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

Extended Spectrum Beta-Lactamase (ESBL) Infections

Extended Spectrum Beta-Lactamase (ESBL) infections are caused by bacteria that produce enzymes capable of hydrolyzing extended-spectrum cephalosporins and aztreonam while being inhibited by clavulanic acid, rendering many common antibiotics ineffective and posing significant treatment challenges.

What Are ESBLs?

• ESBLs are a group of plasmid-mediated, diverse, complex, and rapidly evolving enzymes produced by certain bacteria, primarily Enterobacteriaceae 1
• These enzymes hydrolyze third-generation cephalosporins and aztreonam but are inhibited by clavulanic acid 1
• ESBL enzymes derive primarily from older TEM and SHV β-lactamases, though CTX-M enzymes are now becoming the prevalent type 2
• AVYCAZ (ceftazidime-avibactam) demonstrates in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA) 3

Common ESBL-Producing Organisms

• Klebsiella pneumoniae and Klebsiella oxytoca (most common) 4, 5
• Escherichia coli 4, 5
• Other Enterobacteriaceae including Proteus mirabilis, Enterobacter species, and Citrobacter species 4
• ESBL production has been found in up to 80% of Klebsiella species in some settings 5

Clinical Significance

• ESBL-producing organisms cause infections ranging from uncomplicated urinary tract infections to life-threatening sepsis 1
• These infections are associated with higher mortality, complications, and prolonged hospitalization if not properly treated 6
• ESBL-producing bacteria often exhibit co-resistance to multiple other antibiotic classes, including fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole 2
• Carbapenems are generally considered the treatment of choice for serious infections caused by ESBL-producing organisms 1, 7

Risk Factors for ESBL Infections

• Recent exposure to antibiotics (particularly beta-lactams or fluoroquinolones) within 90 days 4, 7
• Known colonization with ESBL-producing Enterobacteriaceae 4, 7
• Healthcare-associated infections 4, 7
• Hospitalization, especially in intensive care units 7
• Complex urological abnormalities (particularly in pediatric patients) 8

Epidemiology

• ESBL prevalence varies significantly by geographic region 4
• Higher rates are observed in Asia, Latin America, Middle East compared to North America and Europe 4
• In healthcare settings, ESBL prevalence is highest in intensive care units (up to 79%), followed by oncology units (75%), and medical/surgical wards (50-54%) 5
• The prevalence of ESBL-producing bacteria has steadily increased over time 4

Laboratory Detection

• ESBL-producing organisms are typically identified through antimicrobial susceptibility testing, with specific patterns of resistance to certain beta-lactam antibiotics 6
• The Clinical and Laboratory Standards Institute (CLSI) states that routine ESBL testing is no longer necessary before reporting results when using newer interpretive criteria for cephalosporins 6
• ESBL testing remains valuable for epidemiological and infection control purposes 6

Treatment Approaches

• Carbapenems are the treatment of choice for serious infections caused by ESBL-producing organisms 7, 1, 2
• For uncomplicated infections, alternative treatments including fosfomycin, nitrofurantoin, and aminoglycosides may be used, depending on susceptibility and infection type 7
• Beta-lactam/beta-lactamase inhibitor combinations may be of value in certain situations, but supporting evidence is limited 2
• Newer agents such as ceftazidime-avibactam have activity against ESBL-producing organisms and may be valuable for treating infections to preserve carbapenems 4
• Tigecycline, polymyxins, and fosfomycin have substantial antimicrobial activity against ESBL-producing Enterobacteriaceae and merit further evaluation 2

Prevention and Control

• Active surveillance in high-risk patients can help identify colonization and prevent dissemination of ESBL-producing organisms 7
• Judicious use of antibiotics is essential to limit selection pressure and emergence of resistance 1, 5
• Implement appropriate infection control measures to control the spread of these strains in healthcare settings 5
• Reduce patient-to-patient transmission via the inanimate environment, hospital personnel, and medical equipment 2

Treatment Considerations Based on Infection Site

• For community-acquired intra-abdominal infections (CA-IAIs), agents with a narrower spectrum of activity are preferred, but in patients at risk for ESBL infections, anti-ESBL-producer coverage may be warranted 4
• For healthcare-associated intra-abdominal infections (HA-IAIs), antibiotic regimens with broader spectra of activity are preferred 4
• In the setting of high ESBL prevalence, extended use of cephalosporins should be discouraged and limited to pathogen-directed therapy 4