In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside.
The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.
D000583:Amikacin / Q000494:pharmacology; D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D002855:Chromatography, Thin Layer; D003470:Culture Media; D003982:Dibekacin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005839:Gentamicins / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003470:Culture Media; D005839:Gentamicins; D003982:Dibekacin; C020500:sporaricins; C042178:3-de-O-methylsporaricin A sulfate; D000583:Amikacin