[Fundamental and clinical evaluation of imipenem/cilastatin sodium in the field of pediatrics].
A combination drug of imipenem (MK-0787), a new carbapenem antibiotic, and cilastatin sodium (MK-0791) at a ratio of 1:1 was used to treat infections in 8 children, and the concentrations of MK-0787 were determined in plasma, urine and pus of 1 patient and in cerebrospinal fluid of another patient. Eight patients, aged 2 months to 12 years (males: 3, females: 5), were treated with MK-0787/MK-0791. They consisted of 3 with urinary tract infections (causative organisms: E. coli, K. oxytoca plus E. faecalis, and unknown), and 1 patient each with pneumonia (H. influenzae), enteritis (Salmonella C1), cellulitis (S. aureus), purulent lymphadenitis (unknown) and purulent meningitis (E. coli). The dose, ranging from 7.4 mg/7.4 mg/kg to 11.8 mg/11.8 mg/kg, 3 or 4 times daily, was administered by a 30-minute or 60-minute intravenous drip infusion for 5 to 11 days. To the patient with purulent meningitis, however, 25.85 mg/25.85 mg/kg on the 1st day and 12.9 mg/12.9 mg/kg from the 2nd day were administered 4 times daily. Clinical responses in urinary tract infections were excellent in 2 and good in 1, and responses in pneumonia, enteritis, cellulitis, purulent lymphadenitis and purulent meningitis were excellent, good, good, excellent and poor, respectively. The efficacy rate in a total of 8 patients was 87.5%. As adverse reactions, a rash was observed in one patient and a convulsion in another. The rash disappeared after discontinuation of the administration of the drug and the convulsion stopped after a reduction of the dosage. As abnormal laboratory findings, slight prolongation of the prothrombin time was observed in 1 patient, but no bleeding tendency was noted. When MK-0787/MK-0791 (500 mg/500 mg, or 8.7 mg/8.7 mg/kg) was given by a 60-minute intravenous drip infusion to a 12-year-old boy with cellulitis, the peak plasma concentration of MK-0787 was 31.4 micrograms/ml occurring at the end of the infusion, and then the concentration decreased to 13.9 micrograms/ml in 0.5 hour, 8.9 micrograms/ml in 1 hour, 2.8 micrograms/ml in 2 hours, 0.63 microgram/ml in 4 hours and 0.14 microgram/ml in 6 hours. The half-life was 0.83 hour. These plasma levels provided concentrations exceeding MIC90's against major infective bacteria for 2 hours. The urinary recovery in the first 7 hours was 75.0%, and the urinary concentration was greater than 100 micrograms/ml for 5 to 7 hours.(ABSTRACT TRUNCATED AT 400 WORDS)
D001424:Bacterial Infections / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D015377:Cilastatin; D003521:Cyclopropanes / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004338:Drug Combinations; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D015378:Imipenem; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D012640:Seizures / Q000139:chemically induced; D013845:Thienamycins / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism
D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem