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Published on: March 17, 2014
Effect of vincristine sulfate on Pseudomonas infections in monkeys
Abstract:
In rhesus monkeys, intravenous challenge with 0.6 x 10(10) to 2.2 x 10(10)Pseudomonas aeruginosa organisms caused acute illness of 4 to 5 days' duration with spontaneous recovery in 13 of 15 monkeys; blood cultures became negative 3 to 17 days after challenge. Leukocytosis was observed in all monkeys. Intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate was followed by leukopenia in 4 to 5 days. Intravenous inoculation of 4.2 x 10(10) to 7.8 x 10(10) pyocin type 6 Pseudomonas organisms in monkeys given vincristine sulfate 4 days previously resulted in fatal infection in 11 of 14 monkeys, whereas none of four receiving Pseudomonas alone died. These studies suggest that an antimetabolite-induced leukopenia predisposes to severe Pseudomonas sepsis and that such monkeys may serve as a biological model for study of comparative efficacy of antimicrobial agents.
Insights
Vincristine sulfate-induced leukopenia in rhesus monkeys predisposes them to severe Pseudomonas aeruginosa sepsis. This model aids in evaluating antimicrobial agents for treating Pseudomonas infections.
Area of Science:
- Infectious Diseases
- Pharmacology
- Primate Models
Background:
- Pseudomonas aeruginosa infections can be severe, particularly in immunocompromised individuals.
- Leukopenia, a decrease in white blood cell count, is a known risk factor for infection.
- Rhesus monkeys are frequently used as models for human diseases.
Purpose of the Study:
- To investigate the effect of vincristine sulfate-induced leukopenia on the susceptibility of rhesus monkeys to Pseudomonas aeruginosa infection.
- To establish a primate model for studying severe Pseudomonas sepsis and evaluating antimicrobial therapies.
Main Methods:
- Rhesus monkeys were challenged intravenously with Pseudomonas aeruginosa.
- Leukopenia was induced in some monkeys using vincristine sulfate.
- Monkeys were subsequently challenged with Pseudomonas aeruginosa to assess infection severity and mortality.
Main Results:
- Intravenous Pseudomonas aeruginosa challenge caused acute illness with spontaneous recovery in most monkeys.
- Vincristine sulfate administration resulted in significant leukopenia.
- Monkeys with vincristine-induced leukopenia experienced fatal Pseudomonas aeruginosa infections, unlike control groups.
Conclusions:
- Antimetabolite-induced leukopenia significantly increases susceptibility to severe Pseudomonas sepsis.
- This primate model is suitable for comparative studies of antimicrobial agents against Pseudomonas infections.
