Cefatrizine과 Clavulanic acid 병합제의 항균작용의 향상

Abstract

Background : β-lactamase play an important role in bacterial resistance against β-lactamase antibiotics. The resistant strains due to the β-lactamases including extended spectrum β-lactamase were susceptible to a combination of cefatrizme (CTRZ) and clavulanic acid (CV), a oral cephalosporin and a β-lactamase inhibitor. We studied properties of β-lactamase inhibition by CV and proposed a concept that the controlled dosing of CTRZ and CV combination can produce more effective synergistic antibacterial activity.

Methods : Inhibition activities of CTRZ and CV against various plactamases were determined by IC?? and effects of CV exposure on antibacterial activity of CTRZ and CV combination were estimated by postantibiotic effects (PAEs), post β-lactamase inhibitor effects (PLIEs), bactericidal effects and in vitro simulation bactericidal effects.

Results : The class A and extended spectrum plactamases were inhibited by CV. PAEs and PLIES were shown to Escherichia coli EB13, Klebsiella pneumoniae EB40 and Moraxella catarrhalis 6012. The PLIEs were prolonged more than the corresponding PAEs. CV-exposed strains were rapidly killed and delayed in regrowth compared to the unexposed strains. The sequential dosing of CTRZ (250 mg) two hours after CTRZ (250 mg) plus CV (250 mg) enhanced antibacterial activity than simultaneous dosing of CTRZ (500 mg) and CV (250 mg) against E.

Coli EB13 in in vitro simulation bactericidal effects.

Conclusion : When a combination of CTRZ and CV was used in human, the controlled-release combination to maintain long CTRZ plasma levels above a cntical concentration was useful for treatment of β-lactamase producing bacterial infections.