1986 Volume 39 Issue 7 Pages 1879-1887
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.
1. 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 7.4mg/7.4mg/kg to 11.8mg/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/25.85mg/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%.
2. 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.
3. 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 μg/ml occurring at the end of the infusion, and then the concentration decreased to 13.9 μg/ml in 0.5 hour, 8.9 μg/ml in 1 hour, 2.8 μg/ml in 2 hours, 0.63 μg/ml in 4 hours and 0.14 μg/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 μg/ml for 5 to 7 hours. The concentration of MK-0787 in the pus of this patient was 3.8 μg/ml at the end of the infusion on the 3rd day. Concentrations of MK-0787 in cerebrospinal fluid in 1 patient with purulent meningitis, at 30 minutes after a 30-minute intravenous drip infusion of 25.85 mg/25.85 mg/kg, were 14.4 μg/ml on the 1st day, 8.0 μg/ml on the 2nd day, and 5.4 μg/ml after a reduction of the dosage to 12.9 mg/12.9 mg/kg on the 2nd day. The MBC of MK-0787 against E. coli isolated from this patient was 0.39 μg/ml with an inoculum of 106 colonyforming units/ml.
4. The above results suggest that MK-0787/MK-0791 at a dosage of about 10 mg/10 mg/kg 3 or 4 times daily given by a 30-60-minute drip infusion will be effective in the treatment of infections other than purulent meningitis, and that it will be a very useful new antibiotic, with an extremely broad and strong antibacterial activity for the treatment infections in children having acute and progressing clinical courses. As far as purulent meningitis is concerned, however, further investigation will be required to evaluate the usefulness of MK-0787/MK-0791.
