1975 Volume 23 Issue 5 Pages 1861-1870
Basic and clinical studies on fosfomycin have been performed, and the results obtained are summarized below.
1) Antibacterial spectrum of fosfomycin : The antibacterial activity against Gram-positive and Gram-negative bacteria could not be found to be remarkably good.
2) Effect of inoculm size on the antibacterial activity : The effect of inoculum size on MIC of fosfomycin was studied. As a result, it was revealed that the MIC of fosfomycin was mostly over 100μg/ml in the original bacterial solution, while it was low in the 1, 000 times diluted solution. This phenomenon was remarkable in Staph. aureus and Pseudomonas.
3) Stability : The stability of fosfomycin was studied using human serum, urine, rat serum and extracted solution of the kidney. No potency was influenced within 24 hours either at room temperature or in the ice box, but a slight drop of potency was noted after 1 week in the ice box.
4) Concentration in the blood and urine : Cup method study employing Moni-trol serum as standard revealed that administration of 500 mg orally at fasting produced a peak level at 2 hours with average of 2.9μg/ml. In the group given after meal, a peak level of 2.4μg/ml was attained at 4 hours after administration. The peak concentration of 261 μg/ml in the urine obtained at 1 hour after administration in the group given at the fasting state, while in the group after meal, a peak concentration of 287 μg/ml obtained at 4 hours. The urinary recovery rate within 6 hours after administration was 13.3% in the group given at fasting and 17.4% in the group after meal.
5) Concentration in internal organs : Fosfomycin was administered orally at a dose of 20 mg/kg in a group consisting of 3 SD strain rats, and the level was the highest in the kidney followed by serum, lungs, heart, and spleen in order. In the group given at fasting, higher concentrations were obtained than that in the group given after meal. The concentration in the urine of rats was 1, 537 μg/ml at the highest, while the concentration in the bile was slightly below.
6) In vivo metabolism : Metabolism of fosfomycin was studied employing human urine. Bioautogram was prepared by thin layer chromatography using two solvent systems. As a result, fosfomycin was found not to be metabolized in vivo.
7) Clinical results : Fosfomycin was used in the treatment of 23 cases of surgical infections, a good result being obtained in 16 of 20 cases except for 3 cases with unknown result, and a poor in 4 cases. As to side effects, among 23 cases diarrhea was observed in one case and severe rash in another case, leading to discontinuance of the drug. No other particular noteworthy effects were encountered.
