Labile lactamase

Indicahons for combined therapy are now considered to be much fewer than originahy thought. There is also the problem of a chemical or physical incompahbility between two dmgs. Examples where combinahons have an important role to play in anhbacterial chemotherapy were provided earlier (sections 2.3 and 2.9) in which a fi-lactamase inhibitor and an appropriate j3-lactamase-labile penicillin form a single... 

Some combinations of antimicrobials are potentially antagonistic. For example, agents that are capable of inducing /1-lactamase production in bacteria (such as cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem. 

Relatively narrow spectrum against Gram-negative species due to their lability to /3-lactamases Cefazolin... 

High activity against gram-positive bacteria. Low activity against gram-negative bacteria. Acid-labile. Destroyed by [5 lactamase. 60% protein-bound. 

Methylene penems constitute good /3-lactamase inhibitors as their hydrolytic metabolism leads to the formation of 1,4-thiazepines, strengthening the thus-formed acyl-enzyme complex link (see Sections 2.03.6.9 and 2.03.12.4). However, compared to penams, penem sulfones are not as good /3-lactamase inhibitors as their half-lives of hydrolysis are too short, making them labile under physiological conditions <1997BML2217>. 

The synthetic penicillin sulfone [sulbactam, (42) has been shown to act as a p-lactamase inhibitor. The inhibition is based on a similar mechanism as proposed above 62). A prodrug, sultamicillin 43), which combines sulbactam and amoxacillin by labile... 

For example, clavulanic acid inhibits the enzyme 0-lactamase and is therefore able to protect penicillins which are labile to that particular enzyme (Chapter 10). 

Early penicillin (Pen G) was acid labile and could not be administered orally. It was ineffective against many Gram-negative bacteria and was destroyed by P-lactamases. Each of these limitations has been overcome in newer penicillins due to alterations of the chemical structure or the development of adjunct agents such as probenicid and clavulinic acid. These... 

---