ESBL Definition Based on Antibiotic Resistance Pattern
E. coli is considered ESBL-producing when it demonstrates resistance to third-generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) and aztreonam, while remaining susceptible to carbapenems and showing inhibition by clavulanic acid. 1
Core Resistance Pattern Required for ESBL Classification
ESBL-producing E. coli must demonstrate resistance to the following antibiotics:
- All penicillins (including extended-spectrum penicillins) 1
- All cephalosporins, specifically:
- Aztreonam (oxyimino-monobactam) 1, 2
The defining characteristic is that ESBL enzymes hydrolyze these extended-spectrum cephalosporins through enzymatic activity 2.
Key Distinguishing Features
Preserved susceptibility to carbapenems (imipenem, meropenem, ertapenem) is the hallmark that distinguishes ESBL producers from carbapenemase-producing organisms 1. This carbapenem susceptibility remains the critical differentiating factor, as ESBL enzymes do not hydrolyze carbapenem antibiotics 1.
Inhibition by clavulanic acid is another defining characteristic - when clavulanic acid is added to cephalosporins in laboratory testing, it restores activity against ESBL producers, which forms the basis of confirmatory testing 1.
Laboratory Confirmation
The double-disk synergy test demonstrates a characteristic "champagne cork" shaped zone of inhibition when disks containing cephalosporins are placed near a disk containing amoxicillin-clavulanate 3. This synergy pattern confirms ESBL production, as the clavulanic acid inhibits the ESBL enzyme and restores cephalosporin activity 4.
Common Co-Resistance Patterns
While not required for ESBL classification, these organisms frequently carry additional resistance mechanisms:
- Fluoroquinolones (ciprofloxacin, levofloxacin) - resistance rates of 55-100% 1, 3, 5
- Aminoglycosides (gentamicin, tobramycin) - frequently co-resistant 1
- Trimethoprim-sulfamethoxazole - commonly resistant 1, 5
These co-resistances occur because ESBL genes are often located on plasmids that carry multiple resistance determinants, but they are not part of the ESBL definition itself 1.
Clinical Implications
Research demonstrates that all ESBL-producing E. coli isolates show 100% resistance to ceftazidime and cefotaxime, with high resistance to cefepime (32%), making these cephalosporins ineffective for treatment 5. In contrast, carbapenems maintain 100% susceptibility against ESBL producers, which is why they remain the treatment of choice for serious infections 5.