In vitro studies of investigational beta-lactams as possible therapy for Pseudomonas aeruginosa endocarditis
Abstract:
The inadequacy of the present medical therapy of Pseudomonas aeruginosa endocarditis prompted an investigation of the in vitro activities of aztreonam, cefsulodin, and imipenem compared with that of ticarcillin against 37 strains of P. aeruginosa isolated from patients with endocarditis. Inhibitory and bactericidal activities were studied for each beta-lactam alone and in combination with tobramycin. All agents showed excellent inhibitory activity. Imipenem was the most inhibitory beta-lactam yet lacked inhibitory synergy against 95% of the strains and bactericidal synergy against 62%. Tolerance to imipenem was seen in six strains. Aztreonam alone was bactericidal against 46% of the strains (at 16 micrograms/ml) and showed bactericidal synergy in 70%. Cefsulodin alone was even less active but similar to aztreonam synergistically. Ticarcillin and tobramycin inhibited all strains as single agents and showed universal bactericidal synergy in combination. None of the new beta-lactams showed consistent superiority to the presently used agent, ticarcillin.
Insights
New antibiotics like imipenem show limited synergy against Pseudomonas aeruginosa endocarditis strains. Ticarcillin combined with tobramycin remains a reliable treatment option for this serious infection.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Pseudomonas aeruginosa endocarditis presents significant treatment challenges.
- Current medical therapies for P. aeruginosa endocarditis are often inadequate.
Purpose of the Study:
- To evaluate the in vitro activity of aztreonam, cefsulodin, and imipenem against P. aeruginosa strains from endocarditis patients.
- To compare these novel beta-lactams with ticarcillin, both alone and in combination with tobramycin.
Main Methods:
- In vitro susceptibility testing (inhibitory and bactericidal) was performed.
- Thirty-seven P. aeruginosa strains isolated from endocarditis patients were analyzed.
- Beta-lactam agents were tested alone and in combination with tobramycin.
Main Results:
- All tested beta-lactams demonstrated excellent inhibitory activity against P. aeruginosa.
- Imipenem exhibited the highest inhibitory activity but lacked significant synergy.
- Ticarcillin and tobramycin showed universal bactericidal synergy, outperforming new beta-lactams.
Conclusions:
- Novel beta-lactams (aztreonam, cefsulodin, imipenem) did not consistently outperform ticarcillin.
- Combination therapy with ticarcillin and tobramycin remains a highly effective strategy.
- Further research into synergistic combinations for P. aeruginosa endocarditis is warranted.
