[A preclinical and clinical study of cefmenoxime in newborns].

ABSTRACT

1. Cefmenoxime (CMX) was administered with a dosage regimen of 20-25 mg/kg, 2-3 times daily (40-75 mg/kg/day) by intravenous drip over 30 minutes to 9 neonates with bacterial infections including purulent meningitis and septicemia. Clinical responses to the treatment were excellent in 7 and poor in 2. Bacteriological responses were "eradication of pathogens" from 8 of them except another patient with an infection due to Staphylococcus aureus. 2. Adverse reactions to CMX were observed in 6 of 18 neonates treated with the drug diarrhea, oral thrush, and the elevation of S-GOT, S-GPT, LDH and alkaline phosphatase. None of the reactions, however, necessitated the discontinuation of the treatment. 3. Changes in blood concentrations of CMX in neonates with ages between 0 and 30 days were followed. These subjects included 16 mature neonates and 10 neonates with low birth weights. Intravenous drip infusion of 20 mg/kg of CMX over 30 minutes was immediately followed by peak blood CMX concentrations of 34.6-72.7 mcg/ml (mean +/- S.D. 50.4 +/- 11.3 mcg/ml) in the mature neonates, and 22.3-78.2 mcg/ml (55.5 +/- 16.5 mcg/ml) in the neonates with low birth weight. Blood half-lives of the drug in the mature neonates were in the range from 1.7 to 20.7 hours (5.9 +/- 6.6 hours) in subjects with ages of 0-3 days, and 1.1-3.5 hours (2.0 +/- 0.8 hours) in subjects of 4-25 days. In neonates with low birth weight, they were 3.4-10.2 hours (7.2 +/- 2.7 hours) in subjects of 0-2 days, and 1.4-5.5 hours (3.0 +/- 1.5 hours) in subjects of 4-30 days. In other words, the blood half-lives of the drug tended to be longer in younger subjects. 4. Concentration of CMX in cerebrospinal fluid (CSF) were determined in a patient in acute stage with purulent meningitis caused by Mycoplasma hominis. Intravenous drip infusion of 80 mg/kg of CMX over 30 minutes was followed by CSF concentrations of 7.7-15.5 mcg/ml. 5. MICs of CMX for clinical isolates were determined. The drug was proved to have excellent antibacterial activities against Escherichia coli (3 strains) and group B hemolytic streptococci (2 strains) and these MICs were comparable to those of cefotaxime. The MIC of CMX for S. aureus (1 strain) was high at 25 mcg/ml with an inoculum size of 10(8) CFU/ml. This MIC value of CMX was higher than that of cefmetazole.