[Morphological response of urinary bacteria to ceftibuten]

The morphological response of urinary Gram-negative bacteria to ceftibuten (CETB) was investigated in four patients with urinary tract infections (one patient: acute uncomplicated cystitis, three patients: chronic complicated urinary tract infection). The daily dose of CETB was 400 mg administered orally and the durations were 3 days for the acute uncomplicated cystitis case and 5 days for the chronic complicated urinary tract infection cases. In the four patients, changes in urinary CETB concentrations, viable bacterial counts, and morphology of the bacteria were studied after the initial administration. The urinary concentrations of CETB were 7.38-60.3 micrograms/ml at one hour after the first administration. The urinary viable cell counts were 1-5 x 10(7) cells/ml before administration, but they were reduced to 1-3 x 10(3) cells/ml at one hour after the first oral administration. Morphological changes of bacteria: Under phase contrast microscopy, filamentous debris and spherical bacteria with severe body damage were observed at 30 minutes after the first administration. By transmission electron microscopy, the cell wall of the filamentous bacteria showed a number of projections with formation of vacuolar structures in the space between the cell wall and the irregularly-shaped cytoplasm. According to the Japanese UTI criteria, the efficacy rate was 100% in the 4 patients. Neither side effect nor abnormal laboratory result was observed in any patient.

The morphological changes of the bacteria suggested that CETB, in vivo, bounds not only penicillin-binding protein (PBP)-3 but also PBP-1.