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Beta-lactamases, beta-lactamase inhibitors, and skin and skin-structure infections
1College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Abstract:
beta-Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus. The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated beta-lactamases were recognized in the Enterobacteriaceae, Haemophilus, and chromosomally mediated beta-lactamases in Klebsiella, and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of beta-lactamases. Clavulanate is a beta-lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit beta-lactamase-producing bacteria and retain activity against Pseudomonas. Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other beta-lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate-amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections.
Insights
Beta-lactamase inhibitors, such as clavulanate and sulbactam, combat bacterial resistance. Combining these inhibitors with antibiotics like amoxicillin and ticarcillin effectively treats infections caused by resistant bacteria.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Beta-lactamases, identified in the 1940s, are a primary mechanism of bacterial resistance, particularly in Staphylococcus aureus.
- The emergence of gram-negative bacteria necessitated understanding plasmid-mediated and chromosomal beta-lactamases in species like Enterobacteriaceae, Haemophilus, Klebsiella, and Bacteroides.
- Resistance to ampicillin and related penicillins by these bacteria highlighted the need for novel therapeutic strategies.
Purpose of the Study:
- To review the development and application of beta-lactamase inhibitors as a strategy to overcome bacterial resistance.
- To highlight the efficacy of specific beta-lactamase inhibitor combinations in treating bacterial infections.
- To present these combinations as viable alternatives for managing cutaneous infections.
Main Methods:
- Review of historical data on beta-lactamase discovery and resistance mechanisms.
- Description of the development of stable beta-lactam compounds (cephalosporins).
- Explanation of the strategy involving beta-lactamase inhibitors, specifically clavulanate and sulbactam, in combination with beta-lactam antibiotics.
Main Results:
- Clavulanate, combined with amoxicillin, inhibits many amoxicillin-resistant organisms.
- Clavulanate and ticarcillin form a parenteral agent effective against beta-lactamase-producing bacteria, including Pseudomonas.
- Sulbactam combined with ampicillin, and suicide inhibitors with other beta-lactams, show efficacy in mixed cutaneous infections.
- Clinical studies confirm the effectiveness of clavulanate-amoxicillin and clavulanate-ticarcillin in skin and skin-structure infections.
Conclusions:
- Beta-lactamase inhibitors represent a crucial advancement in combating bacterial resistance.
- Combinations of beta-lactamase inhibitors with antibiotics offer effective treatment options for various bacterial infections.
- These combination agents provide valuable alternatives for treating cutaneous infections.