From the FDA Drug Label
ZERBAXA demonstrated in vitro activity against Enterobacteriaceae in the presence of some extended-spectrum beta-lactamases (ESBLs) and other beta-lactamases of the following groups: TEM, SHV, CTX-M, and OXA. In ZERBAXA clinical trials, some isolates of Enterobacteriaceae with minimum inhibitory concentration to ZERBAXA of ≤2 mcg/mL produced beta-lactamases. These isolates produced one or more beta-lactamases of the following enzyme groups: CTX-M, OXA, TEM, or SHV
- CTX-M is a type of extended-spectrum beta-lactamase (ESBL) that can be produced by some bacteria, including Enterobacteriaceae.
- ZERBAXA has demonstrated in vitro activity against some Enterobacteriaceae that produce CTX-M beta-lactamases 1.
- However, the clinical significance of this activity is not fully established, and culture and susceptibility information should be considered when selecting or modifying antibacterial therapy.
From the Research
Infections caused by CTX-M-producing bacteria typically require treatment with carbapenems, such as meropenem or imipenem, due to their high resistance to many beta-lactam antibiotics. The CTX-M family of extended-spectrum beta-lactamase (ESBL) enzymes is produced by certain bacteria, particularly Enterobacteriaceae like E. coli and Klebsiella pneumoniae, and has become the most prevalent type of ESBLs globally, with over 170 variants identified 2. These enzymes confer resistance to many beta-lactam antibiotics, including penicillins, most cephalosporins, and aztreonam, but not carbapenems.
Key Considerations
- CTX-M enzymes are named for their enhanced ability to hydrolyze cefotaxime (CTX) and were first discovered in Munich (M) 3.
- The rapid spread of CTX-M genes is concerning because they are often carried on mobile genetic elements like plasmids that can transfer between bacteria, contributing significantly to the global antimicrobial resistance crisis 4.
- Infections caused by CTX-M-producing bacteria can be challenging to treat, and the choice of antibiotic should be guided by susceptibility testing, with carbapenems being a preferred option 5, 6.
Treatment Options
- Carbapenems, such as meropenem or imipenem, are generally the preferred treatment option for infections caused by CTX-M-producing bacteria 2.
- Alternative treatment options may include ceftazidime-avibactam, piperacillin-tazobactam (in certain situations), or aminoglycosides, based on susceptibility testing 5, 6.
- The use of cephalosporins or fluoroquinolones as empirical therapy is associated with a higher mortality rate and may need to be changed more frequently 3.
Epidemiology and Risk Factors
- CTX-M-producing E. coli strains are more resistant to multiple antibiotics than non-CTX-M E. coli strains 4.
- Independent risk factors for CTX-M E. coli isolation include male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole 4.
- Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms 4.