In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates
In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates
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DOI：
10.3389/fmicb.2020.00425
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发表时间：
2020-03-13
影响因子：
5.2
通讯作者：
Chen, Liang
中科院分区：
文献类型：
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作者：
Hao, Mingju;Shi, Xiaohong;Chen, Liang
目的耐碳青霉烯类肺炎克雷伯菌(CR-hvKp)的出现对公众构成重大威胁，迫切需要有效的抗菌治疗。最近的研究表明，安普霉素是一种有效的抗生素，对一系列多重耐药的病原体具有良好的活性。在这项研究中，我们评估了安普霉素对临床CR-hvKp以及碳青霉烯耐药非hvKp(CR-non-hvKp)分离株的体外抗菌活性。方法采用微量肉汤稀释法测定安普霉素、庆大霉素、阿米卡星、亚胺培南、美罗培南、多利培南、厄他培南等抗菌药物对84株CR-hvKp和40株CR-非hvKp的体外抗菌活性。多位点序列分型(MLST)、分子包膜分型(WZI测序)和耐药基因检测采用聚合酶链式反应(PCR)和Sanger测序。对选定的菌株进行了脉冲场凝胶电泳和下一代测序。结果84株CR-hvKp菌株对亚胺培南、美罗培南、多利培南和厄他培南的耐药率分别为97.6%、100%、97.6%和100%。安普霉素对CR-hvKp菌株的MIC50/MIC90为4/8微克/毫升。而对阿米卡星和庆大霉素的MIC50/MIC90为>；/>；。所有CR-hvKp菌株对头孢他啶-阿维巴坦、粘菌素和替环素敏感，MIC50/MIC90分别为0.5/1、0.25/0.5、1/1。对CR-Non-HvKp，安普霉素、庆大霉素和阿米卡星的MIC50/90分别为2/8、、和。CR-hvKp组与CR-非hvKp组的抗菌药耐药率差异无统计学意义(p>；0.05)。遗传分析表明，所有CR-hvKp分离株都含有BLA(KPC-2)，其中94%(n=79)属于ST11高危克隆。93.6%(44/47)的丁胺卡那霉素和庆大霉素耐药株携带16S rRNA甲基转移酶基因rmtB。结论安普霉素对包括阿米卡星和庆大霉素耐药株在内的CR-hvKp菌株具有较强的体外抗菌活性。需要进一步的研究来评估安普霉素作为治疗抗生素治疗CR-hvKp感染的适用性。
ObjectiveThe emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the in vitro activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates. MethodsBroth microdilution method was used to evaluate the in vitro activities of apramycin, gentamicin, amikacin, imipenem, meropenem, doripenem, ertapenem and other comparator "last-resort" antimicrobial agents, including ceftazidime-avibactam, colistin and tigecycline, against eighty-four CR-hvKp and forty CR-non-hvKp isolates collected from three Chinese hospitals. Multilocus Sequence typing (MLST), molecular capsule typing (wzi sequencing) and antimicrobial resistance genes were examined by PCR and Sanger sequencing. Pulsed-field gel electrophoresis and next generation sequencing were conducted on selected isolates. ResultsAmong the 84 CR-hvKp isolates, 97.6, 100, 97.6, and 100% were resistant to imipenem, meropenem, doripenem and ertapenem, respectively. Apramycin demonstrated an MIC50/MIC90 of 4/8 mu g/mL against the CR-hvKp isolates. In contrast, the MIC50/MIC90 for amikacin and gentamicin were >64/>64 mu g/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC50/MIC90 values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC50/90 values for apramycin, gentamicin and amikacin were 2/8, >64/>64, and >64/>64 mu g/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups (p > 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored bla(KPC-2), and 94% (n = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene rmtB. ConclusionApramycin demonstrated potent in vitro activity against CR-hvKp isolates, including those were resistant to amikacin or gentamicin. Further studies are needed to evaluate the applicability of apramycin to be used as a therapeutic antibiotic against CR-hvKp infections.