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Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis
Abstract:
Tobramycin, sisomicin, and amikacin were compared with gentamicin in the therapy of experimental E. coli meningitis in rabbits. Meningitis was produced in 40 animals by intracisternal injection of 10(5) E. coli. Three dosages of each antibiotic were administered intravenously over 8 hours. Serum and CSF samples were obtained at 0,2,4,6, and 8 hours for determination of aminoglycoside concentrations and CSF bacteria counts. The four aminoglycosides demonstrated comparable penetration into the CSF. The mean percent penetration (CSF conc./serum conc. X 100%) with the three dosages was 10 to 50% for gentamicin, 8 to 23% for tobramycin, 6 to 16% for sisomicin, and 11 to 23% for amikacin. This variation in penetration reflected individual differences in each dosage group and the increase in percent penetration that was observed during therapy. Sisomicin and gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers decreased 3.07 logs in rabbits treated with sisomicin and 2.44 logs in animals treated with gentamicin. Even through CSF concentrations were comparable, the group treated with tobramycin demonstrated only a 0.64 log decrease and the amikacin group had a 0.45 log increase in mean CSF titers. The bactericidal effect of sisomicin appeared to be more rapid than that of gentamicin. During the first 2 hours of therapy CSF titers declined 1.02 logs in animals treated with sisomicin as compared to 0.37 log in animals receiving gentamicin even though gentamicin concentrations were higher (mean 7.4 vs. 4.1 gm./ml.). Sisomicin also demonstrated greater bactericidal activity than the other aminoglycosides in normal CSF in vitro. The results of this study suggest that sisomicin may be of value in the therapy of E. coli meningitis.
Insights
Sisomicin demonstrated superior bactericidal activity against E. coli meningitis in rabbits compared to gentamicin, tobramycin, and amikacin. This suggests sisomicin
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Bacterial meningitis, particularly E. coli meningitis, remains a significant cause of morbidity and mortality.
- Aminoglycosides are crucial antibiotics for treating Gram-negative bacterial infections, including meningitis.
- Comparative efficacy of different aminoglycosides in experimental meningitis models is essential for guiding clinical treatment.
Purpose of the Study:
- To compare the efficacy of tobramycin, sisomicin, and amikacin against gentamicin in treating experimental E. coli meningitis in rabbits.
- To evaluate the penetration, bactericidal activity, and therapeutic potential of these aminoglycosides in the cerebrospinal fluid (CSF).
Main Methods:
- Experimental E. coli meningitis was induced in 40 rabbits via intracisternal injection.
- Three dosages of gentamicin, tobramycin, sisomicin, and amikacin were administered intravenously over 8 hours.
- Serum and CSF samples were collected serially to determine aminoglycoside concentrations and CSF bacterial counts.
Main Results:
- All four aminoglycosides showed comparable penetration into the CSF, with percentages ranging from 6% to 50% depending on the drug and dosage.
- Sisomicin and gentamicin exhibited significant in vivo bactericidal activity, reducing CSF bacterial titers by 3.07 and 2.44 logs, respectively.
- Tobramycin and amikacin showed limited efficacy, with bacterial titers decreasing by 0.64 logs and increasing by 0.45 logs, respectively.
Conclusions:
- Sisomicin demonstrated rapid and potent bactericidal activity in CSF, surpassing gentamicin, tobramycin, and amikacin in experimental E. coli meningitis.
- Despite comparable CSF penetration, tobramycin and amikacin were less effective in reducing bacterial loads.
- Sisomicin shows promise as a valuable therapeutic agent for E. coli meningitis.