What is ESBL (Extended-Spectrum Beta-Lactamase)?

Extended-Spectrum Beta-Lactamase (ESBL) Definition

Extended-spectrum beta-lactamases (ESBLs) are enzymes produced by Gram-negative bacteria that hydrolyze extended-spectrum cephalosporins and aztreonam while being inhibited by clavulanic acid, conferring resistance to many commonly used antibiotics. 1

Key Characteristics of ESBLs

• ESBLs are primarily produced by Enterobacteriaceae, especially Klebsiella pneumoniae, K. oxytoca, Escherichia coli, and Proteus mirabilis 2, 1
• They derive from mutations in genes for TEM-1, TEM-2, or SHV-1 beta-lactamases that alter the amino acid configuration around the active site, extending the spectrum of beta-lactam antibiotics they can hydrolyze 1
• Non-TEM/SHV ESBLs have emerged, with CTX-M enzymes becoming increasingly prevalent, particularly in community-acquired infections 3
• ESBLs are frequently plasmid-encoded, allowing for horizontal transfer between bacterial species 1
• These plasmids often carry genes conferring resistance to multiple other antibiotic classes (aminoglycosides, fluoroquinolones, tetracyclines, trimethoprim/sulfamethoxazole), severely limiting treatment options 1, 3

Clinical Significance

• ESBL-producing organisms cause infections ranging from uncomplicated urinary tract infections to life-threatening sepsis 2, 4
• Infections with ESBL-producers are associated with higher morbidity, mortality, and healthcare costs 4
• ESBL-producing bacteria may appear susceptible to some extended-spectrum cephalosporins in laboratory tests, but treatment with these antibiotics often results in clinical failure 1
• Carbapenems are considered the treatment of choice for serious infections caused by ESBL-producing organisms 5, 1
• Alternative treatments for uncomplicated infections may include:
  • Fosfomycin for uncomplicated lower UTIs (>95% susceptibility) 5
  • Nitrofurantoin for E. coli UTIs (not effective against other Enterobacteriaceae or upper UTIs) 5
  • Aminoglycosides for non-severe UTIs if susceptibility is confirmed 5

Laboratory Detection

• Detection of ESBLs is based on the principle that their activity against extended-spectrum cephalosporins is enhanced by the presence of clavulanic acid 2, 1
• The Clinical and Laboratory Standards Institute provides guidelines for ESBL detection in K. pneumoniae, K. oxytoca, E. coli, and P. mirabilis 2
• Rapid molecular identification methods can significantly reduce time to appropriate therapy 6

Epidemiology and Risk Factors

• ESBL prevalence is increasing worldwide, both in healthcare and community settings 4, 3
• Risk factors for ESBL infections include:
  • Recent antibiotic exposure (particularly beta-lactams or fluoroquinolones) within 90 days 6
  • Known colonization with ESBL-producing Enterobacteriaceae 6
  • Healthcare-associated infections 6
  • Hospitalization, especially in intensive care units 7

Prevention and Control

• Infection control measures should focus on reducing patient-to-patient transmission via the environment, healthcare personnel, and medical equipment 3
• Judicious use of antibiotics is essential to prevent further selection and spread of ESBL-producing organisms 3
• Active surveillance in high-risk patients can help identify colonization and prevent dissemination 7

Treatment Challenges

• ESBL-producing bacteria often exhibit co-resistance to multiple antibiotic classes, severely limiting treatment options 2, 3
• Carbapenem-resistant isolates have emerged, further complicating treatment 7, 1
• The emergence of carbapenem-resistant Enterobacteriaceae represents a potential shift from multi-drug resistant (MDR) to extensively drug-resistant (XDR) or even pandrug-resistant (PDR) bacteria 7

ESBLs represent a significant public health threat due to their increasing prevalence and the limited treatment options available for infections caused by these organisms 4.