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[Enzymologic aspect of piperacillin combinations]
Abstract:
Like all penicillins, piperacillin exhibits some susceptibility to beta-lactamases of the penicillinase type, including those produced by Staphylococcus aureus and the TEM, OXA and CARB enzymes isolated from Gram-negative bacilli. Piperacillin is very slightly hydrolyzed by cephalosporinases, which makes it similar to 3rd generation cephalosporins. When tested with Enterobacter cloacae GN 5797 and Pseudomonas aeruginosa NTC 8303, two strains which produce inducible cephalosporinases, piperacillin had moderate inductive activity compared to cefoxitin, a potent inducer. Induction was very low with Enterobacter, but the drug was slightly more sensitive to Pseudomonas. Inhibition of this type of beta-lactamase synthesis was very strong when piperacillin was combined with amikacin and weaker when it was combined with pefloxacin. The piperacillin-amikacin combination prevented the development of piperacillin-resistant mutants of Enterobacter and Pseudomonas and, probably, of all Gram-negative bacilli. In our tests, the piperacillin-pefloxacin combination was of interest only against Enterobacter, and probably against all enterobacteria, since Pseudomonas mutants that resist pefloxacin are fairly easily obtained in vitro.
Insights
Piperacillin shows susceptibility to beta-lactamases but is only slightly hydrolyzed by cephalosporinases. Combining piperacillin with amikacin effectively prevents the development of resistant Gram-negative bacilli mutants.
Area of Science:
- Microbiology
- Pharmacology
- Antibiotic Resistance
Background:
- Piperacillin, a penicillin antibiotic, exhibits susceptibility to various beta-lactamases, including those from Staphylococcus aureus and Gram-negative bacilli.
- Its hydrolysis by cephalosporinases is minimal, similar to third-generation cephalosporins.
- Inducible cephalosporinases produced by Enterobacter cloacae and Pseudomonas aeruginosa pose a challenge for antibiotic efficacy.
Purpose of the Study:
- To evaluate piperacillin's susceptibility to beta-lactamases and its inductive activity on cephalosporinases.
- To assess the efficacy of combining piperacillin with amikacin or pefloxacin in preventing antibiotic resistance.
Main Methods:
- Testing piperacillin's susceptibility to penicillinase-type beta-lactamases.
- Evaluating piperacillin's inductive activity on cephalosporinases from Enterobacter cloacae and Pseudomonas aeruginosa.
- Assessing the effect of piperacillin-amikacin and piperacillin-pefloxacin combinations on the development of resistant mutants.
Main Results:
- Piperacillin demonstrated susceptibility to penicillinase-type beta-lactamases but minimal hydrolysis by cephalosporinases.
- Piperacillin exhibited moderate inductive activity on cephalosporinases, with lower induction in Enterobacter compared to Pseudomonas.
- The piperacillin-amikacin combination strongly inhibited beta-lactamase synthesis and prevented the emergence of resistant mutants in Enterobacter and Pseudomonas.
- The piperacillin-pefloxacin combination showed efficacy against Enterobacter but was less effective against Pseudomonas due to easily acquired resistance.
Conclusions:
- Piperacillin's activity is influenced by beta-lactamase production, with varying inductive effects on cephalosporinases.
- Combination therapy with amikacin is highly effective in preventing piperacillin resistance in Gram-negative bacilli.
- Pefloxacin combination offers limited benefit against Pseudomonas resistance due to rapid in vitro development of resistance.