MICROBIOLOGY

• K. pneumoniae, K. oxytoca and K. granulomatis are Gram-negative, lactose-fermenting, aerobic bacilli [Fig 1] of the Enterobacterales order, Enterobacteriaceae family.
  • K. ozaenae and K. rhinoscleromatis are non-fermenting subspecies.[18]
  • Isolates are cultured on non-selective media for sterile specimens or MacConkey agar for contaminated specimens.
• Klebsiella species form highly mucoid colonies and produce a capsule polysaccharide matrix [Fig 2], a virulence factor that inhibits phagocytosis.
  • K. pneumoniae can survive as free-living and host-associated. These bacteria are present in mammalian intestinal and respiratory tracts and cause opportunistic infections in individuals with weakened immune systems exposed to healthcare environments.[16][10]
  • These bacteria contaminate sinks and cause nosocomial outbreaks, esp. K. pneumoniae and K. oxytoca.[19][13]
  • The emergence of hypervirulent strains has increased the risk of infection in immunocompetent hosts and therefore increased the number of people susceptible to infection.[17]
• Molecular classification of β-lactamase antimicrobial resistance based on amino acid sequence divides β-lactamases into Ambler Class A, C, and D serine β-lactamases and Class B metallo-β-lactamases. Classification of β-lactamases based on functional groups recognizes biochemical substrate and inhibition profiles to define β-lactamases according to enzymatic properties. Current nomenclature combines functional groups with molecular classes.[22]
• Beta-lactamases are constitutive, usually produced at low levels, and confer resistance against ampicillin, amoxicillin and first- and second-generation cephalosporins.
  • Few Klebsiellae lack these β-lactamases.
• Extended-spectrum β-lactamases (ESBLs) may be plasmid-mediated or chromosomal, confer multidrug resistance (TEM or SHV types), and are detected by in vitro resistance to ceftazidime and aztreonam.[22][12]
  
  • CTX-M type ESBLs are the most prevalent ESBL types worldwide and are commonly associated with ST131 E. coli.[23]
  • Non-susceptibility to ceftriaxone is often used as a proxy for ESBL production.[6] Yet organisms may be resistant to ceftriaxone for reasons other than ESBL production.[2]
• Carbapenemases
  
  • Klebsiella pneumoniae carbapenemase, KPC (Ambler Class A), confers broad resistance and is associated with high mortality rates.[21]
    • Many isolates in the U.S. are sequence-type ST258, a biologically fit lineage that can cause outbreaks.[15]
    • The phenotype includes strong potentiation of meropenem by vaborbactam.[15]
  • Metallo-β-lactamase (Ambler Class B) types include IMP (imipenemase), VIM (Verona integron-encoded MBL), and NDM-1 (New Delhi metallo-beta-lactamase).
    • Zinc ions are required for activity.
    • IMP and VIM are not resistant to aztreonam.
    • NDM-1 presence is strongly suggested by combined resistance to meropenem, ceftazidime, cefepime and evident susceptibility to aztreonam.
  • OXA-type carbapenemases (Ambler Class D): include OXA-48, weakly hydrolyze carbapenems, broad-spectrum cephalosporins, and aztreonam; express resistance or decreased susceptibility to carbapenems.
    • Often associated with Acinetobacter baumannii.