β-Lactamase생성균주에 대한 새로운 β-Lactamase Inbitating Compound와 β-lactam항생제와의 병용시 항균효과 = Antimicrobial Activity of the New β-Lactamase Inhibiting compound with β-Lactams against β-Lactamase-Producing Bacteria

다국어 초록 (Multilingual Abstract)

The in vitro and in vivo activities of CH1250, a new β-lactamase inhibiting compound, were compared with the activities of clavulanic acid and sulbactam against 30 β-lactamase-producing bacteria. Broth microdilution susceptibility testing was performed to compare the activities of β-lactamase inhibitors. Serial two fold dilutions of β-lactams were tested alone and in two combinations with β-lactamase inhibitor. CH1250 was more active than clavulanic acid against Acinetobacter calcoaceticus S21, Pseudomonas aerug-nosa GN918, Proteus vulgaris 20, Staphylococcus aureus MS15009/1258, Serratia marcescens 1 when combined with cefotaxime. When combined with amoxicillin, CH1250 was more effective against Citrobacter diversus 2046E. Staphylococcus aureus MS25009/1258, Proteus vulgaris GN76. With ampicillin, CH1250 had an better or simillar activities against Escherichia coli 3455E, Klebsiella aerogenes 1976E, Serratia marcescens 1, Staphylococcus aureus MS15009/1258. The efficacy of ampicillin-CH1250 in treatment of mice with systemic infections produced by Klebsiella aerogenes 1976E, a β-lactamase-producing bacteria, was compared with that of ampicillin, ampicillin-sulbactam. Acute systemic infections in mice were produced by i.p. inoculation of bacterial cultures suspended in 6% mucin. Mice were treated s.c. 1hr after challenge. PD50s of the ampicillin, ampicillin-sulbactam. ampicillin-CH1250 were 334.32, 170.58, 250.5mg/kg, respectively. CH1250 was not more effective than sulbactam in reducing ampicillin doses required to protect mice from infection produced with Klebsiella aerogenes 1976E. The reduction in the 50% protective dose of ampicillin by CH1250 was 23% better than those effected by sulbactam for Klebsiella aerogenes 1976E infection.