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Cefamandole and ampicillin therapy in experimental Haemophilus influenzae meningitis
Abstract:
Cefamandole and ampicillin were compared in the therapy of experimental Haemophilus influenzae meningitis in rabbits. Three dosages of each drug were administered as a continuous intravenous infusion for 8 hr to 24 infected animals. Samples of serum and cerebrospinal fluid (CSF) were obtained at 0, 4, and 8 hr for determination of antibiotic concentrations and bacterial titers in CSF. Serum levels of cefamandole were higher, but CSF concentrations of both antibiotics were similar. With the 60-mg/kg per hr dose, the mean serum level was 106 +/- 61 mug/ml for cefamandole and 58 +/- 32 mug/ml for ampicillin (P less than 0.05). With this dosage the mean level in CSF was 7.3 +/- 8.4 mug/ml for cefamandole and 9.5 +/- 5.4 mug/ml for ampicillin (P = 0.26). The percentage penetration ([concentration in CSF/concentration in serum] X 100%) was higher for ampicillin (mean, 18.8% +/- 8.9%) than for cefamandole (mean, 5.6% +/- 3.8%) with all dosages tested (P less than 0.001). The rate of bacterial killing in vivo during therapy was similar with both drugs. The efficacy of cefamandole and ampicillin given intramuscularly for five days (250 mg every 8 hr) was examined in 42 rabbits. Twelve of 14 untreated control rabbits died within 24-72 hr of inoculation. In contrast, 11 of 14 rabbits treated with cafamandole and 10 of 14 rabbits treated with ampicillin were cured of their infections. Cefamandole compared favorably with ampicillin in the therapy of experimental H. influenzae meningitis.
Insights
Cefamandole and ampicillin show similar efficacy in treating experimental Haemophilus influenzae meningitis in rabbits, with ampicillin demonstrating better cerebrospinal fluid penetration. Both antibiotics effectively cleared bacteria and cured infections.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Bacterial meningitis remains a significant global health concern.
- Haemophilus influenzae is a primary causative agent of bacterial meningitis, particularly in children.
- Effective antibiotic therapy is crucial for managing H. influenzae meningitis and improving patient outcomes.
Purpose of the Study:
- To compare the efficacy of cefamandole and ampicillin in treating experimental Haemophilus influenzae meningitis in a rabbit model.
- To evaluate the pharmacokinetic profiles, including serum and cerebrospinal fluid (CSF) concentrations, of cefamandole and ampicillin.
- To assess the in vivo bacterial killing rates and overall therapeutic outcomes of both antibiotics.
Main Methods:
- Experimental meningitis was induced in rabbits and treated with cefamandole and ampicillin via continuous intravenous infusion.
- Serum and CSF samples were collected at various time points to determine antibiotic concentrations and bacterial titers.
- Therapeutic efficacy was further assessed by intramuscular administration of antibiotics over five days.
- Control groups received no treatment.
Main Results:
- Both cefamandole and ampicillin demonstrated similar rates of bacterial killing in CSF.
- Ampicillin exhibited significantly higher penetration into the CSF compared to cefamandole across all tested dosages.
- Both antibiotics were effective in curing experimental H. influenzae meningitis, with high cure rates observed in treated groups compared to untreated controls.
Conclusions:
- Cefamandole is a viable therapeutic option for experimental H. influenzae meningitis, showing comparable efficacy to ampicillin.
- Ampicillin's superior CSF penetration suggests potential advantages in certain clinical scenarios.
- Further research may explore optimal dosing strategies and combinations for enhanced treatment outcomes.