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Ciprofloxacin in experimental Pseudomonas aeruginosa meningitis in rabbits
Abstract:
The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 X 10(7) organisms. The drugs were administered intravenously over seven hours, and simultaneously serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18.4 +/- 12.3; mean +/- standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4.1 +/- 1.3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2.5 mg/kg/h) was -0.51 +/- 0.13 (log10 cfu/ml/h). This was similar to the rate of killing (-0.48 +/- 0.2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6.7 +/- 4.6 mg/l, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased (-0.70 +/- 0.1 and -0.89 +/- 0.4 respectively; r = 0.7407; P less than 0.01). The drugs shows promise in the treatment of pseudomonas meningitis.
Insights
Ciprofloxacin shows promise for treating Pseudomonas aeruginosa meningitis, demonstrating effective penetration into cerebrospinal fluid (CSF) and concentration-dependent bacterial killing in an animal model. Its efficacy in vivo suggests potential as a therapeutic option for this serious infection.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Pseudomonas aeruginosa is a significant cause of bacterial meningitis, particularly in vulnerable populations.
- Effective treatment of P. aeruginosa meningitis is challenging due to the bacterium's intrinsic resistance to many antibiotics.
- Cerebrospinal fluid (CSF) penetration and in vivo efficacy are critical factors for successful antibiotic therapy in meningitis.
Purpose of the Study:
- To evaluate the therapeutic potential of ciprofloxacin for Pseudomonas aeruginosa meningitis.
- To determine ciprofloxacin's penetration into the CSF in an infected animal model.
- To assess its concentration-dependent killing characteristics and compare its efficacy against ceftazidime and tobramycin.
Main Methods:
- An animal model of P. aeruginosa meningitis was established in 40 rabbits.
- Intravenous administration of ciprofloxacin, ceftazidime, and tobramycin over seven hours.
- Simultaneous collection of serum and CSF samples to measure drug concentrations and bacterial counts at multiple time points.
Main Results:
- Ciprofloxacin penetration into the CSF was significantly higher (18.4%) in infected rabbits compared to uninfected rabbits (4.1%).
- The rate of bacterial killing by ciprofloxacin at 5 mg/kg/h was comparable to ceftazidime and high-dose tobramycin.
- Increased ciprofloxacin dosages (15 and 30 mg/kg/h) resulted in a dose-dependent increase in the rate of bacterial killing (P < 0.01).
Conclusions:
- Ciprofloxacin exhibits promising penetration into the CSF during P. aeruginosa meningitis.
- The drug demonstrates concentration-dependent killing of P. aeruginosa in vivo.
- Ciprofloxacin represents a potential therapeutic agent for treating Pseudomonas aeruginosa meningitis.