On the kinetic interaction between ceftriaxone and some beta-lactamases

Area of Science:

• Microbiology
• Biochemistry
• Pharmacology

Background:

• Beta-lactam antibiotics, including third-generation cephalosporins like ceftriaxone, are vital in treating bacterial infections.
• Beta-lactamase enzymes are a primary mechanism of bacterial resistance to beta-lactam antibiotics.
• Citrobacter diversus is a bacterial species known to harbor resistance mechanisms.

Purpose of the Study:

• To investigate the activity of beta-lactamases from Citrobacter diversus ULA-27 against ceftriaxone.
• To compare the hydrolytic activity of these enzymes with other known beta-lactamases.
• To understand the role of C. diversus ULA-27 beta-lactamases in resistance to third-generation cephalosporins.

Main Methods:

• Enzyme assays were performed to measure the hydrolysis of ceftriaxone by beta-lactamases from C. diversus ULA-27.
• The activity of these enzymes was compared to beta-lactamases from Enterobacter cloacae, Bacillus cereus, and Mycobacterium fortuitum.
• Hydrolysis of ceftriaxone derivatives (cefotaxime, ceftizoxime) and inhibition assays with cefazolin were conducted.

Main Results:

• Beta-lactamases from C. diversus ULA-27 showed significant hydrolysis of ceftriaxone.
• Ceftriaxone was resistant to hydrolysis by beta-lactamases from E. cloacae and B. cereus.
• Ceftriaxone derivatives were less susceptible to hydrolysis by C. diversus ULA-27 enzymes, correlating with MIC values.

Conclusions:

• Beta-lactamases from Citrobacter diversus ULA-27 play a significant role in the strain's resistance to ceftriaxone.
• The specific activity of these enzymes contributes to the ineffectiveness of third-generation cephalosporins against this strain.
• Understanding these resistance mechanisms is crucial for developing effective antimicrobial strategies.