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Related Experiment Videos

A54145 a new lipopeptide antibiotic complex: microbiological evaluation.

F T Counter1, N E Allen, D S Fukuda

  • 1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.

The Journal of Antibiotics
|June 1, 1990
PubMed
Summary

The A54145 antibiotic complex shows in vitro activity against Gram-positive bacteria and Clostridium perfringens. Calcium enhances its antibacterial effects, and resistance is reversible, with Factor A and B demonstrating efficacy in mouse infection models.

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Area of Science:

  • Microbiology
  • Pharmacology

Background:

  • The A54145 complex comprises eight active factors: A, A1, B, B1, C, D, E, and F.
  • Antibiotic resistance is a growing global health concern, necessitating the development of novel therapeutic agents.

Purpose of the Study:

  • To evaluate the in vitro and in vivo antibacterial activity of the A54145 complex and its components.
  • To investigate the role of calcium in the activity of A54145.
  • To assess the development and reversibility of resistance to A54145.

Main Methods:

  • Minimum inhibitory concentrations (MICs) were determined for various Gram-positive organisms.
  • Activity against Clostridium perfringens was tested.
  • Calcium dependence studies were performed.
  • Resistance development and reversibility were assessed using serial passages.

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  • In vivo efficacy was evaluated in mouse infection models.
  • Acute mouse toxicities were determined.

    • Main Results:

    • The A54145 complex exhibited activity against Gram-positive aerobes (MICs 0.25–>32 µg/ml) and Clostridium perfringens.
    • Antibacterial activity was significantly enhanced by calcium (50 mg/liter).
    • Reversible resistance was observed in Staphylococcus and Streptococcus species upon exposure to sublethal concentrations.
    • Factor A showed efficacy against Staphylococcus aureus and Streptococcus pyogenes infections in mice.
    • Factor B demonstrated higher activity against Streptococcus pyogenes in vivo.

    Conclusions:

    • The A54145 complex possesses broad-spectrum activity against Gram-positive bacteria, including Clostridium perfringens.
    • Calcium is crucial for optimizing the in vitro antibacterial efficacy of A54145.
    • The observed resistance to A54145 is readily reversible, suggesting a potential therapeutic advantage.
    • Factors A and B show promise for treating specific Gram-positive bacterial infections in vivo.