Importance of Enterobacterales that Develop Resistance Due to Expanded-Spectrum Beta-Lactamase and Carbapenemase Production

The development of antibiotic resistance is increasing worldwide. Third-generation cephalosporins-resistant Enterobacterales (ESBL-E) and carbapenems-resistant Enterobacterales (CRE) have been placed in the critical category by the World Health Organization on its list of global priority pathogens.
ESBL-E is a group of Enterobacterales bacteria that exhibit resistance to beta-lactams, broad-spectrum beta-lactams, and third-generation cephalosporins. The CTX-M-15 enzyme, responsible for resistance, is the most identified identified in the ESBL-E group bacteria.
In parallel with the increase in infectious diseases caused by the ESBL-E group bacteria, the use of carbapenems increased, resulting in an increase in carbapenem resistance. Carbapenemases are classified into three groups: A, B, and D. OXA (Oxacillin-hydrolyzing carbapenemase) enzymes that form Class D carbapenemases are endemic in Türkiye.
The first CRE strain was detected in the 1980s and soon spread worldwide. Carbapenemase groups A, B, and D are observed in various countries and are even considered endemic in some, such as Türkiye.
At EUCAST (European Committee on Antimicrobial Susceptibility Testing) and CLSI (Clinical and Laboratory Standards Institute) guidelines, the carbapenem group of antibiotics are suggested as preferred agents for the treatment of ESBL-producing Enterobacterales serious infections.
There are three approaches for treating infections caused by carbapenem-resistant Enterobacterales: 1) re-evaluation of treatment options with existing antibiotics (fosfomycin, colistin, tigecycline, such as the use of older antibiotics), 2) treatment with two carbapenems (combination of two different carbapenems), 3) treatment with new β-lactam and beta-lactamase inhibitor combinations or with new antibiotics (Ceftazidime/avibactam, Meropenem/vaborbactam, Plazomicin, Eravacyclin; the use of new antibiotics).
An increase in the prevalence of multidrug-resistant bacterial infections such as CRE and ESBL-E is causing antibiotic resistance to pose a global threat today. An international, multidisciplinary approach is needed to combat this global threat.