Carbapenemases

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Background

  • Enzymes that hydrolyze carbapenems
  • Includes members of most Ambler classes
    • Class A: KPC
    • Class B: NDM, IMI, VIM
    • Class C: AmpCs
    • Class D: 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

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

Management