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Beta-lactamase stability of imipenem
Abstract:
The beta-lactamase stability and interactions of imipenem were analysed in comparison with those of cefazolin, cefuroxime, cefoxitin, cefotaxime, ceftazidime, mezlocillin, piperacillin and penicillin G for a set of representative beta-lactamases. These enzymes included penicillinases such as those obtained from Staphylococcus aureus, Escherichia coli and other Enterobacteriaceae (TEM-1 and similar enzymes) (group A); cephalosporinases produced by Esch. coli (Amp C type), Serratia liquefaciens, Enterobacter cloacae, Pseudomonas aeruginosa (group B); and beta-lactamases produced by Klebsiella spp., Proteus vulgaris and Bacteroides fragilis and with a high hydrolytic activity for the newer cephalosporins (group C). Enzymes of group A were demonstrated to be highly active against penicillins and also against the early cephalosporins; enzymes of group B showed hydrolytic activity for all other tested compounds, including the newer cephalosporins and cephamycins, but not imipenem, whereas enzymes of group C were highly active against the new cephalosporins but not against cephamycins and imipenem. In conclusion, imipenem shows a moderate affinity for all these enzymes but no detectable hydrolysis.
Insights
Imipenem demonstrates stability against various beta-lactamase enzymes. Unlike other antibiotics, imipenem showed no detectable hydrolysis, indicating its effectiveness against resistant bacteria.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Beta-lactamase enzymes confer resistance to beta-lactam antibiotics.
- Understanding antibiotic-beta-lactamase interactions is crucial for combating antimicrobial resistance.
Purpose of the Study:
- To compare the stability and interactions of imipenem with various beta-lactamases against other beta-lactam antibiotics.
- To evaluate imipenem's resistance profile to different classes of beta-lactamase enzymes.
Main Methods:
- Analysis of imipenem's interaction with representative beta-lactamases (penicillinases, cephalosporinases, and novel beta-lactamases).
- Comparative study with cefazolin, cefuroxime, cefoxitin, cefotaxime, ceftazidime, mezlocillin, piperacillin, and penicillin G.
Main Results:
- Group A enzymes (penicillinases) hydrolyzed penicillins and early cephalosporins.
- Group B enzymes hydrolyzed newer cephalosporins and cephamycins but not imipenem.
- Group C enzymes hydrolyzed newer cephalosporins but not cephamycins or imipenem.
- Imipenem exhibited moderate affinity but no detectable hydrolysis by any tested beta-lactamase.
Conclusions:
- Imipenem demonstrates broad stability against a range of clinically significant beta-lactamases.
- Imipenem's resistance to hydrolysis suggests its potential utility against infections caused by beta-lactamase-producing bacteria.