Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa
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Abstract:
Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.
Insights
Antibiotic efficacy against Pseudomonas aeruginosa varied in mouse models. While in vitro tests showed susceptibility, in vivo results revealed resistance in some strains, impacting treatment effectiveness.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen.
- Antibiotic resistance in P. aeruginosa is a growing concern.
- Mouse protection tests are crucial for evaluating antibiotic efficacy.
Purpose of the Study:
- To compare the in vivo efficacy of four antibiotics against six strains of Pseudomonas aeruginosa.
- To investigate the impact of bacterial inoculum size and dosing frequency on antibiotic effectiveness.
- To assess antibiotic toxicity and therapeutic index in a mouse model.
Main Methods:
- Mouse protection tests were conducted using four antibiotics and six P. aeruginosa strains.
- In vitro susceptibility testing was performed for all antibiotic-strain combinations.
- Bacterial inoculum size and multiple dosing regimens were varied for gentamicin, tobramycin, and polymyxin B.
Main Results:
- In vitro susceptibility did not always correlate with in vivo efficacy.
- Increased bacterial inoculum reduced the effective dose of gentamicin and tobramycin, but not polymyxin B.
- Tobramycin demonstrated the best therapeutic index, while colistimethate was ineffective in vivo. Polymyxin B was potent but highly toxic.
Conclusions:
- Antibiotic effectiveness against P. aeruginosa in vivo can differ significantly from in vitro susceptibility.
- Factors like inoculum size and dosing influence treatment outcomes.
- Tobramycin and Polymyxin B show promise but require careful dosing due to toxicity concerns.