Updated overview of approaches to CRE 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

 * Falcone CID 2020, https://doi.org/10.1093/cid/ciaa586

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