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Biological activity of Sch 14342, an aminoglycoside antibiotic coproduced in the gentamicin fermentation
Abstract:
Sch 14342 is an aminoglycoside antibiotic coproduced as a minor component in the gentamicin fermentation. Sch 14342 was found to have the same antibacterial spectrum as gentamicin in vitro and in vivo, and was approximately one-third as active in mouse protection tests. Sch 14342 relative to gentamicin was one-third as toxic in acute tests in mice, one-eighth as toxic in renal toxicity tests in dogs, and an estimated one-tenth as toxic in cat ataxia tests. Sch 14342 possesses a significantly improved therapeutic index relative to gentamicin with reference to ataxia potential and renal toxicity.
Insights
Sch 14342, a gentamicin byproduct, shows similar antibacterial activity but reduced toxicity. This aminoglycoside antibiotic offers a better therapeutic index, particularly for ataxia and renal effects.
Area of Science:
- Pharmacology
- Microbiology
- Drug Development
Background:
- Gentamicin is a widely used aminoglycoside antibiotic.
- Sch 14342 is a minor component produced during gentamicin fermentation.
- Understanding the properties of Sch 14342 is important for potential therapeutic applications.
Purpose of the Study:
- To compare the efficacy and toxicity of Sch 14342 with gentamicin.
- To evaluate the therapeutic index of Sch 14342.
- To assess the potential of Sch 14342 as a therapeutic agent.
Main Methods:
- In vitro and in vivo antibacterial spectrum analysis.
- Mouse protection tests to determine relative activity.
- Acute toxicity, renal toxicity, and ataxia tests in animal models.
Main Results:
- Sch 14342 demonstrated an equivalent antibacterial spectrum to gentamicin.
- In vivo, Sch 14342 was approximately one-third as active as gentamicin in mouse protection.
- Sch 14342 exhibited significantly lower toxicity: 1/3 acute, 1/8 renal, and 1/10 ataxia toxicity compared to gentamicin.
Conclusions:
- Sch 14342 possesses a comparable antibacterial profile to gentamicin.
- Sch 14342 offers a substantially improved therapeutic index, especially concerning renal toxicity and ataxia.
- Sch 14342 represents a promising aminoglycoside antibiotic with enhanced safety.