Carbapenemases

From IDWiki

Background

  • Enzymes that hydrolyze carbapenems
  • Includes members of all Ambler classes, and corresponds to Bush-Jacoby classes 2df, 2f, 3a, and 3b
    • Class A (2f): KPC, IMI
    • Class B (3a and 3b): NDM, IMP, VIM
    • Class C: AmpCs (occasionally weakly active against carbapenems)
    • Class D (2df): OXA-48

Identification

  • Screening is done by identifying isolates with decreased susceptibility to one or more carbapenems
  • A modified Hodge test can confirm the presence of a carbapenemase, but is no longer routinely recommended
  • Modified carbapenem inactivation method (mCIM)
    • Place meropenem disc in a suspension of the test isolate, and incubate at 35ºC for 4 hours
    • Remove disc, squeezing out excess fluid, and place on a lawn of susceptible Escherichia coli
    • Positive for carbapenemase if zone diameter is clear ≤15 mm (or pinpoint colonies up to 18 mm)
    • Negative if zone diameter is clear ≥19 mm
    • Indeterminate if clear diameter 16 to 18 mm, or pinpoint colonies ≥19 mm
  • EDTA-modified carbapenem inactivation method (eCIM)
    • Only done if mCIM is positive, to test for metallo-β-lactamases
    • As above for mCIM, but adds EDTA to the tube
    • Positive for metallo-β-lactamase if zone diameter increases ≥5 mm from mCIM
      • Ignore pinpoint colonies within any zones of inhibition in the eCIM
  • Double disc diffusion (using Rosco discs)
    • Class A: attenuated by boronic acid
    • Class B: attenuated by diploconic acid
    • Class C: attenuated by both cloxacillin and boronic acid
    • Class D: not attenuated by boronic acid, diploconic acid, or cloxacillin
      • Needs special discs, or PCR testing

Inhibitors

  • Avibactam: active against ESBLs, AmpCs, KPC, and OXA-48, but not MBLs and other OXAs
    • Only inhibitor with some activity against class D (OXAs)
  • Relebactam: active against ESBLs, AmpCs, and KPC, but not OXA-48, VIM, GES, or MBLs
  • Tazobactam: active against Pseudomonas, but limited activity against carbapenemases otherwise
  • Vaborbactam: active against KPC, but limited activity against MBLs and OXA-48, Pseudomonas, or Acinetobacter

Specific Carbapenemases

Management

References

  1. ^  Jeanette W. P. Teo, My-Van La, Prabha Krishnan, Brenda Ang, Roland Jureen, Raymond T. P. Lin. Enterobacter cloacae producing an uncommon class A carbapenemase, IMI-1, from Singapore. Journal of Medical Microbiology. 2013;62(7):1086-1088. doi:10.1099/jmm.0.053363-0.