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Impact of the inoculum effect on cefepime activity against AmpC-hyperproducing Enterobacter spp.: insights into

Ángel Rodríguez-Villodres1,2,3, Carmen Soto-Gallego1,2, José Manuel Ortiz De La Rosa1,2,3

  • 1Clinical Unit of Infectious Diseases, Microbiology and Parasitology, University Hospital Virgen del Rocío, Seville, Spain.

The Journal of Antimicrobial Chemotherapy
|April 23, 2025
PubMed
Abstract

Insights

High bacterial loads significantly reduce cefepime effectiveness against AmpC-hyperproducing Enterobacter spp. by increasing resistance. This necessitates tailored antimicrobial strategies for better patient outcomes.

Area of Science:

  • Clinical microbiology
  • Infectious diseases
  • Antimicrobial resistance

Background:

  • Antimicrobial resistance in Enterobacter spp. is a major healthcare concern due to AmpC β-lactamase hyperproduction.
  • Cefepime efficacy can be compromised by high bacterial loads.

Purpose of the Study:

  • To evaluate the impact of bacterial inoculum size on cefepime activity against AmpC-hyperproducing Enterobacter spp. clinical isolates.

Main Methods:

  • Minimum inhibitory concentrations (MICs) were determined using broth microdilution at standard and high inocula.
  • Kaplan-Meier survival analysis, time-kill assays, and measurement of β-lactamase activity were performed.

Main Results:

  • High inoculum significantly increased cefepime MICs (MIC50: 8 mg/L, MIC90: 256 mg/L) and resistance rates (from 6.5% to 54.8%).
  • The inoculum effect was observed in 61.3% of isolates, linked to higher β-lactamase activity and cefepime hydrolysis.

Conclusions:

  • Bacterial inoculum size critically affects cefepime efficacy in AmpC-hyperproducing Enterobacter spp. infections.
  • Optimized antimicrobial strategies are crucial for high bacterial load infections to improve outcomes and combat resistance.

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