What is Extended-Spectrum Beta-Lactamase (ESBL)?
ESBL refers to a group of plasmid-mediated enzymes produced by certain gram-negative bacteria that hydrolyze (break down) extended-spectrum cephalosporins, aztreonam, and penicillins, but remain inhibited by clavulanic acid and susceptible to carbapenems. 1
Mechanism and Enzyme Types
- ESBLs are enzymes that confer resistance by hydrolyzing the beta-lactam ring of antibiotics, rendering them ineffective 2, 3
- The most common ESBL types derive from TEM, SHV, and CTX-M enzyme families, with additional groups including KPC, AmpC, and certain OXA variants 1, 4
- These enzymes are typically encoded on plasmids, which allows for easy horizontal transfer between bacteria and often carry co-resistance genes for other antibiotic classes 2, 3
Common Organisms
- Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli are the most common ESBL-producing organisms 1
- Other Enterobacteriaceae including Proteus mirabilis, Enterobacter species, and Citrobacter species can also produce ESBLs 1
Resistance Profile
ESBL-producing bacteria are resistant to all penicillins, all cephalosporins (including third-generation cephalosporins like ceftriaxone, cefotaxime, ceftazidime, and fourth-generation cefepime), and aztreonam, but remain susceptible to carbapenems. 1
- Co-resistance to aminoglycosides (gentamicin, tobramycin), trimethoprim-sulfamethoxazole, and fluoroquinolones is frequently observed, severely limiting treatment options 1
- When ESBL producers also express AmpC beta-lactamases, they gain additional resistance to cephamycins, but carbapenems remain effective 1
Laboratory Detection
- ESBL-producing organisms are identified through antimicrobial susceptibility testing showing specific resistance patterns to beta-lactam antibiotics 5
- The Clinical and Laboratory Standards Institute (CLSI) states that routine ESBL testing is no longer necessary before reporting results when using newer interpretive criteria for cephalosporins 5
- Common to all ESBL detection methods is the principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid 2, 3
- MIC (Minimum Inhibitory Concentration) determination is another laboratory method used for ESBL detection 5
Important Caveat
- The new ceftazidime and cefepime susceptible breakpoints fail to identify many ESBL-producing E. coli, K. pneumoniae, and K. oxytoca, which can lead to inappropriate antibiotic selection 5
Clinical Significance
- Identification of ESBL-producing organisms is critical for appropriate antibiotic selection, as these infections are associated with higher mortality, complications, and prolonged hospitalization if not properly treated 6
- Carbapenems (imipenem, meropenem, ertapenem) are the treatment of choice for serious infections caused by ESBL-producing organisms 1, 5
- For uncomplicated infections, alternative treatments include fosfomycin, nitrofurantoin, and aminoglycosides, depending on susceptibility and infection type 1
- Newer agents such as ceftazidime-avibactam have activity against ESBL-producing organisms and may be valuable for treating infections to preserve carbapenems 1, 7