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Therapy of experimental Pseudomonas endocarditis with high-dose amikacin and ticarcillin
Abstract:
Right-sided infective endocarditis due to Pseudomonas aeruginosa was induced in 130 rabbits. Animals received either: (1) no therapy (controls); (2) standard-dose amikacin (AMK) (15 mg/kg/day) plus ticarcillin (300 mg/kg/day), or (3) high-dose AMK (20 or 25 mg/kg/day) plus ticarcillin, for 20 days. Animals in each treatment group were evaluated at 10 days after therapy for bacteriologic relapse. Both standard- and high-dose AMK regimens significantly decreased mortality and Pseudomonas aeruginosa vegetation titers versus controls (p less than 0.01, p less than 0.05, respectively). Despite significantly higher serum AMK levels at 25 mg/kg/day, there was no significant difference in mean vegetation titers, percent of vegetations sterilized, or posttherapy bacteriologic relapse in the three treatment groups. AMK at 20 or 25 mg/kg/day (but not at 15 mg/kg/day) significantly reduced the incidence of pulmonary infarction versus untreated controls (p less than 0.01).
Insights
High-dose amikacin (AMK) plus ticarcillin effectively treated Pseudomonas aeruginosa endocarditis in rabbits, reducing mortality and vegetation. However, higher AMK doses did not improve bacterial eradication or prevent relapse, though they reduced pulmonary infarction.
Area of Science:
- Infectious Diseases
- Pharmacology
- Cardiovascular Medicine
Background:
- Infective endocarditis (IE) is a serious infection of the heart lining.
- Pseudomonas aeruginosa is a challenging pathogen in IE, often requiring combination therapy.
- Optimizing antibiotic regimens for IE is crucial to improve patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of standard- versus high-dose amikacin (AMK) combined with ticarcillin in a rabbit model of Pseudomonas aeruginosa IE.
- To assess the impact of different AMK doses on mortality, bacterial burden, and relapse rates.
- To determine if higher AMK doses reduce complications like pulmonary infarction.
Main Methods:
- A rabbit model of right-sided infective endocarditis caused by Pseudomonas aeruginosa was established.
- Animals were randomized to receive no therapy, standard-dose AMK (15 mg/kg/day) plus ticarcillin, or high-dose AMK (20 or 25 mg/kg/day) plus ticarcillin for 20 days.
- Outcomes including mortality, vegetation bacterial titers, sterilization rates, bacteriologic relapse, and pulmonary infarction were assessed post-therapy.
Main Results:
- Both standard- and high-dose AMK regimens significantly reduced mortality and Pseudomonas aeruginosa vegetation titers compared to controls.
- Despite higher serum AMK levels with the 25 mg/kg/day dose, there were no significant differences in vegetation titers, sterilization rates, or relapse among treatment groups.
- High-dose AMK (20 or 25 mg/kg/day) significantly reduced the incidence of pulmonary infarction compared to controls, an effect not seen with the standard dose.
Conclusions:
- Combination therapy with amikacin and ticarcillin is effective in treating Pseudomonas aeruginosa endocarditis in rabbits.
- Increasing amikacin dosage beyond standard levels does not appear to improve bacteriologic cure rates or reduce relapse.
- Higher doses of amikacin may offer a benefit in reducing pulmonary complications associated with Pseudomonas aeruginosa endocarditis.