Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

Abstract

Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

The threat of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP)

“…Several carbapenemases, such as K. pneumoniae Carbapenemases (KPC), carbapenemases of the oxacillinase-48 (OXA-48), and New Delhi metallo-β-lactamase (NDM) carbapenemases type, have been reported worldwide in K. pneumoniae [3][4][5]. Besides carbapenem resistance, another big problem of K. pneumoniae infection is the emergence of hypervirulent K. pneumoniae (HvKP) with hypervirulence [6][7][8]. This pathogen with the hypermucoviscous phenotype caused highly invasive infections, such as liver abscesses, in both healthy and immunocompromised individuals [7][8][9].…”

“…This pathogen with the hypermucoviscous phenotype caused highly invasive infections, such as liver abscesses, in both healthy and immunocompromised individuals [7][8][9]. Unlike the classic K. pneumoniae (cKP), approximately half of all HvKP infections occur in young, healthy individuals [6,9]. Many reports have determined hypervirulence-associated factors, including a K1/K2 capsular serotype, ST23 sequence type, a pLVPK virulence plasmid, a KPHP1208 pathogenicity island, and several virulence factors, such as RmpA and aerobactin [6].…”

“…Antibiotic resistance of cKP is significantly high worldwide [3], but HvKP is rarely resistant to antibiotics, except for an intrinsic resistance to ampicillin [6,10]. However, recent many reports have shown the emergence of antibiotic-resistant HvKP strains [6].…”

“…However, recent many reports have shown the emergence of antibiotic-resistant HvKP strains [6]. Especially, the emergence of Carbapenem-Resistant HvKP (CR-HvKP) was reported in China, where both carbapenem-resistant cKP (CRKP) and carbapenemsusceptible HvKP strains are prevalent [6,11].…”

“…However, recent many reports have shown the emergence of antibiotic-resistant HvKP strains [6]. Especially, the emergence of Carbapenem-Resistant HvKP (CR-HvKP) was reported in China, where both carbapenem-resistant cKP (CRKP) and carbapenemsusceptible HvKP strains are prevalent [6,11]. A recent study performed by Danxia et al showed the emergence of CRHvKP ST11 strains caused by the transfer of a 170 kb pLVPKlike virulence plasmid into bla KPC-2 -harboring ST11 CRKP stains [12].…”