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Acute toxicity of aminoglycoside antibiotics as an aid in detecting botulism
Abstract:
Gentamicin sulfate or neomycin sulfate injected intraperitoneally into 24- to 27-g mice at a dose of 6.2 mg per mouse elicited botulism-like responses in less than 30 min, but a dose of 3.1 mg per mouse had no observable effect. The normally nontoxic 3.1-mg aminoglycoside dose aggravated the illness induced by an earlier injection of Clostridium botulinum type A or B toxin; it was usually lethal in 2 to 20 min if the preexisting illness was moderate to severe and worsened the condition of mice for about 30 min if the preexisting botulism was mild. The aminoglycoside had no effect when given shortly after the botulinum toxin was injected intraperitoneally; the sensitized state followed a latent period. It rapidly produced botulism-like effects when given to mice which had responded to a mixture of botulinum toxin and another mouse toxic agent with an illness that did not include signs of botulism. An unexpected illness devoid of botulism-like effects was encountered during intestinal colonization of mice by C. botulinum. The appearance of botulism-like signs soon after 3.1 mg of gentamicin sulfate was injected supported other suggestions that this illness included botulism that was masked by the effects of a second cause.
Insights
Aminoglycosides like gentamicin sulfate can cause botulism-like symptoms in mice, especially when combined with Clostridium botulinum toxin. A lower dose exacerbated existing botulism, suggesting masked botulism in other illnesses.
Area of Science:
- Microbiology
- Toxicology
- Pharmacology
Background:
- Aminoglycosides, such as gentamicin sulfate and neomycin sulfate, are antibiotics.
- Clostridium botulinum produces potent neurotoxins responsible for botulism.
- The interaction between aminoglycosides and botulinum toxin in vivo is not fully understood.
Purpose of the Study:
- To investigate the effects of aminoglycosides on botulism-like symptoms in mice.
- To determine if aminoglycosides can unmask or exacerbate botulism.
- To explore the potential for masked botulism in complex illnesses.
Main Methods:
- Intraperitoneal injection of varying doses of gentamicin sulfate or neomycin sulfate into mice.
- Administration of Clostridium botulinum type A or B toxin.
- Observation and recording of botulism-like responses and lethality.
Main Results:
- A high dose (6.2 mg/mouse) of aminoglycosides induced botulism-like responses.
- A lower dose (3.1 mg/mouse) aggravated existing botulism, increasing lethality.
- Aminoglycosides administered shortly after botulinum toxin had no effect, indicating a latent period for sensitization.
- Aminoglycosides induced botulism-like effects in mice exposed to a toxin mixture without prior botulism signs.
- Unexpected illness during intestinal C. botulinum colonization, with subsequent botulism signs after aminoglycoside injection, suggested masked botulism.
Conclusions:
- Aminoglycosides can induce or worsen botulism-like symptoms in mice.
- The findings support the hypothesis that botulism can be masked by other conditions.
- This research highlights the importance of considering masked botulism in differential diagnoses.