Abstract
In vitro and in vivo antimicrobial activities of lividomycin A were investigated. This substance showed a wide range of antimicrobial activity against most of Gram-positive bacteria including Mycobacterium tuberculosis and was also effective against Gram-negative bacteria including Pseudomonas aeruginosa, but was ineffective for streptococci, diplococci and fungi. The in vitro antimicrobial activity of lividomycin A was the greatest in media of pH 7.8. The minimum inhibitory concentration (MIC) was affected by inoculum size, but the addition of serum caused only slight fluctuation of MIC. In vitro development of resistance to lividomycin A in P. aeruginosa and M. tuberculosis was much slower than that to kanamycin, but was comparable in Staphylococcus aureus. In resistant mutants developed in vitro, cross resistance was observed among lividomycin A, kanamycin and gentamicin. In clinical isolates, however, no distinct cross resistance was found among these three antibiotics. Lividomycin A showed a positive protecting effect for the experimental infections in mice with several bacteria such as S. aureus, P. aeruginosa, Klebsiella pneumoniae and Escherichia coli. It was fairly effective for the experimental infection with the kanamycin-resistant strains of E. coli and P. aeruginosa producing the kanamycin-phosphorylating enzyme.
