[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Basic and clinical studies on cefditoren pivoxil in pediatric field].

Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained. 1. In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR-PI. Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined. Against other 4 species, MICs of the above 6 agents excluding methicillin were determined. Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S. aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains). These values were equal to or lower than those of conventional cephems and of methicillin. Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains). Also, these values were equal to or lower than those of conventional cephems. 2. When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively. Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient. 3. The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively. Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively. 4. Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy. 5. Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated. 6. Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS)