the instructions of strain tester. Results: 115 microbial strains were checked out from 345 samples,including 105 strains of settled bacteria,6 strains of planktonic bacteria and 4 strains of bacteria on personnel and equipment. The 115 strains were identified as 46 species,belonging to 20 genera. The confidence limit is above 95%. Three antibiotic resistant strains were also detected. Conclusion: Monitoring the environmental microorganisms in aseptic GMP workshops,and establishing the microbial information database of pharmaceutical GMP manufacturers can better guide GMP enterprises to realize effective microbial management.

[1] 池王胄,宋庭,周芳芳,等.微生物鉴定技术在无菌药品生产企业中的应用[J].中国医药导刊,2012,14(1):169 CHI WZ,SONG T,ZHOU FF,et al.Application of microbe technology in the industry of sterile medicine[J].Chin J Med Guide,2012,14(1):169
[2] 魏桂梅,张金甲.浅析"欣弗事件"-药品质量管理认识[J].中医临床研究,2015,7(25):123 WEI GM,ZHANG JJ.An analysis of the Xinfu event-knowledge about medicine quality management[J].Clin J Chin Med,2015, 7(25):123
[3] 陈晓莉.从"齐二药"、"欣弗"等药害事件分析药品生产和监管环节存在的问题[J].中国药事,2008,22(10):871 CHEN XL.Analysis of the existing problems in the drug manufacturing and drug supervision and management from the "Qi Er Yao" counterfeit event and "Xin Fu"drug accidents[J].Chin Pharm Aff,2008,22(10):871
[4] 药品生产质量管理规范.2010年修订[S].2011 GMP.2010 Revision[S].2011
[5] 张爱萍,孙咸泽.药品GMP指南[M].北京:中国医药科技出版社,2011 ZHANG AP,SUN XZ.Drug GMP Guide[M].Beijing:China Medical Science Press,2011
[6] GB/T16293-2010医药工业洁净室(区)浮游菌的测试方法[S].2010 GB/T16293-2010 Test Method for Airbore Microbe in Clean Room(Zone)of the Pharmaceutiacal Industry[S].2010
[7] GB/T16294-2010医药工业洁净室(区)沉降菌的测试方法[S].2010 GB/T16294-2010 Test Method for Settling Microbe in Clean Room(Zone)of the Pharmaceutiacal Industry[S].2010
[8] 方杰,陈春丽,晏廷亮.健康人体内常见正常菌群的耐药性分析[J].教育现代化,2015,13(12):239 FANG J,CHEN CL,YAN TL.Analysis of drug resistance of normal bacteria in healthy people[J].Educ Mod,2015,13(12):239
[9] HASSAN RM,BASSIOUNY DM,MATAR Y.Bacteremia caused by Kocuria kristinae from Egypt:are there more? a case report and review of the literature[J].Case Rep Infect Dis,2016(1):1
[10] KIMURA MM,KAWAI E,YAOITA H,et al.Centralve-nouscatheter-related blood stream infection with Kocuria kristinae in a patient with propionic acidemia[J].Case Rep Infect Dis,2017(1):125
[11] 杨锐,郭玉荣,魏晓红,等.86株库克菌的鉴定与抗菌药物敏感性试验[J].国际检验医学杂志,2016,37(9):1214 YANG R,GUO YR,WEI XH,et al.86 strains of Kocuria bacteria identificatiaon and antimicrobial susceptibility test[J].Int J Lab Med,2016,37(9):1214
[12] 范一灵,冯震,钟玮,等.无菌药品生产企业核心区微生物污染调查与分析[J].中国药事,2014,28(6):586 FAN YL,FENG Z,ZHONG W,et al.Investigation and analysis of microbiological contamination core area of sterile drug manufacturing enterprises[J].Chin Pharm Aff,2014,28(6):586
[13] 户美玲,陈佩,严东珍,等.建立洁净区微生物数据库与无菌药品GMP生产过程控制的探讨[J].微生物学免疫学进展,2013,41(3):33 HU ML,CHEN P,YAN DZ,et al.Study on establishing a microorganism database of clean areas and GMP manufacturing process-control for sterile medicinal products[J].Prog Microbiol Immunol,2013,41(3):33
[14] 王秀梅.浅析新版无菌药品生产环境监测[J].山东化工,2013,42(9):187 WANG XM.Analysis of environment monitoring of sterile drug production in new GMP[J].Shandong Chem Ind,2013,42(9):187
[15] 杨燕,孙梦家,蒋波,等.药品无菌检查中污染微生物的鉴定与OOS调查分析[J].中国医药工业杂志,2016,47(12):1559 YANG Y,SUN MJ,JIANG B,et al.Identification and out-of-specification survey for contaminated isolates from sterility test[J].Chin J Pharm,2016,47(12):1559
[16] 朱晓燕,陈伟盛,关倩明.药品无菌检查OOS结果的调查和分析[J].中国药事,2017,31(7):751 ZHU XY,CHEN WS,GUAN QM.On the OOS results of drug sterile examination[J].Chin Pharm Aff,2017,31(7):751
[17] 李杨,李苏利.凝固酶阴性葡萄球菌的感染现状及耐药对策[J].医学综述,2005,11(9):848 LI Y,LI SL.The infection status of coagulase-negative staphylococcus and its drug resistance[J].Med Recapit,2005,11(9):848
[18] 贾华云,王岚,胡旃,等.湖南省即食食品中食源性致病菌污染状况及耐药性研究[J].实用预防医学,2013,20(1):16 JIA HY,WANG L,HU Z,et al.Contamination status of food borne pathogenic bacteria in instant food in hunan and their antibiotic resistance[J].Pract Prev Med,2013,20(1):16
[19] 费樱,刘晓丹,刘宝,等.2008年-2016年临床分离革兰阳性球菌的分布及耐药性分析[J].中国卫生检验杂志,2018,28(10):1193 FEI Y,LIU XD,LIU B,et al.Clinical distribution and drug resistance of Gram-positive cocci during 2008-2016[J].Chin J Health Lab Technol,2018,28(10):1193
[20] 吕国平,李亚子,李丽婕,等.空气环境中葡萄球菌的鉴定及耐药性分析[J].环境与健康杂志,2018,35(2):175 Lü GP,LI YZ,LI LJ,et al.Identification and drug resistance analysis of Staphylococci in air[J].J Environ Health,2018,35(2):175
[21] 何汉江,谭立志.葡萄球菌对氟喹诺酮类药物耐药机制研究进展[J].湘南学院学报,2004,6(3):60 HE HJ,TAN LZ.Progress in staphylococcus resistance to fluoroquinolones[J].J Xiangnan Univ,2004,6(3):60
[22] 梁业飞.喹诺酮类抗菌药物的临床应用研究进展[J].中国现代医生,2015,53(33):153 LIANG YF.Research progress of clinical application of quinolones[J].China Mod Doctor,2015,53(33):153