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Treatment with imipenem of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis
F Martínez1, F Martín-Luengo, A Garcia
1Department of Microbiology, School of Medicine, University of Murcia, Spain.
Abstract:
The efficacy of imipenem alone or in combination with gentamicin for the treatment of experimental endocarditis in rabbits caused by a penicillin resistant strain of Streptococcus sanguis was compared to that of gentamicin and penicillin G. In vitro, both beta-lactams were bactericidal in action and the combination of gentamicin and imipenem was synergistic after 4 h whereas penicillin G and gentamicin showed synergy after 8 h. Antibiotic treatment was started two days after initiating infection and groups of 20 animals were treated for 5 days with imipenem alone or in combination with gentamicin or with gentamicin and penicillin G. Two of 20 rabbits which received no therapy died whereas all other rabbits survived the treatment period. Blood cultures became negative in 19 rabbits on the second day of treatment with imipenem and gentamicin and sterilization of the vegetations was achieved in 12 animals. In contrast, eight animals given the alternative treatments remained bacteraemic and viable organisms were recovered from the vegetations in every case. However, bacterial counts and vegetation weights only differed significantly between treated animals and controls but not between the different treatment groups. Never the less, these data suggest that combined treatment with imipenem and gentamicin might provide an effective regimen for patients with endocarditis caused by penicillin resistant S. sanguis.
Insights
A combination of imipenem and gentamicin effectively treated experimental endocarditis caused by penicillin-resistant Streptococcus sanguis in rabbits, leading to negative blood cultures and vegetation sterilization.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Endocarditis is a serious infection of the heart lining, often caused by bacteria.
- Penicillin-resistant Streptococcus sanguis poses a treatment challenge.
- Experimental models are crucial for evaluating novel antibiotic therapies.
Purpose of the Study:
- To compare the efficacy of imipenem alone or with gentamicin against penicillin-resistant Streptococcus sanguis endocarditis in rabbits.
- To evaluate the synergistic effects of antibiotic combinations in vitro.
- To determine the optimal treatment regimen for this specific experimental model.
Main Methods:
- In vitro susceptibility testing and time-kill assays were performed.
- Experimental endocarditis was induced in rabbits using a penicillin-resistant S. sanguis strain.
- Animals were treated with imipenem, gentamicin, penicillin G, or combinations thereof for five days.
Main Results:
- In vitro, imipenem and gentamicin demonstrated synergistic activity against S. sanguis.
- In vivo, the imipenem-gentamicin combination resulted in negative blood cultures in 19/20 rabbits and vegetation sterilization in 12/20.
- Alternative treatments showed lower efficacy, with persistent bacteremia and viable organisms in vegetations.
Conclusions:
- Combined imipenem and gentamicin therapy shows promise for treating experimental endocarditis caused by penicillin-resistant S. sanguis.
- This combination may offer an effective alternative for patients with difficult-to-treat endocarditis.
- Further clinical investigation is warranted to confirm these findings in human patients.