高毒力肺炎克雷伯菌耐药性和治疗策略研究进展

doi:10.3969/j.issn.1673-8640.2023.01.018

摘要/Abstract

摘要：

近30年来，高毒力肺炎克雷伯菌（hvKP）的检出率不断增加。以往学者们曾一度认为高毒力与耐药性不会在同一株肺炎克雷伯菌（KP）中重叠出现，但近年来hvKP耐药甚至多重耐药的报道越来越多，hvKP的高毒力及其与高耐药性的结合很可能会成为临床面临的重大挑战。文章就hvKP的流行病学特征、检测方法、耐药现状和治疗策略等进行阐述，以期为临床检测和治疗hvKP感染，预防和控制多重耐药hvKP的流行提供参考。

关键词: 肺炎克雷伯菌, 毒力, 耐药, 治疗

Abstract:

In the past 30 years，hypervirulent Klebsiella pneumoniae（hvKP） isolates have been increasing. Once it was believed that the hypervirulence and high drug resistance would not occur in the same Klebsiella pneumoniae（KP） isolate. However，the recent reports on drug resistance and multi-drug resistance of hvKP isolates have emerged one after another. Therefore，the hypervirulence of hvKP and its combination with multi-drug resistance is likely to become an important clinical challenge. This review focuses on the epidemiology，determination methods，drug resistance and treatment of hvKP，in order to provide a reference for the clinical determination，treatment，prevention and control of multi-drug resistant hvKP.

Key words: Klebsiella pneumoniae, Virulence, Drug resistance, Treatment

中图分类号:

R378.2

王粟, 丁立, 姜文容, 缪应新, 张艳梅, 赵虎. 高毒力肺炎克雷伯菌耐药性和治疗策略研究进展[J]. 检验医学, 2023, 38(1): 81-86.

WANG Su, DING Li, JIANG Wenrong, MIAO Yingxin, ZHANG Yanmei, ZHAO Hu. Research progress on drug resistance and treatment strategies of hypervirulent Klebsiella pneumoniae[J]. Laboratory Medicine, 2023, 38(1): 81-86.

参考文献 48

[1]	LIAO W, LIU Y, ZHANG W. Virulence evolution,molecular mechanisms of resistance and prevalence of ST11 carbapenem-resistant Klebsiella pneumoniae in China:a review over the last 10 years[J]. J Glob Antimicrob Resist, 2020, 23:174-180. DOI URL
[2]	RUSSO T A, MARR C M. Hypervirulent Klebsiella pneumoniae[J]. Clin Microbiol Rev, 2019, 32(3):e00001-19.
[3]	SELLICK J A, RUSSO T A. Getting hypervirulent Klebsiella pneumoniae on the radar screen[J]. Curr Opin Infect Dis, 2018, 31(4):341-346. DOI URL
[4]	张慧芳, 王瑞兰. 高毒力肺炎克雷伯菌的研究进展[J]. 中华肺部疾病杂志(电子版), 2021, 14(2):253-255.
[5]	LIU Y C, CHENG D L, LIN C L. Klebsiella pneumoniae liver abscess associated with septic endophthalmitis[J]. Arch Intern Med, 1986, 146(10):1913-1916. DOI URL
[6]	蒋玉婷, 张珂, 刘唐娟, 等. 高毒力肺炎克雷伯菌毒力和耐药机制研究进展[J]. 中国感染控制杂志, 2021, 20(5):473-480.
[7]	LIN Y T, SIU L K, LIN J C, et al. Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries[J]. BMC Microbiol, 2012, 12:13. DOI
[8]	CUBERO M, GRAU I, TUBAU F, et al. Hypervirulent Klebsiella pneumoniae clones causing bacteraemia in adults in a teaching hospital in Barcelona,Spain(2007-2013)[J]. Clin Microbiol Infect,2016, 22(2):154-160. DOI URL
[9]	IKEDA M, MIZOGUCHI M, OSHIDA Y, et al. Clinical and microbiological characteristics and occurrence of Klebsiella pneumoniae infection in Japan[J]. Int J Gen Med, 2018, 11:293-299.
[10]	LI W, SUN G, YU Y, et al. Increasing occurrence of antimicrobial-resistant hypervirulent(hypermucoviscous) Klebsiella pneumoniae isolates in China[J]. Clin Infect Dis, 2014, 58(2):225-232. DOI URL
[11]	ZHANG Y, ZHAO C, WANG Q, et al. High prevalence of hypervirulent Klebsiella pneumoniae infection in China:geographic distribution,clinical characteristics,and antimicrobial resistance[J]. Antimicrob Agents Chemother, 2016, 60(10):6115-6120. DOI URL
[12]	GUO Y, WANG S, ZHAN L, et al. Microbiological and clinical characteristics of hypermucoviscous Klebsiella pneumoniae isolates associated with invasive infections in China[J]. Front Cell Infect Microbiol, 2017, 7:24.
[13]	FIERER J, WALLS L, CHU P. Recurring Klebsiella pneumoniae pyogenic liver abscesses in a resident of San Diego,California,due to a K1 strain carrying the virulence plasmid[J]. J Clin Microbiol, 2011, 49(12):4371-4373. DOI URL
[14]	YE M, TU J, JIANG J, et al. Clinical and genomic analysis of liver abscess-causing Klebsiella pneumoniae identifies new liver abscess-associated virulence genes[J]. Front Cell Infect Microbiol, 2016, 6:165.
[15]	TAN T Y, CHENG Y, ONG M, et al. Performance characteristics and clinical predictive value of the string test for detection of hepato-virulent Klebsiella pneumoniae isolated from blood cultures[J]. Diagn Microbiol Infect Dis, 2014, 78(2):127-128. DOI URL
[16]	SHI Q, LAN P, HUANG D, et al. Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage[J]. BMC Microbiol, 2018, 18(1):94. DOI
[17]	RUSSO T A, OLSON R, FANG C T, et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae[J]. J Clin Microbiol, 2018, 56(9):e00776-18.
[18]	LIN Y T, WANG Y P, WANG F D, et al. Community-onset Klebsiella pneumoniae pneumonia in Taiwan:clinical features of the disease and associated microbiological characteristics of isolates from pneumonia and nasopharynx[J]. Front Microbiol, 2015, 9:122. DOI URL
[19]	WU H, LI D, ZHOU H, et al. Bacteremia and other body site infection caused by hypervirulent and classic Klebsiella pneumoniae[J]. Microb Pathog, 2017, 104:254-262. DOI URL
[20]	HUANG Y, LI J, GU D, et al. Rapid detection of k1 hypervirulent Klebsiella pneumoniae by MALDI-TOF MS[J]. Front Microbiol, 2015, 6:1435.
[21]	YU F, LV J, NIU S, et al. Multiplex PCR analysis for rapid detection of Klebsiella pneumoniae carbapenem-resistant(sequence type 258 [ST258] and ST11) and hypervirulent(ST23,ST65,ST86,and ST375) strains[J]. J Clin Microbiol, 2018, 56(9):e00731-18.
[22]	FENG Y, LU Y, YAO Z, et al. Carbapenem-resistant hypervirulent Klebsiella pneumoniae of sequence type 36[J]. Antimicrob Agents Chemother, 2018, 62(7):e02644-17.
[23]	LAM M M C, WYRES K L, DUCHÊNE S, et al. Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination[J]. Nat Commun, 2018, 9(1):2703. DOI
[24]	ZHANG R, LIN D, CHAN E W, et al. Emergence of carbapenem-resistant serotype K1 hypervirulent Klebsiella pneumoniae strains in China[J]. Antimicrob Agents Chemother, 2015, 60(1):709-711. DOI URL
[25]	DONG N, YANG X, ZHANG R, et al. Tracking microevolution events among ST11 carbapenemase-producing hypervirulent Klebsiella pneumoniae outbreak strains[J]. Emerg Microbes Infect, 2018, 7(1):146.
[26]	XIE Y, TIAN L, LI G, et al. Emergence of the third-generation cephalosporin-resistant hypervirulent Klebsiella pneumoniae due to the acquisition of a self-transferable blaDHA-1-carrying plasmid by an ST23 strain[J]. Virulence, 2018, 9(1):838-844. DOI URL
[27]	GU D, DONG N, ZHENG Z, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital:a molecular epidemiological study[J]. Lancet Infect Dis, 2018, 18(1):37-46. DOI URL
[28]	贾艳增, 时东彦. 替加环素与临床常用抗生素对碳青霉烯耐药高毒力肺炎克雷伯菌体外联合药敏试验[J]. 现代检验医学杂志, 2021, 36(3):113-117.
[29]	ZHAO Y, ZHANG S, FANG R, et al. Dynamic epidemiology and virulence characteristics of carbapenem-resistant Klebsiella pneumoniae in Wenzhou,China from 2003 to 2016[J]. Infect Drug Resist, 2020, 13:931-940. DOI URL
[30]	LIU Y Y, WANG Y, WALSH T R, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China:a microbiological and molecular biological study[J]. Lancet Infect Dis, 2016, 16(2):161-168. DOI URL
[31]	LU Y, FENG Y, MCNALLY A, et al. The occurence of colistin-resistant hypervirulent Klebsiella pneumoniae in China[J]. Front Microbiol, 2018, 9:2568. DOI URL
[32]	HUANG Y H, CHOU S H, LIANG S W, et al. Emergence of an XDR and carbapenemase-producing hypervirulent Klebsiella pneumoniae strain in Taiwan[J]. J Antimicrob Chemother, 2018, 73(8):2039-2046. DOI URL
[33]	黄祺, 田李星, 周晓英, 等. 多重耐药菌现状及临床治疗策略研究进展[J]. 中国中西医结合急救杂志, 2017, 24(3):328-332.
[34]	HAO M, SHI X, LV J, et al. In vitro activity of apramycin against carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates[J]. Front Microbiol, 2020, 11:425. DOI URL
[35]	MAMUN M M, SORINOLU A J, MUNIR M, et al. Nanoantibiotics:functions and properties at the nanoscale to combat antibiotic resistance[J]. Front Chem, 2021, 9:687660. DOI URL
[36]	WANG Y, DING X, CHEN Y, et al. Antibiotic-loaded,silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections[J]. Biomaterials, 2016, 101:207-216. DOI URL
[37]	秦社宣, 邵永珍, 王燕, 等. 新型纳米银对产ESBLs肺炎克雷伯菌的抑制作用[J]. 中国新药杂志, 2017, 26(22):2737-2741.
[38]	SCHMIDT C. Phage therapy's latest makeover[J]. Nat Biotechnol, 2019, 37(6):581-586. DOI PMID
[39]	周铁丽, 徐雯雅. 抗菌治疗中噬菌体与抗菌药物联合使用的研究进展及前景[J]. 浙江医学, 2021, 43(7):691-695.
[40]	田而慷, 王玥, 吴卓轩, 等. 噬菌体疗法:回顾与展望[J]. 四川大学学报(医学版), 2021, 52(2):170-175.
[41]	VERMA V, HARJAI K, CHHIBBER S. Restricting ciprofloxacin-induced resistant variant formation in biofilm of Klebsiella pneumoniae B5055 by complementary bacteriophage treatment[J]. J Antimicrob Chemother, 2009, 64(6):1212-1218. DOI URL
[42]	WITTEBOLE X, DE ROOCK S, OPAL S M. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens[J]. Virulence, 2014, 5(1):226-235. DOI PMID
[43]	PELFRENE E, WILLEBRAND E, CAVALEIRO SANCHES A, et al. Bacteriophage therapy:a regulatory perspective[J]. J Antimicrob Chemother, 2016, 71(8):2071-2074. DOI URL
[44]	LIN T L, HSIEH P F, HUANG Y T, et al. Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae:implication in typing and treatment[J]. J Infect Dis, 2014, 210(11):1734-1744. DOI URL
[45]	FOLLADOR R, HEINZ E, WYRES K L, et al. The diversity of Klebsiella pneumoniae surface polysaccharides[J]. Microb Genom, 2016, 2(8):e000073.
[46]	FELDMAN M F, MAYER BRIDWELL A E, SCOTT N E, et al. A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae[J]. Proc Natl Acad Sci U S A, 2019, 116(37):18655-18663. DOI URL
[47]	HSIEH P F, LIN T L, YANG F L, et al. Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess[J]. PLoS One, 2012, 7(3):e33155. DOI URL
[48]	DIAGO-NAVARRO E, CALATAYUD-BASELGA I, SUN D, et al. Antibody-based immunotherapy to treat and prevent infection with hypervirulent Klebsiella pneumoniae[J]. Clin Vaccine Immunol, 2017, 24(1):e00456-16.