2012-2015年莫斯科地区碳青霉烯类非敏感医院内铜绿假单胞菌金属β-内酰胺酶的流行及外排介导机制

A. Lazareva, Лазарева Анна Валерьевна, O. Kryzhanovskaya, Крыжановская Ольга Андреевна, Y. Bocharova, Бочарова Юлия Александровна, I. Chebotar, Чеботарь Игорь Викторович, N. Mayanskiy, Маянский Николай Андреевич
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引用次数: 2

摘要

背景铜绿假单胞菌是主要的院内条件致病菌,是免疫功能低下患者感染性发病和死亡的重要原因。目的探讨金属β-内酰胺酶(MBL)在铜绿假单胞菌(P. aeruginosa)院内分离株对碳青霉烯耐药中的作用及外排介导的机制。方法对2012-2015年从莫斯科3家医院的儿童和成人患者中分离的碳青霉烯类不敏感铜绿假单胞菌进行分析。采用E-test评价碳青霉烯类药物的敏感性。此外,采用肉汤微量稀释法测定美罗培南的最低抑菌浓度(mic)。使用ED ta介导的抑制试验来确定MBL的存在。采用离子载体羰基氰化物3-氯苯基肼(CCCP)修饰的MIC法测定外排依赖性耐药性。结果共检出54株碳青霉烯类不敏感铜绿假单胞菌。在37株(69%)分离株中检测到MBL的存在,29株(54%)分离株具有外排介导的耐药性。在10株(19%)分离株中,既没有发现MBL,也没有发现外排活性。6株高活性外排株中有5株(83%)为mbl阳性。在外排活性低的分离株中,74%(17/23)具有MBL,而在无外排的分离株中,MBL阳性率为60%(15/25)。结论医院内铜绿假单胞菌中MBL和外排介导的碳青霉烯类耐药发生率较高。此外,我们的研究结果表明,几种抗性机制可能在分离水平结合在一起。这些数据可能有助于开发抗碳青霉烯耐药的新策略。
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[The Prevalence of Metallo-β-Lactamases and Efflux-Mediated Mechanisms in Carbapenem Nonsusceptible Nosocomial Pseudomonas aeruginosa Isolated in Moscow in 2012-2015].
BACKGROUND Pseudomonas aeruginosa, the major nosocomial opportunistic pathogen, is an important cause of infectious morbidity and mortality among immunocompromised patients. OBJECTIVE To establish the role of metallo-β-lactamases (MBL) and efflux-mediated mechanisms in confer- ring carbapenem resistance in nosocomial isolates of P. aeruginosa. METHODS We analyzed carbapenem nonsusceptible nosocomial P. aeruginosa isolates obtained from pediatric and adult patients at three hospitals in Moscow in 2012-2015. Carbapenem susceptibility was assessed using the E-test. In addition, minimal inhibitory concentrations (MICs) of meropenem were tested by the broth microdilution method. The presence of MBL was determined using the ED TA-mediated suppression test. Efflux-dependent resistance was measured using an assay based on MIC modification by an ionophore carbonyl cyanide 3-chlorophenyl hydrazine (CCCP). RESULTS A total of 54 carbapenem nonsusceptible P. aeruginosa isolates was examined. The presence of an MBL was detected in 37 (69%) isolates, 29 (54%) isolates had efflux-mediated resistance. In 10 (19%) isolates neither MBL nor efflux activity was found. Five out of 6 isolates (83%) with highly active efflux were MBL-positive. Among isolates with low efflux activity, 74% (17/23) possessed MBL, whereas in isolates with no efflux the rate of MBL-positivity was 60% (15/25). CONCLUSION The prevalence of MBL- and efflux-mediated carbapenem resistance in nosocomial P. aeruginosa is high. Moreover, our results reveal that several resistance mechanisms may combine at the isolate level. These data may contribute to the development of novel strategies in combating carbapenem resistance.
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