Abstract
A new aminoglycoside antibiotic, lividomycin, was studied bacteriologically and clinically.
1) In a study by the agar plate dilution method on 111 strains of 18 species, Staphylococci were found to be very sensitive with the MICs of 3.12 μg/ml or less. Corynebacterium diphtheriae, Hemophilus influenzae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella, Shigella and Salmonella were fairly sensitive showing the MICs of less than 12.5μg/ml. Pseudomonas aeruginosa and Proteus-Providence were mederately sensitive to the agent with the MICs of 12.5μg/ml more or less.Diplococcus pneumoniae, β-Hemolytic streptococci, α-Hemolytic streptococci and Enterococci, however, were found to be poorly sensitive to the agent, showing the MICs of more than 50μg/ml.
2) By the thin-layer cylinder-plate technique using Bacillus subtilis PCI 219 as a test organism, lividomycin was found to be assayable to the lower limit of 0.62μg/ml in serum (1: 2 in pH 7.8 phosphate buffer).
Following a single intramuscular administration of 1,000mg, peak serum levels of 20-30μg/ml were obtained at 1 or 2 hours, with persistence of more than 0, 8μg/ml over ensuing 12 hours.And the agent was recovered from urine for the most part in the microbiologically active form, showing the urinary recovery of 56-61% after 18 hours.
3) With the view of preparing grounds for application of the single-disc method to the sensitivity test in the clinical laboratory, statistical analysis of the dose-response data concerning the interrelations between MIC value and diameter of inhibition zone were conducted on each of i) conventional (overnight: approximately 16 hours) assay, ii) 4-hour rapid assay with heavy inoculum, iii) 6-hour rapid assay with heavy inoculum, iv) delayed (approximately 24 hours) assay for slowly growing bacteria.As the results, e.g.simple regression equation for conventional assay was D (diameter of inhibition zone) =26.9-9.1 log MIC.
Experimental errors of the single-disc method inherent were also obtained in comparison with the ones in the 2-fold dilution method.As the results, range of deviation of assayed MIC expressed in terms of rejection limit (α=0.05) was, e.g.3.0-0.33 for conventional method and 2.1-0.48 for dilution method, respectively.
4) Treatment with lividomycin was effective in a case of urinary tract infection caused by E.coil whose sensitivity to lividomycin was determined to be very sensitive by the above mentioned singledisc technique.
