This document discusses various beta-lactamase inhibitors that are used in combination with beta-lactam antibiotics to overcome antibiotic resistance. It describes several natural and synthetic inhibitors including clavulanic acid, tazobactam, sulbactam, oxapenems, NXL 104, BAL 30376, LK-157, BLI-489, CP3242, and SA-1-204. These inhibitors work by preventing beta-lactamase enzymes from breaking down beta-lactam antibiotics, thereby restoring the antibiotics' effectiveness against resistant bacteria. The document compares the inhibitory activities and spectra of each inhibitor.

1. βeta-Lactamase Inhibitors

2. contentsClavulanicacid: a beta-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance.TazobactamSulbactamOxapenemNXL 104BAL 30376LK-157BLI-489CP3242SA-1-204

3. ClavulanicacidNatural product of Streptomyces clavuligerusPrevent the destruction of substrates of enzymesClavulanic acid + TEM-2-β-lactamases=acyl enzymeyield a transiently inhibited formact as enzyme-substrate complex

4. TazobactamInhibitory 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 Tazobactaminactivation proceeds independent of any additional covalent interaction

5. SulbactamClavulanicacid = SulbactamCephalosporinases< penicillinases or broad-spectrum β-lactamasesHowever, the enzyme classes was not as great as observed with clavulanic acidsulbactam > cephalosporinases > clavulanicacidIn extensive studies: E. coli TEM-2 β-lactamasehydrolysis of sulbactam observed Sulbactamable to inhibit the most common forms of β-lactamase not able to interact with AmpCcephalosporinase

6. OxapenemOxygen-containing ring fused to β-lactam ringfound to be potent β-lactamase inhibitor but have poor stabilityOxapenems reduced MICs for ceftazidime against class C hyperprodutCeftazidime+AM-112 ->ESBL producing E. coli strainsAM-114 and AM-115->class A enzymesAM-113 and AM-114->class C enzymes

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

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

9. LK-157LK-157 + cefotaxime or cefepime= activity found comparable to that of tazobactamLK-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-489BLI-489 is activity against molecular class A or D enzymesPiperacillin/BLI-489 combination showed potent in vitro activity against diverse β-lactamase producers

11. CP3242Metallo- β-lactamase (MBL) inhibitor and competitively inhibits both IMP-1 and VIM-2Lowered the MICs of β-lactams against MBL-producing E. coli transformantsNovel competitive MBL inhibitor can be effective against MBL-producers in combination with β-lactam antibiotics

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

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