Background : The purpose of this study was to determine the synergistic activity of cefatrizme (CTRZ) combined with clavulanic acid (CV) against extended-spectrum β-lactamase (ESBL) producing strains.
Methods : Minimum inhibitory concentration was deterinined by the standard agar dilution method as recommended by the Japan Society of Chemotherapy. CTRZ/CV was evaluated for in vivo efficacy in a variety of experimental intra-peritoneal infections as well as in localized kidney and lung infections in mice.
Results : The addition of 0.012 ㎍/mL of CV markedly increased the in vitro antibacterial activity of CTRZ against β-lactamase-producmg strains including ESBL-producing strains and the most effective combination ratio was shown to be between 8:1 and 2:l. The in uivo efficacy of CTRZ and CV in combination was determined using experimental intraperitoneal infections in mice with ESBL-producing Exherichia coli EB13 and Klebsiella pneumoniae EB40 and the inost effective combination ratio was shown to be between 2:1 and 1:2.
CTRZ/CV at a ratio of 2:1 showed baetericldal activity against β-lactamase-producing strains including ESBL-producing strains and the therapeutic efficacy of CTRZ/CV against intraperitoneal infection in mice with E. colz EB13, K. pneumoniae EB40 and Proteus vulgaris 5 was superior to that of CTRZ. in respiratory tract infection in mce due to K. pneumoniae EB40, CTRZ/CV at a ratio of 2:1 was more effective than CTRZ and also more efficacious than CTRZ in urinary tract infection in mice due to E. coli EB13.
Conclusion : CTRZ/CV combination at a ratio of 2:l is a useful drug for the treatment of infection caused by β-lactamase-producing strains including ESBL-producing strains.