Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections
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The prevalence of hypervirulent Klebsiella pneumoniae (hvKP) is high in China, but clinical characteristics and outcomes of hvKP induced bloodstream infections (BSIs) are not clear. The purpose of the present study was to determine the risk factors and clinical outcomes of hvKP-BSIs in populations admitted in a teaching hospital of Nanjing, China. The genetic characteristics and antibiotic resistance patterns of the hvKP strains were further analyzed. A retrospective study was conducted in 143 patients with K. pneumoniae BSIs at Jinling Hospital in China from September 2015 to December 2016. A positive polymerase chain reaction (PCR) amplification of the plasmid-borne rmpA (p-rmpA) and aerobactin (iucA) was identified as hvKP. Overall, 24.5% (35/143) of K. pneumoniae isolates were hvKP. Multivariate analysis implicated diabetes mellitus (OR = 3.356) and community-acquired BSIs (OR = 4.898) as independent risk factors for hvKP-BSIs. The 30-day mortality rate of the hvKP-BSIs group was 37.1% (13/35) compared with 40.7% (44/108) in the cKP-BSIs control group (P = 0.706). The KPC-producing isolates (OR = 2.851), underlying disease with gastrointestinal fistula (OR = 3.054), APACHE II score ≥ 15 (OR = 6.694) and Pitt bacteremia score ≥ 2 (OR = 6.232) at infection onset were independent predictors for 30-day mortality of K. pneumoniae bacteremia patients. A high percentage (57.1%, 20/35) of KPC-producing isolates was observed among hvKP strains and ST11 was dominant in hvKP strains (17/35, 48.6%). KPC-producing hvKP is emerging, indicating the importance of epidemiologic surveillance and clinical awareness of this pathogen.
KeywordsHypervirulent Klebsiella pneumoniae Bloodstream infections Klebsiella pneumoniae Carbapenemase Risk factors Molecular characteristics Mortality
This study was supported by Key Project of Jiangsu Social Development (BE2016752) and Innovation Project of Military Medicine (16CXZ006).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board Ethics Committee of Jinling Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study formal consent is not required.
This article does not contain any studies with animals performed by any of the authors.
- 2.Ocampo AM, Chen L, Cienfuegos AV, Roncancio G, Chavda KD, Kreiswirth BN, Jimenez JN (2015) A two-year surveillance in five Colombian tertiary care hospitals reveals high frequency of non-CG258 clones of carbapenem-resistant Klebsiella pneumoniae with distinct clinical characteristics. Antimicrob Agents Chemother 60(1):332–342. https://doi.org/10.1128/aac.01775-15 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Yang S, Hemarajata P, Hindler J, Li F, Adisetiyo H, Aldrovandi G, Sebra R, Kasarskis A, MacCannell D, Didelot X, Russell D, Rubin Z, Humphries R (2017) Evolution and transmission of carbapenem-resistant Klebsiella pneumoniae expressing the blaOXA-232 gene during an institutional outbreak associated with endoscopic retrograde cholangiopancreatography. Clin Infect Dis 64(7):894–901. https://doi.org/10.1093/cid/ciw876 CrossRefPubMedGoogle Scholar
- 9.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. https://doi.org/10.1016/j.ijid.2015.06.023 CrossRefPubMedGoogle Scholar
- 11.Liu YM, Li BB, Zhang YY, Zhang W, Shen H, Li H, Cao B (2014) Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China. Antimicrob Agents Chemother 58(9):5379–5385. https://doi.org/10.1128/aac.02523-14 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Catalan-Najera JC, Garza-Ramos U, Barrios-Camacho H (2017) Hypervirulence and hypermucoviscosity: two different but complementary Klebsiella spp. phenotypes? Virulence 8(7):1111–1123. https://doi.org/10.1080/21505594.2017.1317412
- 13.Lee HC, Chuang YC, Yu WL, Lee NY, Chang CM, Ko NY, Wang LR, Ko WC (2006) Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with community-acquired bacteraemia. J Intern Med 259(6):606–614. https://doi.org/10.1111/j.1365-2796.2006.01641.x CrossRefPubMedGoogle Scholar
- 18.Zhang Y, Zhao C, Wang Q, Wang X, Chen H, Li H, Zhang F, Li S, Wang R, Wang H (2016) High prevalence of Hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob Agents Chemother 60(10):6115–6120. https://doi.org/10.1128/aac.01127-16 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Compain F, Babosan A, Brisse S, Genel N, Audo J, Ailloud F, Kassis-Chikhani N, Arlet G, Decre D (2014) Multiplex PCR for detection of seven virulence factors and K1/K2 capsular serotypes of Klebsiella pneumoniae. J Clin Microbiol 52(12):4377–4380. https://doi.org/10.1128/jcm.02316-14 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Poirel L, Walsh TR, Cuvillier V, Nordmann P (2011) Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 70(1):119–123. https://doi.org/10.1016/j.diagmicrobio.2010.12.002 CrossRefPubMedGoogle Scholar
- 22.Russo TA, Olson R, MacDonald U, Beanan J, Davidson BA (2015) Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun 83(8):3325–3333. https://doi.org/10.1128/iai.00430-15 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Yu WL, Lee MF, Chen CC, Tang HJ, Ho CH, Chuang YC (2017) Impacts of hypervirulence determinants on clinical features and outcomes of bacteremia caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Microb Drug Resist 23(3):376–383. https://doi.org/10.1089/mdr.2016.0018 CrossRefPubMedGoogle Scholar
- 27.Cubero M, Grau I, Tubau F, Pallares R, Dominguez MA, Linares J, Ardanuy C (2016) Hypervirulent Klebsiella pneumoniae clones causing bacteraemia in adults in a teaching hospital in Barcelona, Spain (2007-2013). Clin Microbiol Infect 22(2):154–160. https://doi.org/10.1016/j.cmi.2015.09.025 CrossRefPubMedGoogle Scholar
- 28.Guo Y, Wang S, Zhan L, Jin Y, Duan J, Hao Z, Lv J, Qi X, Chen L, Kreiswirth BN, Wang L, Yu F (2017) Microbiological and clinical characteristics of hypermucoviscous Klebsiella pneumoniae isolates associated with invasive infections in China. Front Cell Infect Microbiol 7:24. https://doi.org/10.3389/fcimb.2017.00024 PubMedPubMedCentralGoogle Scholar
- 29.Pomakova DK, Hsiao CB, Beanan JM, Olson R, MacDonald U, Keynan Y, Russo TA (2012) Clinical and phenotypic differences between classic and hypervirulent Klebsiella pneumonia: an emerging and under-recognized pathogenic variant. Eur J Clin Microbiol Infect Dis 31(6):981–989. https://doi.org/10.1007/s10096-011-1396-6 CrossRefPubMedGoogle Scholar
- 30.Togawa A, Toh H, Onozawa K, Yoshimura M, Tokushige C, Shimono N, Takata T, Tamura K (2015) Influence of the bacterial phenotypes on the clinical manifestations in Klebsiella pneumoniae bacteremia patients: a retrospective cohort study. J Infect Chemother 21(7):531–537. https://doi.org/10.1016/j.jiac.2015.04.004 CrossRefPubMedGoogle Scholar
- 31.Gu D, Dong N, Zheng Z, Lin D, Huang M, Wang L, Chan EW, Shu L, Yu J, Zhang R, Chen S (2017) A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. https://doi.org/10.1016/s1473-3099(17)30489-9
- 32.Yu WL, Ko WC, Cheng KC, Lee CC, Lai CC, Chuang YC (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):1–6. https://doi.org/10.1016/j.diagmicrobio.2008.04.007 CrossRefPubMedGoogle Scholar
- 35.Zhang Y, Zeng J, Liu W, Zhao F, Hu Z, Zhao C, Wang Q, Wang X, Chen H, Li H, Zhang F, Li S, Cao B, Wang H (2015) Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate from clinical infections in China. J Inf Secur 71(5):553–560. https://doi.org/10.1016/j.jinf.2015.07.010 Google Scholar
- 36.Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, Losito AR, Bartoletti M, Del Bono V, Corcione S, Maiuro G, Tedeschi S, Celani L, Cardellino CS, Spanu T, Marchese A, Ambretti S, Cauda R, Viscoli C, Viale P (2015) Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 70(7):2133–2143. https://doi.org/10.1093/jac/dkv086 CrossRefPubMedGoogle Scholar
- 38.Girometti N, Lewis RE, Giannella M, Ambretti S, Bartoletti M, Tedeschi S, Tumietto F, Cristini F, Trapani F, Gaibani P, Viale P (2014) Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy. Medicine (Baltimore) 93(17):298–309. https://doi.org/10.1097/md.0000000000000111 CrossRefGoogle Scholar
- 39.Gomez-Simmonds A, Greenman M, Sullivan SB, Tanner JP, Sowash MG, Whittier S, Uhlemann AC (2015) Population structure of Klebsiella pneumoniae causing bloodstream infections at a New York city tertiary care hospital: diversification of multidrug-resistant isolates. J Clin Microbiol 53(7):2060–2067. https://doi.org/10.1128/jcm.03455-14 CrossRefPubMedPubMedCentralGoogle Scholar