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Ciprofloxacin in experimental aortic valve endocarditis due to Pseudomonas aeruginosa
Abstract:
Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.
Insights
Ciprofloxacin demonstrated superior efficacy in treating Pseudomonas aeruginosa endocarditis in rabbits compared to netilmicin plus azlocillin. This fluoroquinolone effectively reduced bacterial titers, sterilized vegetations, and prevented relapse, offering a promising therapeutic option for this severe infection.
Area of Science:
- Infectious Diseases
- Pharmacology
- Cardiovascular Medicine
Background:
- Left-sided endocarditis caused by Pseudomonas aeruginosa often leads to treatment failure in humans.
- Pseudomonas aeruginosa is a challenging pathogen, particularly in its serum-resistant forms, complicating therapeutic strategies.
Purpose of the Study:
- To evaluate and compare the efficacy of ciprofloxacin versus a combination of netilmicin and azlocillin in a rabbit model of Pseudomonas aeruginosa aortic valve endocarditis.
- To assess the impact of these antibiotic regimens on bacterial load, vegetation sterilization, clinical cure, and relapse rates.
Main Methods:
- A rabbit model of aortic valve endocarditis was established using a serum-resistant strain of P. aeruginosa.
- Seventy-nine infected rabbits were randomized into three groups: no therapy, ciprofloxacin, or netilmicin + azlocillin.
- Bacterial titers in vegetations were quantified, and outcomes including sterilization, cure, and relapse were assessed.
Main Results:
- Ciprofloxacin significantly reduced P. aeruginosa vegetation titers compared to netilmicin + azlocillin at days 6 and 10 (P < 0.001).
- Ciprofloxacin was more effective in sterilizing vegetations (P < 0.005), curing endocarditis (P < 0.001), and preventing relapse (P < 0.005).
- Both regimens equally sterilized renal abscesses, but azlocillin resistance emerged in vivo, unlike ciprofloxacin or netilmicin.
Conclusions:
- Ciprofloxacin is a highly effective treatment for Pseudomonas aeruginosa endocarditis in this rabbit model, outperforming the netilmicin + azlocillin combination.
- The study highlights the potential of ciprofloxacin as a primary therapeutic agent for P. aeruginosa endocarditis, with a lower risk of resistance development.
- While both regimens addressed renal abscesses, the superior performance of ciprofloxacin in cardiac involvement and relapse prevention is clinically significant.