我们确定了四种氨基糖苷的体外敏感性,它们不是针对耐碳青霉烯的肠杆菌科(CRE)集合的4,6-二取代的脱氧链霉胺(DOS)亚类。从中国多家医院收集CRE临床菌株(n=134),并携带blaNDM(blaNDM-1,blaNDM-5或blaNDM-7;n=66),blaKPC-2(n=62)或blaIMP-4(n=7;包括携带blaNDM-1和blaIMP-4的一个)。新霉素的MIC,巴龙霉素,链霉素和阿普霉素以及三种4,6-二取代的DOS氨基糖苷(阿米卡星,庆大霉素和妥布霉素)是使用具有临床实验室标准研究所(对于阿米卡星,庆大霉素和妥布霉素),美国食品和药物管理局(链霉素),国家抗菌素耐药性监测系统(阿普霉素)或法国微生物协会(新霉素和巴龙霉素)。使用IlluminaX10平台对安普霉素抗性菌株进行全基因组测序。在CRE菌株中,65.7、64.9、79.1和95.5%对新霉素敏感(MIC50/MIC90,8/256μg/ml),巴龙霉素(4/>256μg/ml),链霉素(16/256μg/ml)和安普霉素(4/8μg/ml),分别,而只有55.2、28.4和35.1%对阿米卡星(32/>256μg/ml)敏感,庆大霉素(128/>256μg/ml)和妥布霉素(64/>256μg/ml),分别。6株CRE菌株包括5株不同序列类型的大肠埃希菌和1株肺炎克雷伯菌对阿普霉素耐药,在所有这些菌株中均检测到阿普霉素耐药基因aac(3)-IVa。总之,新霉素,巴龙霉素,链霉素和安普霉素保留对大多数CRE菌株的活性。尽管目前这些非4,6-二取代的DOS氨基糖苷类都不适合人体静脉内使用,这些药物需要对CRE感染进行进一步的研究。
We determined the in vitro susceptibility of four aminoglycosides, which are not of the 4,6-disubstituted deoxystreptamine (DOS) subclass against a collection of carbapenem-resistant Enterobacteriaceae (CRE). CRE clinical strains (n = 134) were collected from multiple hospitals in
China and carried blaNDM (blaNDM-1, blaNDM-5 or blaNDM-7; n = 66), blaKPC-2 (n = 62) or blaIMP-4 (n = 7; including one carrying blaNDM-1 and blaIMP-4). MICs of neomycin,
paromomycin, streptomycin and apramycin as well as three 4,6-disubstituted DOS aminoglycosides (amikacin, gentamicin and tobramycin) were determined using the broth microdilution with breakpoints defined by the Clinical Laboratory Standards Institute (for amikacin, gentamicin and tobramycin), US Food and Drug Administration (streptomycin), the National Antimicrobial Resistance Monitoring System (apramycin) or la Société Française de Microbiologie (neomycin and
paromomycin). Apramycin-resistant strains were subjected to whole genome sequencing using Illumina X10 platform. Among CRE strains, 65.7, 64.9, 79.1, and 95.5% were susceptible to neomycin (MIC50/MIC90, 8/256 μg/ml),
paromomycin (4/>256 μg/ml), streptomycin (16/256 μg/ml) and apramycin (4/8 μg/ml), respectively, while only 55.2, 28.4, and 35.1% were susceptible to amikacin (32/>256 μg/ml), gentamicin (128/>256 μg/ml) and tobramycin (64/>256 μg/ml), respectively. Six CRE strains including five Escherichia coli of different sequence types and one Klebsiella pneumoniae were resistant to apramycin and the apramycin-resistant gene aac(3)-IVa was detected in all of these strains. In conclusion, neomycin,
paromomycin, streptomycin and apramycin retain activity against most CRE strains. Although none of these non-4,6-disubstituted DOS aminoglycosides are suitable for intravenous use in human at present, these agents warrant further investigations to be used against CRE infections.