Zhao Jin, Liu Yunxi, Liu Yi, Wang Dong, Ni Wentao, Wang Rui, Liu Youning, Zhang Bo
Department of Pulmonary and Critical Care Medicine, Air Force General Hospital of PLA, Beijing, China.
Department of Infection Management and Disease Control, Chinese PLA General Hospital, Beijing, China.
Front Microbiol. 2018 Mar 26;9:549. doi: 10.3389/fmicb.2018.00549. eCollection 2018.
is an emerging nosocomial pathogen with high resistance to most clinically used antimicrobials. Tigecycline is a potential alternative antimicrobial for infection treatment, but its resistance mechanism in clinical isolates is not fully elucidated. We investigated the antimicrobial susceptibility of 450 isolated during 2012-2015 from three university hospitals in Beijing, China. These strains exhibited high susceptibility to minocycline (98.44%), sulfamethoxazole/trimethoprim (87.56%), tigecycline (77.78 %), doxycycline (81.33%), levofloxacin (67.56%), and ticarcillin/clavulanate (73.00%). The susceptibility of tigecycline-nonsusceptible strains (TNS) to doxycycline and levofloxacin was much lower than that of tigecycline-susceptible strains (TSS) (25.00% vs. 97.71% for doxycycline, < 0.001; 17.00% vs. 82.00% for levofloxacin, < 0.001). We further selected 48 TNS and TSS and compared the detection rate of eight tetracycline-specific genes by PCR and the expression level of six intrinsic multidrug resistance efflux pumps by real-time PCR. Only one and two genes in TNS and three genes in TSS were detected, and the detection rate had no difference. The average expression level of in TNS was higher than that in TSS [20.59 (11.53, 112.54) vs. 2.07 (0.80, 4.96), < 0.001], while the average expression levels of , , , , and were not significantly different, indicating that was the predominant resistance genetic determinant in clinical . Higher expression was also observed in levofloxacin- and doxycycline-nonsusceptible isolates than in their corresponding susceptible isolates [16.46 (5.83, 102.24) vs. 2.72 (0.80, 6.25) for doxycycline, < 0.001; 19.69 (8.07, 115.10) vs. 3.01(1.00, 6.03), < 0.001], indicating that was also the resistance genetic determinant to levofloxacin and doxycycline. The consistent resistance profile and common resistance genetic determinant highlight the importance of rational use of tigecycline for preventing the occurrence and spread of multidrug resistance.
是一种新兴的医院病原体,对大多数临床使用的抗菌药物具有高度耐药性。替加环素是治疗感染的一种潜在替代抗菌药物,但其在临床分离株中的耐药机制尚未完全阐明。我们调查了2012年至2015年期间从中国北京的三家大学医院分离出的450株的抗菌药敏情况。这些菌株对米诺环素(98.44%)、磺胺甲恶唑/甲氧苄啶(87.56%)、替加环素(77.78%)、强力霉素(81.33%)、左氧氟沙星(67.56%)和替卡西林/克拉维酸(73.00%)表现出高敏感性。替加环素不敏感菌株(TNS)对强力霉素和左氧氟沙星的敏感性远低于替加环素敏感菌株(TSS)(强力霉素为25.00%对97.71%,<0.001;左氧氟沙星为17.00%对82.00%,<0.001)。我们进一步选择了48株TNS和TSS,通过PCR比较了8个四环素特异性基因的检出率,并通过实时PCR比较了6个内在多药耐药外排泵的表达水平。TNS中仅检测到1个基因,TSS中检测到2个基因,检出率无差异。TNS中 的平均表达水平高于TSS [20.59(11.53,112.54)对2.07(0.80,4.96),<0.001],而 、 、 、 和 的平均表达水平无显著差异,表明 在临床 中是主要的耐药基因决定因素。在左氧氟沙星和强力霉素不敏感分离株中也观察到 表达高于其相应的敏感分离株 [强力霉素为16.46(5.83,102.24)对2.72(0.80,6.25),<0.001;左氧氟沙星为19.69(8.07,115.10)对3.01(1.00,6.03),<0.001],表明 也是对左氧氟沙星和强力霉素的耐药基因决定因素。一致的耐药谱和共同的耐药基因决定因素突出了合理使用替加环素以预防多药耐药的发生和传播的重要性。