目的 旨在对比重症监护室（ICU）中碳青霉烯类耐药肺炎克雷伯菌（CRKP）与碳青霉烯敏感肺炎克雷伯菌（CSKP）在耐药性、毒力及基因组方面的差异，为理解CRKP流行特征、优化治疗策略及开发防控措施提供科学依据。方法 以2019年1月至2024年1月从本院ICU细菌培养分离的260株非重复肺炎克雷伯菌（KP）（包含CRKP（150株）及CSKP（110株））为研究对象，比较CRKP以及CSKP药敏差异，聚合酶链反应（PCR）筛查耐药基因、毒力基因及荚膜分型，拉丝实验评估高黏表型，分析碳青霉烯类耐药高毒力肺炎克雷伯菌（CR-HVKP）基因组特征分布情况。结果 CRKP在β-内酰胺类（PIP、PSL、AMC）、碳青霉烯类（IMP、ETP、MRP）、氨基糖苷类（GM）、酰胺醇类（AMK）、喹诺酮类（CIP、LVX）、四环素类（TE）、大环内酯类（MIN）以及磺胺类（SXT）的耐药率均高于CSKP（P<0.05），CRKP菌株中金属酶类占30%，非金属酶类占66.7%，CRKP的高黏表型占22.0%，低黏表型占78.0%；CSKP的高黏表型占47.3%，低黏表型占52.7%；CSKP中毒力基因rmpA、aerobicition、magA、allS、Kfu和entB的阳性率均高于CRKP（P<0.05），ybtS在CRKP中的阳性率高于CSKP（P<0.05）。耐药基因blaKPC、blaNDM、blaVIM和blaOXA-48在CRKP中的阳性率远高于CSKP，（P<0.05）。荚膜分型K1、K2、K5、K54和K57在CSKP中的阳性率均高于CRKP（P<0.05）。结论 针对CRKP的高耐药性和复杂基因型，临床治疗需综合考虑多种因素，制定合理方案，并加强耐药性的监测与防控，以提升疗效并降低耐药性。
Abstract
Objective: to compare the differences in drug resistance, virulence, and genomics between carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolated from intensive care units (ICUs), providing scientific evidence for understanding the epidemiological characteristics of CRKP, optimizing treatment strategies, and developing preventive and control measures.Methods: From January 2019 to January 2024, a total of 260 non-duplicate strains of Klebsiella pneumoniae (KP), including 150 CRKP and 110 CSKP, isolated from bacterial cultures in our hospital's ICU were selected as the study subjects. The differences in drug sensitivity between CRKP and CSKP were compared. Polymerase chain reaction (PCR) was used to screen for drug resistance genes, virulence genes, and capsule serotypes. The string test was performed to assess the hypermucoid phenotype. The genomic characteristics and distribution of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HVKP) were analyzed.Results: The drug resistance rates of CRKP were higher than those of CSKP for β-lactams (PIP, PSL, AMC), carbapenems (IMP, ETP, MRP), aminoglycosides (GM), amphenicols (AMK), quinolones (CIP, LVX), tetracyclines (TE), macrolides (MIN), and sulfonamides (SXT) (P<0.05). Among CRKP strains, metallo-β-lactamases accounted for 30%, and non-metallo-β-lactamases accounted for 66.7%. The hypermucoid phenotype was observed in 22.0% of CRKP strains and 78.0% had a low-mucoid phenotype; for CSKP, the hypermucoid phenotype was observed in 47.3% and 52.7% had a low-mucoid phenotype. The positive rates of virulence genes rmpA, aerobicition, magA, allS, Kfu, and entB were higher in CSKP than in CRKP (P<0.05), while the positive rate of ybtS was higher in CRKP than in CSKP (P<0.05). The positive rates of drug resistance genes blaKPC, blaNDM, blaVIM, and blaOXA-48 were much higher in CRKP than in CSKP (P<0.05). The positive rates of capsule serotypes K1, K2, K5, K54, and K57 were higher in CSKP than in CRKP (P<0.05).Conclusion: Given the high drug resistance and complex genotype of CRKP, clinical treatment should consider multiple factors comprehensively, develop reasonable treatment plans, and strengthen the monitoring and prevention of drug resistance to improve therapeutic efficacy and reduce resistance.
关键词
重症监护室 /
碳青霉烯类耐药肺炎克雷伯菌 /
毒力基因 /
耐药基因 /
荚膜分型 /
分子生物学
Key words
Intensive Care Unit /
Carbapenem-resistant Klebsiella pneumoniae /
Virulence Gene /
Drug Resistance Gene /
Capsule Serotype /
Molecular Biology
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1]李冉,梁玉宜,苏歆,等.广州某三甲医院耐碳青霉烯类肺炎克雷伯菌耐药及毒力基因分析[J].国际检验医学杂志,2024,45(22):2773-2778.
[2]Yan X ,Yang M ,Ayala E J , et al.Antimicrobial resistance, virulence genes profiles and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae strains from captive giant pandas (Ailuropoda melanoleuca)[J].BMC Veterinary Research,2024,20(1):532-532.
[3]罗卓卡,王亚洲,李宝健,等.151株耐碳青霉烯类肺炎克雷伯菌临床分离株毒力基因和耐药性[J].中华医院感染学杂志,2024,34(22):3366-3370.
[4]周杰英,丁丽,彭小友,等.2020—2021年湖南省某医院分离自重症监护室的耐碳青霉烯类肺炎克雷伯菌的分子流行病学特征分析[J].中国感染与化疗杂志,2024,24(05):564-569.
[5]Kholy E T A ,Kholy E A M ,Omar H , et al.Co-existence of antibiotic resistance and virulence factors in carbapenem resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt[J].BMC Microbiology,2024,24(1):466-466.
[6]Jin L ,Ye T ,Pan X .A novel sequence type of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains from a county-level tertiary hospital in Southeastern China.[J].Medicine,2024,
103(42):e40120.
[7]Yuan Y ,Lu Y ,Cao L , et al.Genetic characteristics of clinical carbapenem-resistant Klebsiella pneumoniae: epidemic ST11 KPC-2-producing strains and non-negligible NDM-5-producing strains with diverse STs[J].Scientific Reports,2024,14(1):24296-24296.
[8]袁林玲,石路,张超,等.耐碳青霉烯类高毒力肺炎克雷伯菌形成机制的研究进展[J].临床肺科杂志,2024,29(09):1427-1433.
[9]廖全凤,张为利,邓劲,等.血液感染来源肺炎克雷伯菌毒力与碳青霉烯类耐药表型的关系及碳青霉烯类耐药高毒力菌株的鉴定[J].浙江大学学报(医学版),2024,53(04):490-497.
[10]Cheng Y ,Cheng Q ,Zhang R , et al.Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections[J].BMC Microbiology,2024,24(1):309-309.
[11]Huang Y ,Cai Y ,He W , et al.Virulence gene distribution and molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae in the ICU.[J].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences,2024,49(5):730-736.
[12]Hu F ,Pan Y ,Li H , et al.Carbapenem-resistant Klebsiella pneumoniae capsular types, antibiotic resistance and virulence factors in China: a longitudinal, multi-centre study.[J].Nature microbiology,2024,9(3):814-829.
[13]Jiang M ,Qiu X ,Shui S , et al.Differences in molecular characteristics and expression of virulence genes in carbapenem-resistant and sensitive Klebsiella pneumoniae isolates in Ningbo, China[J].Frontiers in Microbiology,2024,151356229-1356229.
[14]Liao Y ,Gong J ,Yuan X , et al.Virulence Factors and Carbapenem-Resistance Mechanisms in Hypervirulent Klebsiella Pneumoniae.[J].Infection and drug resistance,2024,171551-1559.
[15]马蒙蒙,姬经超,殷彤.2018—2022年某院高毒力碳青霉烯类耐药肺炎克雷伯菌流行病学特点及耐药性分析[J].实用预防医学,2024,31(06):754-758.
[16]阿力米热·艾买提,孙哲伟,徐庆庆,等.碳青霉烯类耐药肺炎克雷伯菌对喹诺酮类的高度耐药性及其耐药机制[J].中国感染与化疗杂志,2024,24(03):326-331.
[17]Yumei G ,Faqiang L ,Yulan Z , et al.Virulence, antimicrobial resistance, and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae in a hospital in Shijiazhuang City from China.[J].International microbiology : the official journal of the Spanish Society for Microbiology,2023,26(4):1073-1085.
[18]RibeiroZ M G ,Martins E L D ,Augusto C M , et al.Outbreak report of polymyxin-carbapenem
-resistant Klebsiella pneumoniae causing untreatable infections evidenced by synergy tests and bacterial genomes[J].Scientific Reports,2023,13(1):6238-6238.
[19]Merve Y ,Nural C .[Investigation of Virulence Genes and Carbapenem Resistance Genes in Hypervirulent and Classical Isolates of Klebsiella pneumoniae Isolated from Various Clinical Specimens].[J].Mikrobiyoloji bulteni,2023,57(2):188-206.
[20]李宜檀,林镇洲,王明贞,等.碳青霉烯类耐药肺炎克雷伯菌分子生物学特征及对头孢他啶-阿维巴坦耐药机制的初步研究[J].微生物学免疫学进展,2023,51(05):47-54
[21]韩晶,刘晶,杨自坚.医院获得性肺炎患者耐碳青霉烯类肺炎克雷伯菌分离株耐药基因及毒力因子研究[J].临床医学,2024,44(08):21-25.[4]
[22]孔娜娜,严育忠,杨德平,等.耐碳青霉烯类高毒力肺炎克雷伯菌的研究进展[J].检验医学与临床,2023,20(23):3531-3536.
