Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and...

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Treatment of infections caused by OXA-48/CTX-M-coproducing Enterobacterales involves ceftazidime/avibactam (CZA) or high-dose meropenem (MER).
• Bacterial density at infection sites varies, and the inoculum effect on these antimicrobial strategies is not well-understood.
• Investigating the impact of high bacterial inocula on CZA and MER susceptibility in these specific Enterobacterales is crucial.

Purpose of the Study:

• To determine if ceftazidime/avibactam (CZA) or meropenem (MER) susceptibilities are affected by high inocula of Enterobacterales co-expressing OXA-48-like and CTX-M enzymes.

Main Methods:

• Evaluated the inoculum effect on antimicrobial susceptibility using standard (0.5 McFarland), twofold increased (1 McFarland), and tenfold increased (5 McFarland) inocula.
• Tested 39 isolates of ceftazidime-resistant Enterobacterales co-expressing OXA-48/CTX-M variants.

Main Results:

• Ceftazidime/avibactam (CZA) susceptibility remained stable across all tested inocula.
• Meropenem (MER) susceptibility decreased with increasing inocula: 61.5% at standard, 48.7% at twofold, and 38.5% at tenfold increase.
• Thirty-nine isolates were analyzed, with common co-expressions including OXA-48 + CTX-M-15.

Conclusions:

• An in vitro inoculum effect was observed for meropenem (MER) but not for ceftazidime/avibactam (CZA) in OXA-48- and CTX-M-producing Enterobacterales.
• Ceftazidime/avibactam demonstrates reliable activity irrespective of bacterial load.
• Meropenem's efficacy may be compromised in high-bacterial-density infections caused by these resistant strains.