Abstract
Basic and clinical studies on fosfomycin for intravenous injection (FOM-Na) were performed, and the results obtained were summarized below.
1) Antibacterial spectrum
The antibacterial activity of FOM-Na against gram-positive and gram-negative bacteria could not be said to be remarkably good.
2) Effect of inoculum size on the antibacterial activity
The influence of inoculum size of clinical isolates upon MIC of FOM-Na was studied. As a result, it was revealed that the MIC of FOM-Na was mostly more than 100μg/ml in the original solution, while 1, 000 times diluted solution, when dealing with Staphylococcus aureus and Pseudomonas aeruginosa in particular, revealed a conspicuously low value.
3) Concentrations in blood and urine
Moni-trol serum was taken as a standard for determination. The result obtained with cup method showed that the blood levels has reached peak level 30 minutes after intravenous administration of 1, 000 mg of FOM-Na with an average figure of 51.7μg/ml, which value was found fairly persistent with 5.6μg/ml still registered even 6 hours later. The concentration in urine showed a similar tendency to that in blood with a peak reached 30 minutes after administration and with an average of 3, 840μg/ml registered. Such a high concentration as 297μg/ml was retained even after 6 hours. The urinary recovery rate within 6 hours after administration was 88.1%, revealing a pattern characteristic of renal excretion.
4) Concentrations in organs
In a group of 3 rats of SD strain which was given 20 mg per kg of body weight the level was the highest in the kidney followed by serum, lungs, heart, spleen, muscle, liver and brain in order. Similarly, the distribution of FOM-Na into bile reached a peak 30 minutes after intravenous administration of 20 mg per kg of body weight with 7.4 μg/ml registered. The concentration of around 5.0μg/ml was maintained for 4 hours following administration.
5) Metabolism in vivo
Metabolism of FOM-Na in vivo was studied with human urine. Bioautogram was prepared by thin layer chromatography using one solvent system. As a result, FOM-Na was found not to be metabolized in vivo.
6) Clinical result
FOM-Na was used in the treatment of 3 hospitalized patients with surgical infections. Each patient received intravenous injection of 1.0 g of FOM-Na in the morning and in the evening. The medication lasted in one patient for 7 days and in two others for 5 days with the result that favorable effect was obtained in 2 out of 3 patients. In all the cases treated no particular noteworthy side effects were observed.
