黏质沙雷菌耐药性及碳青霉烯类抗生素耐药机制研究
Antibiotics resistance and the carbapenems-resistant mechanisms in Serratia marcescens
摘要目的 探讨黏质沙雷菌分离株的整体耐药特点,研究其对碳青霉烯类药物耐药的主要机制.方法 收集2007至2010年从宁波市第一医院不同病区分离(剔除重复菌株)黏质沙雷菌247株,用Vitek2 -Compact及配套革兰阴性杆菌药敏卡(GNS)检测其药敏情况,对筛选出的20株耐碳青霉烯类菌株进行PCR检测其耐药基因.结果 黏质沙雷菌对头孢曲松、氨曲南、环丙沙星的耐药率较高,分别为70.4%( 174/247)、64.8% (160/247)、57.4% (142/247);对阿米卡星、庆大霉素、亚胺培南、美罗培南的耐药率较低,分别为:3.5%( 8/229)、5.4%( 13/241)、5.9%(14/237)、8.1% (20/247).PCR检测20株对碳青霉烯类抗生素耐药的黏质沙雷菌中,1、7、12和16号的AmpC染色体基因表达是阴性参考菌株的98.3、102.3、121.5、87.3倍;共有12株黏质沙雷菌分离株同时携带CTX-M型超广谱β内酰胺酶(ESBLs)和KPC-2型碳青霉烯类酶.黏质沙雷菌所携带的CTX-M以CTX-M1、CTX-M2、CTX-M9为主;2株菌携带有SHV基因;2株菌携带有SME基因;2株菌携带有TEM基因;5株菌膜孔蛋白基因ompC和ompF均缺失;仅1株ompC基因缺失;2株菌ompF基因缺失.结论 黏质沙雷菌对β内酰胺类药物耐药的原因比较复杂,以产β内酰胺酶为主.开展对耐药菌株的进化和多耐药基因的研究,有利于合理应用抗菌药物,降低抗生索对耐药菌的选择压力及控制耐药菌株的蔓延.
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abstractsObjective To find out the antimicrobial resistance of clinical sequential isolates of Serratia marcescens,investigate the primary antimicrobial resistant mechanism of Serratia marcescens to β-lactams antibiotics.Methods Review the antimicrobial resistance data of 247 Serratia marcescens isolates collected sequentially from different clinical wards during 2007 to 2010 in the First Hospital of Ningbo,which their antimicrobial susceptihility testing was got by using Vitek2-Compact system and matching products of gram-negative susceptibility card (GNS).The antimicrobial resistant genes of 20 carbapenems resistant isolates were detected by PCR.Results The Serratia marcescens resistant rates to ceftriaxone,aztreonarn and ciprofloxacin in our hospital were 70.4% ( 174/247 ),64.8% ( 160/247 ),57.4% ( 142/247),respectively,the resistant rates were lower to amikacin,gentamicin,imipenem and meropenem,which were 3.5% ( 8/229 ),5.4% ( 13/241 ),5.9% ( 14/237 ),8.1% ( 20/247 ),respectively.PCR experiment showed that the expression levels of the AmpC gene in 4 strains were higher than that of the negative reference strains.The expression levels were 98.3,102.3,121.5,87.3 times compared to the negative reference strains,respectively.Twelve strains (strain no.2,3,5,6,9,10,14,15,16,17,18 and 19) produce both blaCTX-M and blaKPC-2 enzymes.Highly deteced hlaCTX-M of Serratia marcescens in our hospital included CTX-M1,CTX-M2,CTX-M9.Isolates no.7 and 18 were carrying blaSHV gene,Isolates no.8 and 13 were carrying blaSME,Isolates no.11 and 20 were carrying blaTEM.There were 5 strains (no.3,4,5,7 and 16) lose the outer membrane protein (OMP) genes ompC and ompF.Two strains( no.1 and 12 ) lose OMP gene ompF only,and one strain ( no.20 ) was lose OMP gene ompC only.Conclusions The cause of β-lactam antibiotics resistance of Serratia marcescens was complicated,and the most important mechanism is producing β-1actams and loss of OMP.Understanding the evolution and drug resistant mechanisms will help for best use of antibiotics and reducing the selection of antibiotics to resistant isolates.
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