Abstract
Bacteriological, pharmacokinetic and clinical studies on SY5555 dry syrup (powder which is dissolved before use), a new penem antibiotic for oral use, were performed. The following results were obtained.
1. Antibacterial activities
MICs of SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) were determined against clinically isolated Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus inflenzae, Moraxella catarrhalis, Escherichia coli and Enterobacter cloacae at a dose of 106 CFU/ml. MICs of SY5555 against S. aureus, CNS, S. pneumoniae, S. pyogenes, H. influenzae, M. catarrhalis, E. coli and E. cloacae were 0.2, 0.2, 0.2, ≤0.025, 0.78, 0.2, 0.78 and 3.13μg/ml, respectively, showing excellent antibacterial effects on these pathogens. Although the effects of SY5555 against H. influenzae and E. coli were slightly inferior to those of CPDX and CFDN, the drug showed the most excellent antibacterial effect on other strains as compared with the control drugs.
2. Absorption and excretion
In this study, plasma concentrations and urinary recovery rates were examined after administration of SY5555 at doses of 5 and 10 mg/kg (potency) after meals. With both 5 and 10 mg/kg doses, peak plasma concentrations were reached 1 hour after administration, at 0.25-2.61μg/ml (mean 1.47μg/ml) and 1.08-2.17μg/ml (mean 1.74μg/ml), respectively. The plasma levels rapidly decreased to 0.06-0.19μg/ml (0.12μg/ml) and 0.0503-0.0637μg/ml (0.057μg/ml) after 6 hours. The half-lives 1.12 hours in the 5 mg/kg group and 1.0 hour in the 10 mg/kg group. The urinary recovery rates were determined in the first 8 hours after administration in the 5 mg/kg and 6 hours in the 10 mg/kg group, and the values were as low as 1.05-12.3% and 1.6-4.33%, respectively.
3. Clinical results
The clinical responses were examined in a total of 73 cases including 4 acute pneumonia, 13 acute bronchitis, 11 tonsillitis, 3 pharyngitis, 12 scarlet fever, 2 pertussis, 6 urinary tract infection, 6 otitis media, 7 lymphadenitis, 2 staphylococcal scalded skin syndrome, 2 phlegmon, 4 impetigo and 1 purulent parotitis. The treatment was effective or better in 66 of 70 cases with an efficacy rate of 94.3% (3 undeterminable cases were excluded). Bacteriological effects were examined during the clinical course for detected or suspected pathogens found before administration of SY5555. The effects were determined in 50 cases including 7 cases of polymicrobacterial infections, 57 strains in total. Eight strains, however, persisted, hence the overall eradication rate was 86.0%. Because of the persistence of eight strains, the bacteriological efficacy rate was 84.0% (42/50). Except for mild watery stool which appeared in 1 case, no adverse reactions or abnormal laboratory test values were observed in any case.
