HABP/VABP is increasingly caused by carbapenem-resistant Gram-negative pathogens1

Carbapenem-resistant non-fermenters are frequent causative pathogens of nosocomial pneumonia1

  • In a study, as high as 28% of respiratory infections were carbapenem-non-susceptible, much higher than other sites of infection (3-10%)1*
    • In this study, 95% of carbapenem-non-susceptible respiratory infections were due to non-fermenters

Breakdown of carbapenem-non-susceptible respiratory infections1


Pie graph Enterobacteriaceae 89%, P aeruginosa 10%, A baumannii 0.5%, S maltophilia 0.4%
From a study identifying laboratory-confirmed infections in the Premier Healthcare Database between 2010 and 2015.
*Carbapenem resistance is defined as resistant or intermediate to meropenem, imipenem, or ertapenem.

Carbapenem resistance can be caused by a mix of 3 major mechanisms2,3

The 3 major mechanisms of carbapenem resistance include β-lactamase hydrolysis, efflux pump up-regulation, and porin channel changes
1

inactivates drug

  • In A baumannii, primary mechanism is OXA carbapenemase production (such as OXA-23) and all isolates contain chromosomally encoded OXA-514,5
  • Overexpression of AmpC has been reported in 47-66% of P aeruginosa isolates6,7
  • In one study with Enterobacteriaceae, 48% of carbapenem-resistant isolates contained KPC8
2

expels 𝛃-lactamase

  • P aeruginosa harbors the most efflux pumps of all Gram-negative organisms4
  • In one study with A baumannii, 80% of isolates had up-regulation of efflux pump4
3

limit drug access

  • In P aeruginosa, the most common mechanism is loss of OprD porin9
  • In Enterobacteriaceae, concomitant loss of porin channel and expression of ESBLs or AmpC often lead to carbapenem resistance4

Carbapenem-resistant mechanisms often coexist in hard-to-treat pathogens7,10-12