Extended-spectrum β‑lactamases (ESBLs) are enzymes produced by certain Gram‑negative bacteria that can break down and inactivate a broad range of β‑lactam antibiotics, including third‑generation cephalosporins and monobactams, but are inhibited by β‑lactamase inhibitors.
Explanation
ESBLs are plasmid‑encoded enzymes that hydrolyse the β‑lactam ring of many antibiotics. They evolved from narrow‑spectrum β‑lactamases through mutations that expanded their substrate range. Bacteria producing ESBLs are usually members of the Enterobacterales, particularly Escherichia coli and Klebsiella pneumoniae. The genes encoding ESBLs are often located on conjugative plasmids that also carry resistance determinants to other antibiotic classes, leading to multidrug resistance. Clinically, infections caused by ESBL‑producing organisms include urinary tract infections, intra‑abdominal infections, pneumonia and sepsis. Standard susceptibility testing may fail to detect ESBL production, so confirmatory tests using clavulanic acid inhibition or molecular assays are used. Because ESBLs confer resistance to penicillins, aztreonam and extended‑spectrum cephalosporins, treatment options are limited. Carbapenems are typically considered the drugs of choice for severe infections, although β‑lactam/β‑lactamase inhibitor combinations and novel cephalosporins may be effective. Preventing the spread of ESBL‑producing bacteria requires infection control measures, antimicrobial stewardship and surveillance in both healthcare and community settings.
Clinical Context and Resistance Implications
ESBL‑producing E. coli are a leading cause of community‑acquired urinary tract infections, often associated with travel or previous antibiotic use. Klebsiella pneumoniae strains carrying ESBL genes cause outbreaks in hospitals, particularly in intensive care units, leading to ventilator‑associated pneumonia and bloodstream infections. Other members of Enterobacterales, such as Proteus mirabilis and Enterobacter cloacae complex, can also harbour ESBLs. The emergence of CTX‑M‑type ESBLs has shifted the epidemiology from hospital to community settings. Because ESBL genes are plasmid‑borne, they can spread rapidly between bacteria of different species. Surveillance and prudent use of antibiotics are critical to slowing this spread.
ESBLs exemplify how bacterial enzymes can undermine antibiotic efficacy and highlight the importance of coordinated infection control and thoughtful antibiotic selection when treating Gram‑negative infections.
Related Terms: Beta-lactamase, Carbapenemase, Antibiotic resistance, Enterobacterales, Cephalosporin