lab meeting presentation by 조회숙, talk about some beta-lactomease

1. βeta-Lactamase Inhibitors

2. contents Clavulanicacid: a beta-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. Tazobactam Sulbactam Oxapenem NXL 104 BAL 30376 LK-157 BLI-489 CP3242 SA-1-204

3. Clavulanicacid Natural product of Streptomyces clavuligerus Prevent the destruction of substrates of enzymes Clavulanic acid + TEM-2-β-lactamases=acyl enzyme yield a transiently inhibited form act as enzyme-substrate complex

4. Tazobactam Inhibitory activity of CTX-M type β-lactamases: Tazobactam > clavulanic acid (10-fold) SHV-1- tazobactam complex acyclic form of tazobactam attached to Ser70 acyclic form of 5-atom vinyl carboxylic acid fragment attached to Ser130-OH in the inactive species. Acylation of Ser130Gly β-lactamase by Tazobactam inactivation proceeds independent of any additional covalent interaction

5. Sulbactam Clavulanicacid = Sulbactam Cephalosporinases< penicillinases or broad-spectrum β-lactamases However, the enzyme classes was not as great as observed with clavulanic acid sulbactam > cephalosporinases > clavulanicacid In extensive studies: E. coli TEM-2 β-lactamase hydrolysis of sulbactam observed Sulbactam able to inhibit the most common forms of β-lactamase not able to interact with AmpCcephalosporinase

6. Oxapenem Oxygen-containing ring fused to β-lactam ring found to be potent β-lactamase inhibitor but have poor stability Oxapenems reduced MICs for ceftazidime against class C hyperprodut Ceftazidime+AM-112 ->ESBL producing E. coli strains AM-114 and AM-115->class A enzymes AM-113 and AM-114->class C enzymes

7. NXL 104 NXL 104 and ceftazidime ->class A and class C- producing Enterobacteriaceae members MICs of ceftazidime/AVE 1330 A for Enterobacteriaceae were at least eight fold lower than those of ceftazidime alone

8. BAL 30376 BAL 30376 a novel beta-lactamase inhibitor a combinationofBAL 0019764 BAL 30376-f and BAL30376-v more active against MDR K.Pneumoniaecompared to Cefepime but slightly less active than imipenem. Good activity against Enterobacteriaceae non-fermentive Gram-negative bacteria

9. LK-157 LK-157 + cefotaxime or cefepime= activity found comparable to that of tazobactam LK-157 decreased the MICs of aztreonam, ceftazidime, and cefuroxime B. fragilis (8- to ≥128-fold) β-lactamase-producing Enterobacteriaceae members (up to ≥64-fold)

10. BLI-489 BLI-489 is activity against molecular class A or D enzymes Piperacillin/BLI-489 combination showed potent in vitro activity against diverse β-lactamase producers

11. CP3242 Metallo- β-lactamase (MBL) inhibitor and competitively inhibits both IMP-1 and VIM-2 Lowered the MICs of β-lactams against MBL-producing E. coli transformants Novel competitive MBL inhibitor can be effective against MBL-producers in combination with β-lactam antibiotics

12. SA-1-204 Effective against SHV producingE. coli strains piperacillin/SA-1-204 was more potent than piperacillin/ tazobactam against strains bearing blaSHV-1

13. Thank you for your patient Any Question