Experimental and clinical studies were made on amikacin, a new aminoglycoside antibiotic derived from kanamycin A on the basis of the mechanism of kanamycin resistance. The results obtained were as follows.
1. Antibacterial activity
The antibacterial activity of amikacin was determined against 50 clinical isolates each of Staphylococcus aureus, Escherichia coli, Klebsiella and Pseudomonas aeruginosa.
Out of them, 39 isolates of Staphylococcus aureus (78%), 43 isolates each of Escherichia coli and Klebsiella (86% each) and 40 isolates of Pseudomonas aeruginosa (80%) were inhibited by amikacin at a concentration of 6.25 μg/ml or less. By means of the standard 2-fold dilution technique, however, amikacin was approximately 2^-1-2^-4 times as active as gentamicin and dideoxykanamycin B.
2. Absorption, excretion and tissue concentration
The peak serum concentration of amikacin in healthy adults occurred after one hour of intramuscular injection in either case of 50 mg/kg dose and 100 mg/kg dose, the values being 2.75-3.50μg/ml and 5.05μg/ml, respectively. The serum concentrations then decreased, showing the serum half-life of 1.4-1.7 hours. The urinary recovery of amikacin within 6 hours of intramuscular injection ranged from 50-60 %.
The peak serum concentrations of amikacin in patients with renal insufficiency were higher than those of healthy adults, and marked prolongation of their serum concentration was observed.
The highest tissue concentration of amikacin by a single intramuscular injection to rats at a dose of 10 mg/kg was found in the kidney, following by the serum and lungs. Little distribution to the liver was observed.
3. Clinical results
Four cases with urinary tract infection and one case with pyothorax, totalling 5 cases, were treated with amikacin. Response was excellent or good in 3 cases with urinary tract infection, but its application was stopped due to exanthema in the case with pyothorax. No other side-effects were observed.