Clinical and fundamental study on biapenem for complicated urinary tract infections

Abstract

We fundamentally investigated antimicrobial activity of biapenem (BIPM) in urine medium and influence of BIPM on bactericidal activity of neutrophils in order to clarify its in vivo effects against urinary tract infections.
We also investigated clinical efficacy and safety of BIPM for urinary tract infections in order to clarify its usefulness for urinary tract infections.
In the fundamental study, we measured minimum bactericidal concentrations (MBCs) of BIPM against Escherichia coli and Pseudomonas aeruginosa in urine mediums, which had different pH, different magnesium and calcium concentrations. There was no influence of pH, magnecium and calcium concentration on MBCs of BIPM against these two strains. We also studied the influence of BIPM on bactericidal activity measuring superoxide generation of human neutrophils stimulated with phorbol myristate acetate (PM A), E. coli cells or P. aeruginosa cells in the presence or absence of BIPM. Superoxide generation of neutrophils stimulated with PMA or E. coil cells was not enhanced in the presence of BIPM. In contrast, superoxide generation by neutrophils stimulated with P. aeruginosa cells was enhanced in the presence of BIPM.
In the clinical study, we administered 150 mg or 300 mg BIPM twice daily for five days to eleven patients with complicated urinary tract infections. According to the criteria of UTI Committee, clinical efficacy was excellent in one patient, moderate in five patients and poor in one patient. Furthermore, according to the doctor's judgement, clinical efficacy was excellent in two patients, good in four patients, fair in one patient and poor in two patients. Of nine strains isolated, eight strains were eradicated after administration of BIPM.
None had side effect nor abnormal laboratory finding.
These results indicate that BIPM has good in vivo effect, especially against P. aeruginosa, and BIPM is useful for urinary tract infections.