Towards a phenotypic screening strategy for emerging β-lactamases in Gram-negative bacilli

Area of Science:

• Microbiology
• Clinical Diagnostics
• Antimicrobial Resistance

Background:

• Emerging beta-lactamases, including extended-spectrum beta-lactamases (ESBLs), AmpC, and carbapenemases, pose a significant threat in Gram-negative bacilli (GNB).
• Accurate and timely phenotypic detection of these enzymes is crucial for effective patient management and infection control.

Purpose of the Study:

• To review current literature and guidelines on the phenotypic detection of emerging beta-lactamases in GNB.
• To formulate evidence-based recommendations for best practices in screening for these resistance mechanisms.

Main Methods:

• Literature and guideline review on phenotypic detection of ESBLs, AmpC, and carbapenemases in GNB.
• Evaluation of various screening and confirmation assays, including chromogenic agar, combined double-disk synergy tests (CDDST), and disk diffusion tests (DDST).
• Assessment of specific antimicrobial agents (ceftazidime, ceftriaxone, cefotaxime, cefepime, cefoxitin, cefotetan, meropenem) and inhibitors (3-aminophenylboronic acid, cloxacillin, ethylene diamine tetra-acetic-acid).

Main Results:

• Chromogenic ESBL screening agar is suitable for ESBL-producing Enterobacteriaceae.
• Ceftazidime (CAZ) and ceftriaxone/cefotaxime (CTX) are key for ESBL detection.
• Adapted CDDSTs with inhibitors are recommended for AmpC confirmation in co-producing Enterobacteriaceae.
• Reduced cefoxitin/cefotetan susceptibility indicates AmpC production.
• Meropenem breakpoint (0.5 μg/mL) is suggested for carbapenemase screening.
• Boronic acid-based and EDTA-based assays are recommended for carbapenemase confirmation.

Conclusions:

• Phenotypic detection methods and indicator antimicrobial agents should be tailored to the specific bacterial genus and resistance mechanism.
• Standardized screening and confirmation strategies are essential for managing infections caused by multidrug-resistant GNB.