Outbreak by Hypermucoviscous Klebsiella pneumoniae ST11 Isolates with Carbapenem Resistance in a Tertiary Hospital in China

Lingling Zhan, Shanshan Wang, Yinjuan Guo, Ye Jin, Jingjing Duan, Zhihao Hao, Jingnan Lv, Xiuqin Qi, Longhua Hu, Liang Chen, Barry N Kreiswirth, Rong Zhang, Jingye Pan, Liangxing Wang, Fangyou Yu, Lingling Zhan, Shanshan Wang, Yinjuan Guo, Ye Jin, Jingjing Duan, Zhihao Hao, Jingnan Lv, Xiuqin Qi, Longhua Hu, Liang Chen, Barry N Kreiswirth, Rong Zhang, Jingye Pan, Liangxing Wang, Fangyou Yu

Abstract

Hypervirulent and multidrug resistant Klebsiella pneumoniae strains pose a significant threat to the public health. In the present study, 21 carbapenem-resistant K. pneumoniae isolates (CRKP) were determined by the string test as hypermucoviscous K. pneumoniae (HMKP), with the prevalence of 15.0% (21/140) among CRKP, and 1.1% (21/1838) among all K. pneumoniae isolates. Among them, 7 (33.3%), and 1 (4.76%) isolate belonged to capsular serotype K20 and K2 respectively, while 13 (61.9%, 13/21) weren't successfully typed by capsular serotyping. All the 21 isolates were carbapenemase-producers and were positive for blaKPC-2. In addition to blaKPC-2, all the 21 isolates except one harbor blaSHV-11, and 15 carry extended-spectrum β-lactamase gene blaCTX-M-65. The virulence-associated genes with more than 90% of positive rates among 21 isolates included ureA (100%, 21/21), wabG (100%, 21/21), fimH (95.2%, 20/21), entB (95.2%, 20/21), ycf (95.2%, 20/21), ybtS (95.2%, 20/21), and iutA (90.5%, 19/21). rmpA and aerobactin were found in 57.1% (12/21) isolates. Five sequence types (STs) were identified by multilocus sequence typing (MLST), including ST11 (11 K-non capsule typable and 5 K20 isolates), ST268 (1 K20 isolate and 1 K-non capsule typable isolate), ST65 (1 K2 isolate), ST692 (1 K-non capsule typable isolate), and ST595, a novel sequence type (1 K-non capsule typable isolate). Pulsed-field gel electrophoresis (PFGE) results showed two major PFGE clusters, of which cluster A accounts for 6 ST11 isolates (28.6%) and cluster B includes 8 ST11 isolates (38.1%, 8/21). Ten and six ST11 isolates were isolated from 2014 and 2015, respectively, while 8 were isolated from the same month of December in 2014. Ten isolates were collected from the intensive care unit (ICU), and all except one belonged to ST11. Additional 4 ST11 isolates were collected from patients in non-ICU wards, who had more than 10 days of ICU stay history in 2014 prior to transfer to their current wards where the isolates were recovered. Taken together, the present study showed a hospital outbreak and dissemination of ST11 HMKP with carbapenem resistance caused by KPC-2. Effective surveillance and strict infection control strategies should be implemented to prevent outbreak by HMKP with carbapenem resistance in hospitals.

Keywords: KPC-2; Klesiella pneumoniae; carbapenem resistance; epidemiology; hypermucoviscous.

Figures

Figure 1
Figure 1
PFGE results for 21 carbapenem-resistant HMKP isolates.

References

    1. Bialek-Davenet S., Criscuolo A., Ailloud F., Passet V., Jones L., Delannoy-Vieillard A. S., et al. . (2014). Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg. Infect. Dis. 20, 1812–1820. 10.3201/eid2011.140206
    1. Candan E. D., Aksoz N. (2015). Klebsiella pneumoniae: characteristics of carbapenem resistance and virulence factors. Acta Biochim. Polonica 62, 867–874. 10.18388/abp.2015_1148
    1. Cheng D. L., Liu Y. C., Yen M. Y., Liu C. Y., Wang R. S. (1991). Septic metastatic lesions of pyogenic liver abscess. Their association with Klebsiella pneumoniae bacteremia in diabetic patients. Arch. Intern. Med. 151, 1557–1559. 10.1001/archinte.1991.00400080059010
    1. Chuang Y. P., Fang C. T., Lai S. Y., Chang S. C., Wang J. T. (2006). Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J. Infect. Dis. 193, 645–654. 10.1086/499968
    1. Chung D. R., Lee H. R., Lee S. S., Kim S. W., Chang H. H., Jung S. I., et al. . (2008). Evidence for clonal dissemination of the serotype K1 Klebsiella pneumoniae strain causing invasive liver abscesses in Korea. J. Clin. Microbiol. 46, 4061–4063. 10.1128/JCM.01577-08
    1. CLSI (2016). Performance Standards for Antimicrobial Susceptibility Testing, 26th Informational Supplement (M100-S26). Wayne, PA: Clinical and Laboratory Standards Institute.
    1. Diancourt L., Passet V., Verhoef J., Grimont P. A., Brisse S. (2005). Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J. Clin. Microbiol. 43, 4178–4182. 10.1128/JCM.43.8.4178-4182.2005
    1. Fang C. T., Chuang Y. P., Shun C. T., Chang S. C., Wang J. T. (2004). A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J. Exp. Med. 199, 697–705. 10.1084/jem.20030857
    1. Fang C. T., Lai S. Y., Yi W. C., Hsueh P. R., Liu K. L., Chang S. C. (2007). Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin. Infect. Dis. 45, 284–293. 10.1086/519262
    1. Fang F. C., Sandler N., Libby S. J. (2005). Liver abscess caused by magA+ Klebsiella pneumoniae in North America. J. Clin. Microbiol. 43, 991–992. 10.1128/JCM.43.2.991-992.2005
    1. Jiang X., Ni Y., Jiang Y., Yuan F., Han L., Li M., et al. . (2005). Outbreak of infection caused by Enterobacter cloacae producing the novel VEB-3 beta-lactamase in China. J. Clin. Microb. 43, 826–831. 10.1128/JCM.43.2.826-831.2005
    1. Li H., Zhang J., Liu Y., Zheng R., Chen H., Wang X., et al. (2014). Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: predominance of KPC-2 enzyme. Diagn. Microbiol. Infect. Dis. 78, 63–65. 10.1016/j.diagmicrobio.2013.10.002
    1. Li W., Sun G., Yu Y., Li N., Chen M., Jin R., et al. . (2014). Increasing occurrence of antimicrobial-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in China. Clin. Infect. Dis. 58, 225–232. 10.1093/cid/cit675
    1. Liao C. H., Huang Y. T., Chang C. Y., Hsu H. S., Hsueh P. R. (2014). Capsular serotypes and multilocus sequence types of bacteremic Klebsiella pneumoniae isolates associated with different types of infections. Eur. J. Clin. Microbiol. Infect. Dis. 33, 365–369. 10.1007/s10096-013-1964-z
    1. Lin Y. T., Jeng Y. Y., Chen T. L., Fung C. P. (2010). Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: clinical and microbiological characteristics in Taiwan, 2001-2008. BMC infect. Dis. 10:307. 10.1186/1471-2334-10-307
    1. Lin Y. T., Wang Y. P., Wang F. D., Fung C. P. (2015). Community-onset Klebsiella pneumoniae pneumonia in Taiwan: clinical features of the disease and associated microbiological characteristics of isolates from pneumonia and nasopharynx. Front. Microbiol. 9:122. 10.3389/fmicb.2015.00122
    1. Liu Y. C., Cheng D. L., Lin C. L. (1986). Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch. Int. Med. 146, 1913–1916. 10.1001/archinte.1986.00360220057011
    1. Liu Y. M., Li B. B., Zhang Y. Y., Zhang W., Shen H., Li H., et al. . (2014). Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China. Antimicrob. Agents Chemother. 58, 5379–5385. 10.1128/AAC.02523-14
    1. Pagani L., Dell'Amico E., Migliavacca R., D'Andrea M. M., Giacobone E., Amicosante G., et al. . (2003). Multiple CTX-M-type extended-spectrum beta-lactamases in nosocomial isolates of Enterobacteriaceae from a hospital in northern Italy J. Clin. Microb. 41, 4264–4269. 10.1128/JCM.41.9.4264-4269.2003
    1. Prokesch B. C., TeKippe M., Kim J., Raj P., TeKippe E. M., Greenberg D. E. (2016). Primary osteomyelitis caused by hypervirulent Klebsiella pneumoniae. Lancet Infect. Dis. 16, e190–e195. 10.1016/S1473-3099(16)30021-4
    1. Qi Y., Wei Z., Ji S., Du X., Shen P., Yu Y. (2011). ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J. Antimicrob. Chemother. 66, 307–312. 10.1093/jac/dkq431
    1. Qu T. T., Zhou J. C., Jiang Y., Shi K. R., Li B., Shen P., et al. . (2015). Clinical and microbiological characteristics of Klebsiella pneumoniae liver abscess in East China. BMC Infect. Dis. 15:161. 10.1186/s12879-015-0899-7
    1. Russo T. A., Olson R., Macdonald U., Metzger D., Maltese L. M., Drake E. J., et al. . (2014). Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect. Immun. 82, 2356–2367. 10.1128/IAI.01667-13
    1. Shon A. S., Bajwa R. P., Russo T. A. (2013). Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence 4, 107–118. 10.4161/viru.22718
    1. Siu L. K., Yeh K. M., Lin J. C., Fung C. P., Chang F. Y. (2012). Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect. Dis. 12, 881–887. 10.1016/S1473-3099(12)70205-0
    1. Struve C., Roe C. C., Stegger M., Stahlhut S. G., Hansen D. S., Engelthaler D. M., et al. . (2015). Mapping the evolution of hypervirulent Klebsiella pneumoniae. MBio 6:e00630. 10.1128/mBio.00630-15
    1. Tenover F. C., Arbeit R. D., Goering R. V., Mickelsen P. A., Murray B. E., Persing D. H., et al. . (1995). Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J. Clin. Microb. 33, 2233–2239.
    1. Turton J. F., Englender H., Gabriel S. N., Turton S. E., Kaufmann M. E., Pitt T. L. (2007). Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents. J. Med. Microbiol. 56(Pt 5), 593–597. 10.1099/jmm.0.46964-0
    1. Turton J. F., Perry C., Elgohari S., Hampton C. V. (2010). PCR characterization and typing of Klebsiella pneumoniae using capsular type-specific, variable number tandem repeat and virulence gene targets. J. Med. Microbiol. 59(Pt 5), 541–547. 10.1099/jmm.0.015198-0
    1. Validi M., Soltan Dallal M. M., Douraghi M., Fallah Mehrabadi J., Rahimi Foroushani A. (2016). Identification of Klebsiella pneumoniae Carbapenemase-producing Klebsiella oxytoca in Clinical Isolates in Tehran Hospitals, Iran by Chromogenic Medium and Molecular Methods. Osong Public Health Res. Perspect. 7, 301–306. 10.1016/j.phrp.2016.08.006
    1. Wang J. H., Liu Y. C., Lee S. S., Yen M. Y., Chen Y. S., Wang J. H., et al. (1998). Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin. Infect. Dis. 26, 1434–1438.
    1. Yan J. J., Zheng P. X., Wang M. C., Tsai S. H., Wang L. R., Wu J. J. (2015). Allocation of Klebsiella pneumoniae Bloodstream Isolates into four distinct groups by ompK36 typing in a Taiwanese University Hospital. J. Clin. Microb. 53, 3256–3263. 10.1128/JCM.01152-15
    1. Yan Q., Zhou M., Zou M., Liu W. E. (2016). Hypervirulent Klebsiella pneumoniae induced ventilator-associated pneumonia in mechanically ventilated patients in China. Eur. J. Clin. Microbiol. Infect. Dis. 35, 387–396. 10.1007/s10096-015-2551-2
    1. Yang Z., Liu W., Cui Q., Niu W., Li H., Zhao X., et al. . (2014). Prevalence and detection of Stenotrophomonas maltophilia carrying metallo-beta-lactamase blaL1 in Beijing, China. Front. Microbiol. 5:692. 10.3389/fmicb.2014.00692
    1. Yao B., Xiao X., Wang F., Zhou L., Zhang X., Zhang J. (2015). Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China. Int. J. Infect. Dis. 37, 107–112. 10.1016/j.ijid.2015.06.023
    1. Yu W. L., Ko W. C., Cheng K. C., Lee C. C., Lai C. C., Chuang Y. C. (2008). Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn. Microbiol. Infect. Dis. 62, 1–6. 10.1016/j.diagmicrobio.2008.04.007
    1. Yu W. L., Ko W. C., Cheng K. C., Lee H. C., Ke D. S., Lee C. C., et al. . (2006). Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin. Infect. Dis. 42, 1351–1358. 10.1086/503420
    1. Zhang R., Lin D., Chan E. W., Gu D., Chen G. X., Chen S. (2015). Emergence of Carbapenem-Resistant Serotype K1 Hypervirulent Klebsiella pneumoniae strains in China. Antimicrob. Agents Chemother. 60, 709–711. 10.1128/AAC.02173-15
    1. Zhang Y., Zeng J., Liu W., Zhao F., Hu Z., Zhao C., et al. . (2015). Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate from clinical infections in China. J. Infect. 71, 553–560. 10.1016/j.jinf.2015.07.010
    1. Zhang Y., Zhao C., Wang Q., Wang X., Chen H., Li H., et al. . (2016). High prevalence of hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics and antimicrobial resistance. Antimicrob. Agents Chemother. 60, 6115–620. 10.1128/AAC.01127-16

Source: PubMed

Подписаться