On what basis is a bacterium deemed as Extended-Spectrum Beta-Lactamase (ESBL) in sensitivity testing?

ESBL Identification Based on Cephalosporin Resistance

A bacterium is deemed ESBL-producing based on resistance to third-generation cephalosporins (ceftazidime, cefotaxime, ceftriaxone) and aztreonam, with confirmatory testing showing enhanced susceptibility when these antibiotics are combined with clavulanic acid. 1, 2

Core Screening Antibiotics

The primary drugs used to identify ESBL-producing organisms are:

• Third-generation cephalosporins: Specifically ceftazidime, cefotaxime, and ceftriaxone 3, 2, 4
• Aztreonam (a monobactam antibiotic) 3, 2
• Cefepime (fourth-generation cephalosporin) is also hydrolyzed by ESBLs 3

Confirmatory Testing Principle

The hallmark of ESBL detection is demonstrating that clavulanic acid (a beta-lactamase inhibitor) restores susceptibility to these cephalosporins. 2 This distinguishes ESBLs from other resistance mechanisms like AmpC beta-lactamases, which are not inhibited by clavulanic acid.

Important Testing Caveats

Modern CLSI Guidelines Have Changed the Approach

• As of 2010, CLSI guidelines state that routine ESBL testing is no longer necessary before reporting results when using newer interpretive criteria for cephalosporins. 5, 6
• However, ESBL testing remains valuable for epidemiological and infection control purposes 5, 6

Critical Limitation of New Breakpoints

• The new ceftazidime (≤4 μg/mL) and cefepime (≤8 μg/mL) susceptible breakpoints fail to identify many ESBL-producing E. coli, K. pneumoniae, and K. oxytoca. 5, 6
• This means some ESBL producers may appear "susceptible" on automated testing but still carry the resistance mechanism 5

Resistance Pattern That Defines ESBL

ESBL-producing bacteria demonstrate:

• Resistance to all penicillins, all cephalosporins (including third-generation), and aztreonam 1
• Preserved susceptibility to carbapenems (imipenem, meropenem, ertapenem) 1, 3
• Inhibition by clavulanic acid - this is the key confirmatory feature 2

Common Co-Resistances

ESBL producers frequently carry additional resistance genes affecting:

• Aminoglycosides (gentamicin, tobramycin) 1
• Fluoroquinolones 1
• Trimethoprim-sulfamethoxazole 1

Clinical Pitfall to Avoid

Never rely on apparent "susceptibility" to third-generation cephalosporins in treating serious ESBL infections, even if the lab reports susceptibility. 2, 7 Treatment with cephalosporins has been associated with high failure rates despite in vitro susceptibility 2. Carbapenems remain the treatment of choice for serious ESBL infections 1, 3.