Question
Extended spectrum beta lactamases
Answer
Extended-Spectrum Beta-Lactamases (ESBLs) are plasmid-encoded bacterial enzymes, mostly produced by Enterobacteriaceae (notably Escherichia coli and Klebsiella pneumoniae), that confer resistance to a broad range of beta-lactam antibiotics — including penicillins, and, distinctively, the extended-spectrum (third-generation) cephalosporins (cefotaxime, ceftazidime, ceftriaxone) and monobactams (aztreonam) — by hydrolysing the beta-lactam ring that is essential for the drugs’ antibacterial activity.
Mechanism: ESBLs are typically derivatives of older, narrower-spectrum beta-lactamases (e.g., TEM, SHV types) that have undergone point mutations expanding their substrate range to include the newer, extended-spectrum cephalosporins that were originally designed to be stable against the parent enzymes; ESBL genes are usually carried on transferable plasmids, which often also carry resistance genes to other antibiotic classes (aminoglycosides, fluoroquinolones, co-trimoxazole), producing multidrug-resistant strains.
Key features:
- ESBLs are typically inhibited by clavulanic acid (a beta-lactamase inhibitor) — this property is exploited in laboratory confirmatory testing (e.g., the double-disc synergy test, or combination disc test comparing zone sizes of a cephalosporin alone versus combined with clavulanic acid).
- Not effective against carbapenems (imipenem, meropenem) — carbapenems remain the treatment of choice for serious ESBL-producing organism infections, though carbapenem resistance (via separate carbapenemase enzymes) is an increasing concern.
Clinical significance: ESBL-producing organisms are an important cause of hospital-acquired and increasingly community-acquired infections (UTI, bloodstream infection, intra-abdominal infection), associated with treatment failure if standard cephalosporins are used empirically, higher morbidity/mortality, and the need for carbapenem-based or other alternative therapy; a major driver of concern in global antimicrobial resistance surveillance and infection-control programmes (screening, contact precautions, antibiotic stewardship).