An open clinical study of tebipenem pivoxil in children with bacterial pneumonia

We conducted an open clinical study of a new oral carbapenem antibacterial agent, tebipenem pivoxil (TBPM-PI), in pediatric patients with bacterial pneumonia to assess efficacy, safety, medication compliance, and pharmacokinetics. Dosage and administration were 4 mg/kg bid or 6 mg/kg bid, and treatment was 7 days. Clinical efficacy in 59 subjects was 98.3% (58/59), and efficacy by treatment group was 100% (35/35) in the 4 mg/kg bid group and 95.8% (23/ 24) in the 6 mg/kg bid group. In 10 subjects from whom sputum could be collected, sputum had disappeared by the end of administration. Bacteriological eradication was 100% (16/16). Isolation frequency was high for Streptococcus pneumoniae (5 strains) and Haemophilus influenzae (9 strains) as causative organisms. The incidence of drug-related adverse reactions associated with subjective symptoms/objective findings in 66 subjects for safety analysis was 40.0% (16/40) in the 4 mg/kg bid group and 30.8% (8/26) in the 6 mg/kg bid group. The incidence of drug-related adverse reactions associated with abnormal changes in laboratory data was 10.0% (4/40) in the 4 mg/kg bid group and 11.5% (3/26) in the 6 mg/kg bid group, showing no increase in incidence with dosage increase. Common adverse drug reactions included stools watery, mushy stool, loose bowel, and platelet count increase. No severe or serious adverse drug reactions were seen. Drug compliance in both groups was 89.4% (59/66), and no administration was judged "Hard to take" or "Unable to take." Concerning pharmacokinetics in 65 subjects for whom plasma TBPM concentrations could be measured, C_max and AUC_0-24h increased with dosage. No difference in T_max or t_1/2 depended on dosage. Results suggest that TBPM-PI could be expected to show high efficacy at 4 mg/kg bid in pediatric patients with bacterial pneumonia and no significant safety problems. High efficacy was shown in patients requiring a high dose and given 6 mg/kg bid despite high CRP, WBC, and detection of resistant strains, and administration of 6 mg/kg bid was judged to be useful depending on symptom and severity.