摘要
肺炎克雷伯菌(Klebsiella pneumoniae,KP)常引发临床细菌性感染,其对抗生素的异质性耐药(heteroresistance,HR)经常导致治疗失败。研究KP对头孢菌素类抗生素的异质性耐药情况,可为治疗KP感染提供参考。收集100株临床分离的KP,采用微量肉汤稀释法、Kirby-Bauer(K-B)药敏纸片法、菌群谱型分析法(population analysis profile,PAP)、耐药稳定性试验以及适应成本试验探究KP的异质性耐药特征。微量肉汤稀释法测定KP对头孢他啶(ceftazidime,CAZ)和头孢吡肟(cefepime,FEP)的耐药率分别为23%和25%。K-B药敏纸片法初筛得到KP对CAZ和FEP的异质性耐药率为33%和23%。PAP试验复筛确认了9株FEP异质性耐药菌株,检出率为9%,耐药亚群发生频率为1×10^(-6)~4×10^(-2)。在无抗生素条件下传代50代后,异质性耐药菌株KS38耐药亚群的耐药水平发生部分回复,异质性耐药菌株KR9耐药亚群的耐药水平保持稳定。适应成本试验结果表明,KS38耐药亚群比原始菌株生长速度快(4~8 h),且有显著差异(P<0.05),KR9耐药亚群和亲本菌株的生长速率之间均无统计学差异(P>0.05)。肺炎克雷伯菌对头孢菌素类抗生素的异质性耐药率相对偏低,但耐药亚群的发生频率较高。耐药亚群的稳定性不同,但经过50代传代后都保持在临床耐药水平,均未产生生长适应成本。因此在用头孢菌素治疗KP感染时要注意HR的发生,防止出现更高水平的耐药亚群,导致治疗失败。
Klebsiella pneumoniae(KP)often causes clinical bacterial infections,and its heteroresistance(HR)to antibiotics often leads to treatment failure.To provide a reference for the clinical treatment of bacterial infections,the heteroresistance of K.pneumoniae to cephalosporin antibiotics was studied in this article.Collect 100 clinical isolates of K.pneumoniae.Heteroresistance characteristics of KP were investigated by the microdilutionbroth method,Kirby Bauer(K-B)disk diffusion method,population analysis profile(PAP),resistance stability test,and fitness cost experiment.The resistance rates of KP to Ceftazidime(CAZ)and Cefepime(FEP)were 23%and 25%,respectively,determined by the microdilution broth method.According to the K-B method,the heteroresistance rates of KP to CAZ and FEP were 33%and 23%,respectively.The PAP test confirmed nine FEP heteroresistant strains,accounting for 9%of the total experimental strains.The frequency of resistant subpopulations was 1×10^(-6)-4×10^(-2).After 50 generations of passage without antibiotic pressure,the resistance level of the heteroresistant strain KS38 resistant subpopulations reverted to a certain degree,while the resistance level of the heteroresistant strain KR9 resistant subpopulations remained stable.The fitness cost experimental results showed that the KS38 resistant subpopulations grew faster than the parental strain(4-8 h),with significant differences(P<0.05).There was no statistical difference(P>0.05)in the growth rates of heteroresistance subpopulations of KR9 and its parental strain.In this study,the heteroresistance rate of K.pneumoniae to cephalosporin antibiotics was relatively low,but the frequency of resistant subpopulations was relatively high.The resistance levels of the resistant subpopulations remain at clinical resistance levels after passage for 50 generations,though their resistant stability varies.Moreover,the resistant subpopulations did not show fitness costs.Therefore,to prevent the emergence of higher levels of resistance bacterial subpopulations that lead to clinical treatment failure,more attention should be paid to the occurrence of heteroresistance when using cephalosporin antibiotics for the treatment of K.pneumoniae infections.
作者
史梦兰
李文茹
朱爱意
张建设
谢小保
SHI Menglan;LI Wenru;ZHU Aiyi(National Engineering Research Center for Marine Aquaculture of Zhejiang Ocean University,Zhoushan 316022;Key Laboratory of Agricultural Microbiomics and Precision Application(MARA),Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application,Key Laboratory of Agricultural Microbiome(MARA),State Key Laboratory of Applied Microbiology Southern China,Institute of Microbiology,Guangdong Academy of Sciences,Guangzhou 510070,China)
出处
《浙江海洋大学学报（自然科学版）》
CAS
2024年第3期268-276,共9页
Journal of Zhejiang Ocean University：Natural Science
基金
广东省基础与应用基础研究项目(2021A1515011080)。
