Antimicrobial Resistance Pattern, Pathogenicity and Molecular Properties of Hypervirulent Klebsiella pneumonia (hvKp) among Hospital-Acquired Infections in the Intensive Care Unit (ICU)

Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-β-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, <0.001, <0.001, 0.037 and <0.001, respectively). However, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections.

[1]  Chao Liu,et al.  Hypervirulent Klebsiella pneumoniae (hypermucoviscous and aerobactin positive) infection over 6 years in the elderly in China: antimicrobial resistance patterns, molecular epidemiology and risk factor , 2019, Annals of Clinical Microbiology and Antimicrobials.

[2]  B. Veeraraghavan,et al.  Extremely High Mortality Rates in Patients with Carbapenem-resistant, Hypermucoviscous Klebsiella pneumoniae Blood Stream Infections. , 2018, The Journal of the Association of Physicians of India.

[3]  G. El-Kannishy,et al.  Hypervirulent Klebsiella pneumoniae as a hospital-acquired pathogen in the intensive care unit in Mansoura, Egypt. , 2018, Germs.

[4]  R. Saito,et al.  Clinical and microbiological characteristics and occurrence of Klebsiella pneumoniae infection in Japan , 2018, International journal of general medicine.

[5]  K. Holt,et al.  Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination , 2017, bioRxiv.

[6]  U. Garza-Ramos,et al.  Hypervirulence and hypermucoviscosity: Two different but complementary Klebsiella spp. phenotypes? , 2017, Virulence.

[7]  Zhaohui Ni,et al.  The Determination and Correlation of Various Virulence Genes, ESBL, Serum Bactericidal Effect and Biofilm Formation of Clinical Isolated Classical Klebsiella pneumoniae and Hypervirulent Klebsiella pneumoniae from Respiratory Tract Infected Patients , 2017, Polish journal of microbiology.

[8]  Ruobing Wang,et al.  High Prevalence of Hypervirulent Klebsiella pneumoniae Infection in China: Geographic Distribution, Clinical Characteristics, and Antimicrobial Resistance , 2016, Antimicrobial Agents and Chemotherapy.

[9]  S. Abd-Elsalam Identification of Ascitic Fluid Bacterial Pathogens in Spontaneous Bacterial Peritonitis in Nile Delta and Its Impact on Clinical Outcome of these Patients , 2016 .

[10]  S. Abd-Elsalam,et al.  Detection of Hypervirulent Klebsiella pneumoniae in Tanta University Hospital, Egypt , 2016 .

[11]  B. Cao,et al.  Emergence of a hypervirulent carbapenem-resistant Klebsiella pneumoniae isolate from clinical infections in China. , 2015, The Journal of infection.

[12]  P. Andersen,et al.  Mapping the Evolution of Hypervirulent Klebsiella pneumoniae , 2015, mBio.

[13]  A. Togawa,et al.  Influence of the bacterial phenotypes on the clinical manifestations in Klebsiella pneumoniae bacteremia patients: A retrospective cohort study. , 2015, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[14]  T. Russo,et al.  Aerobactin, but Not Yersiniabactin, Salmochelin, or Enterobactin, Enables the Growth/Survival of Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae Ex Vivo and In Vivo , 2015, Infection and Immunity.

[15]  Hui Li,et al.  Clinical and Molecular Characteristics of Emerging Hypervirulent Klebsiella pneumoniae Bloodstream Infections in Mainland China , 2014, Antimicrobial Agents and Chemotherapy.

[16]  T. Russo,et al.  Aerobactin Mediates Virulence and Accounts for Increased Siderophore Production under Iron-Limiting Conditions by Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae , 2014, Infection and Immunity.

[17]  Sarah-Jane Bailey,et al.  Klebsiella pneumoniae liver abscess and endophthalmitis , 2013, BMJ Case Reports.

[18]  C. Murray,et al.  Biofilm formation by clinical isolates and the implications in chronic infections , 2013, BMC Infectious Diseases.

[19]  T. Russo,et al.  Hypervirulent (hypermucoviscous) Klebsiella pneumoniae , 2013, Virulence.

[20]  Chang-Phone Fung,et al.  Klebsiella pneumoniae liver abscess: a new invasive syndrome. , 2012, The Lancet. Infectious diseases.

[21]  H. Tai,et al.  Recent trend of necrotizing fasciitis in Taiwan: focus on monomicrobial Klebsiella pneumoniae necrotizing fasciitis. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  Cheng-Hsien Lu,et al.  Adult Klebsiella pneumoniae meningitis in Taiwan: an overview. , 2012, Acta neurologica Taiwanica.

[23]  Y. Lai,et al.  Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain , 2011, BMC Microbiology.

[24]  Kuender D Yang,et al.  Hypermucoviscosity associated with Klebsiella pneumoniae-mediated invasive syndrome: a prospective cross-sectional study in Taiwan. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[25]  R. Tournebize,et al.  Virulent Clones of Klebsiella pneumoniae: Identification and Evolutionary Scenario Based on Genomic and Phenotypic Characterization , 2009, PloS one.

[26]  Shih-Feng Tsai,et al.  Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess. , 2008, The Journal of infectious diseases.

[27]  Y. Keynan,et al.  Capsular Polysaccharide Synthesis Regions in Klebsiella pneumoniae Serotype K57 and a New Capsular Serotype , 2008, Journal of Clinical Microbiology.

[28]  P. Hsueh,et al.  Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[29]  R. Domiati-Saad,et al.  Invasive Klebsiella pneumoniae syndrome in North America. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  Te‐Li Chen,et al.  Capsular Serotype K1 or K2, Rather than magA and rmpA, Is a Major Virulence Determinant for Klebsiella pneumoniae Liver Abscess in Singapore and Taiwan , 2006, Journal of Clinical Microbiology.

[31]  F. Chang,et al.  magA is not a specific virulence gene for Klebsiella pneumoniae strains causing liver abscess but is part of the capsular polysaccharide gene cluster of K. pneumoniae serotype K1. , 2006, Journal of medical microbiology.

[32]  W. Ko,et al.  Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  Shan-Chwen Chang,et al.  Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. , 2006, The Journal of infectious diseases.

[34]  D. Sandvang,et al.  Increased Serum Resistance in Klebsiella pneumoniae Strains Producing Extended-Spectrum β-Lactamases , 2004, Antimicrobial Agents and Chemotherapy.

[35]  Chia-Tung Shun,et al.  A Novel Virulence Gene in Klebsiella pneumoniae Strains Causing Primary Liver Abscess and Septic Metastatic Complications , 2004, The Journal of experimental medicine.

[36]  A. Gupta Hospital-acquired infections in the neonatal intensive care unit--Klebsiella pneumoniae. , 2002, Seminars in perinatology.

[37]  Herman Goossens,et al.  Community-Acquired Klebsiella pneumoniae Bacteremia: Global Differences in Clinical Patterns , 2002, Emerging infectious diseases.

[38]  R. Podschun,et al.  Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors , 1998, Clinical Microbiology Reviews.

[39]  W. Hsu,et al.  Klebsiella meningitis in Taiwan: an overview , 1997, Epidemiology and Infection.

[40]  D. Gu,et al.  A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. , 2018, The Lancet. Infectious diseases.

[41]  E. Pérez-Rodríguez,et al.  Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. , 1989, Archives of internal medicine.