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Beta lactamase inhibitors-fx


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

Beta lactamase inhibitors-fx

  1. 1. βeta-Lactamase Inhibitors<br />
  2. 2. contents<br />Clavulanicacid: <br />a beta-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance.<br />Tazobactam<br />Sulbactam<br />Oxapenem<br />NXL 104<br />BAL 30376<br />LK-157<br />BLI-489<br />CP3242<br />SA-1-204<br />
  3. 3. Clavulanicacid<br />Natural product of Streptomyces clavuligerus<br />Prevent the destruction of substrates of enzymes<br />Clavulanic acid + TEM-2-β-lactamases=acyl enzyme<br />yield a transiently inhibited form<br />act as enzyme-substrate complex<br />
  4. 4. Tazobactam<br />Inhibitory activity of CTX-M type β-lactamases:<br />Tazobactam > clavulanic acid (10-fold)<br />SHV-1- tazobactam complex <br />acyclic form of tazobactam attached to Ser70 <br />acyclic form of 5-atom vinyl carboxylic acid fragment attached to Ser130-OH in the inactive species.<br />Acylation of Ser130Gly β-lactamase by Tazobactam<br />inactivation proceeds independent of any additional covalent interaction<br />
  5. 5. Sulbactam<br />Clavulanicacid = Sulbactam<br />Cephalosporinases< penicillinases or broad-spectrum β-lactamases<br />However, the enzyme classes was not as great as observed with clavulanic acid<br />sulbactam > cephalosporinases > clavulanicacid<br />In extensive studies: E. coli TEM-2 β-lactamase<br />hydrolysis of sulbactam observed <br />Sulbactam<br />able to inhibit the most common forms of β-lactamase <br />not able to interact with AmpCcephalosporinase<br />
  6. 6. Oxapenem<br />Oxygen-containing ring fused to β-lactam ring<br />found to be potent β-lactamase inhibitor <br />but have poor stability<br />Oxapenems reduced MICs for ceftazidime against class C hyperprodut<br />Ceftazidime+AM-112 ->ESBL producing E. coli strains<br />AM-114 and AM-115->class A enzymes<br />AM-113 and AM-114->class C enzymes<br />
  7. 7. NXL 104<br />NXL 104 and ceftazidime ->class A and<br /> class C- producing Enterobacteriaceae members<br />MICs of ceftazidime/AVE 1330 A for Enterobacteriaceae were at least eight fold lower than those of ceftazidime alone<br />
  8. 8. BAL 30376<br />BAL 30376 <br />a novel beta-lactamase inhibitor <br />a combinationofBAL 0019764<br />BAL 30376-f and BAL30376-v more active against MDR K.Pneumoniaecompared to Cefepime<br />but slightly less active than imipenem.<br />Good activity against <br />Enterobacteriaceae<br />non-fermentive Gram-negative bacteria<br />
  9. 9. LK-157<br />LK-157 + cefotaxime or cefepime= activity <br />found comparable to that of tazobactam<br />LK-157 decreased the MICs of aztreonam, ceftazidime, and cefuroxime <br />B. fragilis (8- to ≥128-fold) <br />β-lactamase-producing Enterobacteriaceae members (up to ≥64-fold)<br />
  10. 10. BLI-489<br />BLI-489 is activity against molecular class A or D enzymes<br />Piperacillin/BLI-489 combination showed potent in vitro activity against diverse β-lactamase producers<br />
  11. 11. CP3242<br />Metallo- β-lactamase (MBL) inhibitor and competitively inhibits both IMP-1 and VIM-2<br />Lowered the MICs of β-lactams against MBL-producing E. coli transformants<br />Novel competitive MBL inhibitor can be effective against MBL-producers in combination with β-lactam antibiotics<br />
  12. 12. SA-1-204<br />Effective against SHV producingE. coli strains<br />piperacillin/SA-1-204 was more potent than piperacillin/ tazobactam against strains bearing blaSHV-1<br />
  13. 13. Thank you for your patient<br />Any Question<br />