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[Interactions of ceftriaxone with beta-lactamases including those which hydrolyze cefotaxime]
Abstract:
As it occurs with most of 3rd generation cephalosporins, ceftriaxone has few, if any, interactions with penicillinase-type beta-lactamases, such as TEM-1, TEM-2 or PIT-2. These poor interactions are characterized by an extremely low hydrolysis, associated to a poor affinity of these compounds for the penicillinases. Conversely, ceftriaxone, as cefotaxime, shows a high affinity for chromosomally-mediated cephalosporinases (indole-positive Proteus, Enterobacter, Pseudomonas...), which is characterized by Ki values ranging from about 0.05 to 1 microM. Within these beta-lactamases, the hydrolysis of ceftriaxone, as that of cefotaxime, is always low, but significant. Then few beta-lactamases are able to hydrolyze more efficiently cefotaxime, as cefuroxime, such as those produced by P vulgaris and K oxytoca. Within these enzymes, ceftriaxone is also hydrolyzed, in a way quite similar to that of cefotaxime.
Insights
Ceftriaxone shows low interaction with penicillinase-type beta-lactamases but high affinity for chromosomally-mediated cephalosporinases. Its hydrolysis is low but significant against these enzymes, similar to cefotaxime.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Context:
- Third-generation cephalosporins, like ceftriaxone, are crucial antibiotics.
- Beta-lactamase enzymes confer bacterial resistance to antibiotics.
- Understanding antibiotic-beta-lactamase interactions is key to combating resistance.
Purpose:
- To investigate the interaction of ceftriaxone with different classes of beta-lactamase enzymes.
- To quantify the hydrolysis rates and binding affinities of ceftriaxone.
Summary:
- Ceftriaxone exhibits minimal hydrolysis and low affinity for penicillinase-type beta-lactamases (e.g., TEM-1, TEM-2, PIT-2).
- Conversely, ceftriaxone demonstrates high affinity (Ki: 0.05–1 µM) and significant, albeit low, hydrolysis by chromosomally-mediated cephalosporinases (e.g., from indole-positive Proteus, Enterobacter, Pseudomonas).
- Hydrolysis of ceftriaxone by certain cephalosporinases, like those from P. vulgaris and K. oxytoca, is comparable to cefotaxime.
Impact:
- Provides insights into ceftriaxone's activity spectrum against resistant bacteria.
- Informs the development of new antibiotics or strategies to overcome beta-lactamase-mediated resistance.
- Contributes to understanding antibiotic pharmacodynamics and resistance mechanisms.