ESBL Bacteria Resistance Profile
ESBL-producing bacteria are resistant to all penicillins, all cephalosporins (including third- and fourth-generation agents), aztreonam, and extended-spectrum penicillins, but remain susceptible to carbapenems. 1, 2
Core Resistance Pattern
ESBL enzymes hydrolyze the following antibiotic classes:
- All penicillins (including extended-spectrum penicillins like piperacillin) 3, 4
- All cephalosporins (first through fourth generation, including ceftriaxone, cefotaxime, ceftazidime, and cefepime) 1, 3, 5
- Aztreonam (the monobactam) 3, 4, 5
- Oxyimino-beta-lactams 1, 6
Co-Resistance Patterns
ESBL-producing organisms frequently carry additional resistance mechanisms on the same plasmid, creating multidrug-resistant phenotypes:
- Aminoglycosides (gentamicin, tobramycin) - frequently co-transferred 1, 3
- Trimethoprim-sulfamethoxazole - commonly co-resistant 1, 3, 4
- Fluoroquinolones (ciprofloxacin, levofloxacin) - increasingly associated 1, 4
- Tetracyclines - often co-resistant 1
This co-resistance pattern is critical because it eliminates most oral and many parenteral treatment options, leaving carbapenems as the primary therapeutic choice. 4
Antibiotics That Remain Effective
Carbapenems are the drugs of choice for serious ESBL infections and maintain consistent activity:
- Imipenem, meropenem, ertapenem - remain fully active against ESBL producers 1, 2, 3, 4
- Newer beta-lactam/beta-lactamase inhibitor combinations (ceftazidime-avibactam) - have activity against ESBLs 2
For uncomplicated infections (particularly urinary tract infections):
- Fosfomycin - may retain activity 2
- Nitrofurantoin - may retain activity 2
- Aminoglycosides - if susceptibility confirmed 2
Critical Clinical Pitfall
All confirmed ESBL producers must be reported as resistant to all penicillins, cephalosporins, and aztreonam regardless of in vitro susceptibility results. 5 This is because automated susceptibility testing may show false susceptibility, particularly with cefepime, where 24-95% of ESBL-producing organisms may appear susceptible but still fail clinically. 5
The newer CLSI interpretive criteria for cephalosporins may fail to identify many ESBL-producing organisms, making clinical suspicion and epidemiological context essential for appropriate therapy selection. 7
Mechanism-Specific Considerations
When ESBL producers also express AmpC beta-lactamases (common co-occurrence), they gain additional resistance to:
- Cephamycins (cefoxitin, cefotetan) 1, 3
- Beta-lactam/beta-lactamase inhibitor combinations may have reduced activity 3
However, carbapenems remain effective even against organisms co-producing ESBLs and AmpC enzymes. 1, 3