title: A54145 a new lipopeptide antibiotic complex: microbiological evaluation.
abstract: A54145 complex is made up of eight factors; A, A1, B, B1, C, D, E, and F which were active in vitro (MIC 0.25 approximately greater than 32 micrograms/ml) against Gram-positive aerobic organisms. The complex, factor B and B1 were found to be active against two strains of Clostridium perfringens. A calcium dependence study on some of the factors showed that their in vitro antibacterial activity was greatly enhanced by the presence of calcium (50 mg/liter) in the media. Resistance build-up was seen when Staphylococcus sp. and Streptococcus sp. were passed seven times in the presence of sublethal concentrations of A54145 antibiotics. This resistance disappeared immediately when the resistant organisms were passed in the absence of the antibiotics. Factor A was very effective against Staphylococcus aureus and Streptococcus pyogenes infections in mice (sc ED50s of 3.3 approximately 2.4 mg/kg x 2, respectively). Factor B was more active against S. pyogenes in vivo (sc ED50, 0.9 mg/kg x 2). Acute mouse toxicities were determined with these antibiotics. Semisynthetic derivatives were evaluated.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
authors.forename: F T
authors.initials: FT
authors.lastname: Counter
authors.forename: N E
authors.initials: NE
authors.lastname: Allen
authors.forename: D S
authors.initials: DS
authors.lastname: Fukuda
authors.forename: J N
authors.initials: JN
authors.lastname: Hobbs
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: P W
authors.initials: PW
authors.lastname: Ensminger
authors.forename: J S
authors.initials: JS
authors.lastname: Mynderse
authors.forename: D A
authors.initials: DA
authors.lastname: Preston
authors.forename: C Y
authors.initials: CY
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D003016:Clostridium perfringens / Q000187:drug effects; D003470:Culture Media; D004352:Drug Resistance, Microbial; D008074:Lipoproteins / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013210:Staphylococcus / Q000187:drug effects*; D013290:Streptococcal Infections / Q000188:drug therapy*; D013291:Streptococcus / Q000187:drug effects*
chemical_list: C065208:A54145; D000900:Anti-Bacterial Agents; D003470:Culture Media; D008074:Lipoproteins; D002118:Calcium