Guest posting from Professors Josh Davis (Hunter New England Health) and Patrick Harris (UQ).
|AMBLER CLASS||Class A||Class B||Class D|
|Key characteristic||Serine group enzyme||Metallo-betalactamase||OXA-type|
|Key example(s)||KPC, GES||IMP, NDM, VIM||OXA-48. (OXA-181, OXA-232 emerging)|
|Susceptiblity features||R to all b-lactams||R to all b-lactams except Aztreonam
May harbour other ESBLS, AmpC enzymes or KPCs encoding Aztreonam R, and these are inhibited by Avibactam
|Often, but not always R to all b-lactams
OXA does not confer cephalosporin R, but co-existing ESBL often present
|Inhibited by avibactam||Yes||No||Yes|
|Inhibited by vaborbactam||Yes||No||No|
|Inhibited by clavulanate and tazobactam||Variable||No||No|
|Main Rx options||Ceftaz-Avi||Ceftaz-Avi plus Aztreonam
|Other Rx options||Add Mero if Intermediate MIC
|Colistin plus meropenem (Mero MIC<=8)
Colistin plus tigecycline (Mero MIC>8)
|Often low level carbapenem-R, so mero MICs may allow use (usually in combination where possible)|
|Notes||CTX-M, TEM, SHV are class A b-lactmases but are NOT carbepenemases
Mero+colistin failed in RCT
|Ceftaz-Avi plus Aztreonam has emerging supportive observational data*.
Even in Aztreonam R isolates, the Avi likely restores Aztreonam S. The Ceftaz is not needed, so when Atztreonam/Avi becomes available it will replace Ceftaz/Avi+Aztreonam.
|Ceftaz-Avi is 2.5g q8h, extended infusion|
- Class C b-lactamases are cephalosporinases, as in ESCPPM group (may give rise to CRE if combined AmpC hyper-expression and porin changes);
- Cefiderocol likely effective against most CREs but possible increased mortality in Acinetobacter infections (GAMECHANGER trial will report on this in 2023/4).
- For more detail on MRGN Rx and consensus guidelines see https://www.idsociety.org/practice-guideline/amr-guidance/#Carbapenem-ResistantEnterobacterales
* Falcone CID 2020, https://doi.org/10.1093/cid/ciaa586