Defining Extended-Spectrum Beta-Lactamase (ESBL) Bacteria
ESBL-producing bacteria are defined by their ability to hydrolyze extended-spectrum cephalosporins (ceftazidime, ceftriaxone, cefotaxime) and aztreonam while remaining inhibited by clavulanic acid and susceptible to carbapenems. 1, 2
Core Resistance Pattern (Defining Criteria)
The fundamental characteristics that define ESBL bacteria include:
- Resistance to all penicillins, all cephalosporins (including third-generation), and aztreonam 1
- Preserved susceptibility to carbapenems (imipenem, meropenem, ertapenem) 1, 2
- Inhibition by clavulanic acid - this is a key distinguishing feature used in laboratory confirmation 1, 2
The resistance pattern specifically includes hydrolysis of:
- All extended-spectrum cephalosporins: ceftriaxone, cefotaxime, ceftazidime, and cefepime 1
- Monobactams: aztreonam 2, 3
- Extended-spectrum penicillins 1
Enzyme Classification
ESBL enzymes are classified as functional group 2be beta-lactamases and typically derive from:
- TEM-type enzymes (originally TEM-1, TEM-2) through point mutations 2, 4
- SHV-type enzymes (originally SHV-1) through mutations altering the active site 2, 4
- CTX-M-type enzymes - increasingly common non-TEM/SHV ESBLs 4
- Other plasmid-mediated enzymes including VEB and OXA derivatives 4
These are mutant enzymes that extend the substrate spectrum beyond their parent beta-lactamases through amino acid configuration changes around the active site 2.
Laboratory Detection Criteria
According to the Clinical and Laboratory Standards Institute (CLSI):
- Routine ESBL testing is no longer necessary before reporting results when using newer interpretive criteria for cephalosporins 1, 5
- ESBL testing remains valuable for epidemiological and infection control purposes 1, 5
- The general detection principle: activity of extended-spectrum cephalosporins is enhanced by the presence of clavulanic acid 2, 6
Important caveat: The new ceftazidime and cefepime susceptible breakpoints may fail to identify many ESBL-producing E. coli, K. pneumoniae, and K. oxytoca, so these breakpoints should be used with caution 1, 5.
Common ESBL-Producing Organisms
- Klebsiella pneumoniae and Klebsiella oxytoca - most commonly reported worldwide 1, 6
- Escherichia coli 1, 6
- Other Enterobacteriaceae: Proteus mirabilis, Enterobacter species, Citrobacter species 1, 6
Co-Resistance Patterns (Not Defining, But Frequently Present)
ESBL-producing organisms frequently carry additional resistance mechanisms on the same plasmids:
This co-resistance severely limits therapeutic options but is not part of the ESBL definition itself 2, 6.
What Does NOT Define ESBLs
- Cephamycin resistance - traditional TEM/SHV-derived ESBLs remain susceptible to cephamycins, though newer class C transferable cephalosporinases may confer this resistance 7
- Carbapenem resistance - by definition, ESBLs remain susceptible to carbapenems; carbapenem resistance indicates additional mechanisms 1, 2