How to diagnose an ESBL (Extended-Spectrum Beta-Lactamase) E. coli infection?

From the Guidelines

Diagnosing an ESBL E. coli infection requires laboratory testing of clinical specimens, specifically through antimicrobial susceptibility testing and phenotypic methods such as the combination disk test, as recommended by recent guidelines 1. The process typically begins with collection of appropriate samples such as urine, blood, wound exudate, or other relevant specimens depending on the suspected site of infection.

• These samples are cultured on standard media to isolate the organism,
• followed by antimicrobial susceptibility testing to guide antibiotic therapy,
• as the results are reported as the minimal inhibitory concentration (MIC), which is the lowest concentration of drug that inhibits the growth of the organism,
• and the interpretation usually categorizes each result as susceptible (S), intermediate (I), and resistant (R) basing on breakpoints established by either the Clinical or Laboratory Standards Institute (CLSI) in the USA or the European Committee for Antimicrobial Susceptibility Testing (EUCAST) in Europe 1. ESBL production is suspected when the isolate shows resistance to third-generation cephalosporins (like ceftriaxone, ceftazidime, or cefotaxime) 1.
• Confirmation of ESBL production is then performed using phenotypic methods such as the combination disk test,
• where cephalosporin disks are used with and without clavulanic acid (a beta-lactamase inhibitor),
• and an increase in the zone of inhibition with the addition of clavulanic acid indicates ESBL production. Automated systems like VITEK or Phoenix can also detect ESBL producers,
• and molecular methods such as PCR can identify specific ESBL genes,
• allowing for proper diagnosis and appropriate antibiotic selection,
• as ESBL-producing organisms are resistant to many commonly used antibiotics including penicillins and cephalosporins,
• often requiring carbapenems or other specialized antibiotics for effective treatment,
• such as ceftolozane/tazobactam and ceftazidime/avibactam, which are two new cephalosporins/beta-lactamase inhibitor combinations approved for IAIs 1. In settings with a high incidence of ESBL-producing Enterobacteriaceae, the extended use of cephalosporins should be discouraged and should be limited to pathogen-directed therapy because of its selective pressure resulting in emergence of resistance 1. The use of rapid molecular tests might reduce the need for broad-spectrum empiric antibiotic therapy 1, and carbapenem-sparing strategies are desirable in settings where resistances are diffused, with alternative regimens using carbapenem-sparing beta-lactam/beta-lactamase inhibitor combinations (BL-BLICs) proposed 1.

From the Research

Diagnosing ESBL E. coli Infections

To diagnose an ESBL (Extended-Spectrum Beta-Lactamase) E. coli infection, several methods can be employed:

• Phenotypic tests, such as the double disk synergy test and modified Hodge test, can be used to detect ESBL production and carbapenemase production in clinical isolates 2.
• Genotypic tests, including PCR screening for ESBL genes and plasmid-mediated AmpC β-lactamases, can also be utilized to identify ESBL-producing organisms 3, 4.
• Antibiotic susceptibility testing can be performed to determine the resistance pattern of the isolate, which can help guide treatment decisions 5, 6, 2.

Characteristics of ESBL E. coli

ESBL-producing E. coli strains often exhibit certain characteristics, including:

• Resistance to extended-spectrum β-lactam antibiotics, such as ceftriaxone and ceftazidime 5, 6.
• Co-production of carbapenemase and ESBL, which can lead to carbapenem resistance 2.
• Dominance of certain clones, such as ST131, which can be highly virulent and successful 3.

Treatment and Management

The treatment of ESBL E. coli infections can be challenging due to the limited effectiveness of certain antibiotics:

• Carbapenems, such as meropenem, are often considered the drugs of choice for treating ESBL-producing organisms 5, 6.
• However, the use of carbapenems can be associated with the emergence of carbapenem-resistant bacterial species 5.
• Alternative treatment options, such as piperacillin-tazobactam, may not always be effective, and their use should be guided by antibiotic susceptibility testing and clinical judgment 6, 3.