Bacterial enzymes that inactivate ß-lactam antibiotics by hydrolysis and make them ineffective agents.
As many as 450 different types have been isolated indicating they can inactivate a variety of antibiotics.
One group, the extended-spectrum ß-lactamases (ESBLs) are an increasingly significant cause of treatment failure.
Extended-spectrum ß-lactamases (ESBLs) have the ability to hydrolyze newer types of ß-lactam antibiotics.
β-Lactamases are bacterial enzymes that hydrolyze the β-lactam ring of penicillins, cephalosporins, monobactams, and—depending on the enzyme—carbapenems, thereby preventing binding to penicillin-binding proteins and inhibiting cell-wall synthesis.
Main Ambler classes
Serine β-lactamase TEM, SHV, CTX-M, KPC Penicillinases, extended-spectrum β-lactamases (ESBLs), and some carbapenemases
Zinc-dependent metallo-β-lactamase (MBL) NDM, VIM, IMP
Hydrolyzes most β-lactams, including carbapenems; monobactams are spared intrinsically
Serine cephalosporinase AmpC, CMY Resistance to many cephalosporins and cephamycins; usually not inhibited by clavulanate.
Serine oxacillinase OXA-48-like, OXA-23 Variable activity; some enzymes hydrolyze carbapenems
Clinically important phenotypes
ESBLs, especially CTX-M enzymes, hydrolyze penicillins, extended-spectrum cephalosporins, and aztreonam.
ESBL‘s are produced by several gram-negative pathogens, mostly E. coli and K pneumoniae, together, accounting for more than 90% of ESBL producing isolates.
ESBLs hydrolyze, most beta lactam antibiotics – excluding carbenems and are generally carried on plasmids that also harbor determininants of resistance to other antibiotic families, such as fluoroquinolones, trimethoprim-sulfamethoxazole,tetracyclines, and aminoglycosides further limiting therapeutic options.
In the US ESBL production is identified in approximately 20% of E. coli UTIs frequently leading to hospitalization,owning to limited oral treatment options.
The percentage of ESPN producing pathogens is notably higher in many of the countries.
AmpC may be inducible or plasmid-mediated and can emerge during exposure to certain β-lactams through derepression or increased expression.
Carbapenemases include KPC (class A), NDM/VIM/IMP (class B), and OXA-48-like enzymes (class D); they are particularly concerning because they compromise carbapenems.
β-Lactamase inhibitors such as clavulanate, tazobactam, avibactam, and vaborbactam have different spectra; none reliably inhibits every class, and avibactam does not significantly inhibit metallo-β-lactamases.
β-lactamase interpretation requires identifying the enzyme phenotype or genotype—particularly ESBL, AmpC, or carbapenemase—because the resistance spectrum and activity of β-lactam/β-lactamase-inhibitor combinations differ substantially.
E. Coli and Klebsiella organisms can produce extended spectrum ß-lactamases and are the major ESBLs worldwide.
Most ESBLs divided into 4 groups: TEM, SHV, OXA, and CTX-M types.
In 2011 CDC ESBL producing bacteria accounted for at least 26,000 infections and 1700 deaths annually.
ESBL increasingly common infections in the community and healthcare settings.
Carbpenems have been regarded as the treatment of choice for infections caused by ESBL producers