Updated overview of approaches to CRE/ CPE treatment

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 Cefiderocol	Ceftaz-Avi
Other Rx options	Add Mero if Intermediate MIC Mero/Vabor	Colistin plus meropenem (Mero MIC<=8) Colistin plus tigecycline (Mero MIC>8) IV fosfomycin	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

Tags: CPE

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