Evaluation of ceftazidime, ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis

Abstract

In an infant rat model of Haemophilus influenzae, type b meningitis, where treatment was given 24 and 48 h after infection, the dose of ceftazidime required to eradicate the infection from the CSF of half the animals (CD50) ranged from less than 0.15-1.5 mg/kg/dose. The accompanying blood infections were marginally less responsive to therapy with CD50 values ranging from 0.5-3.9 mg/kg/dose. Comparable data for ampicillin were 12.5-40 mg/kg/dose and 20- greater than 200 mg/kg/dose for the CSF and blood infections while those for chloramphenicol were 18- greater than 100 mg/kg/dose and 22- greater than 100 mg/kg/dose for the CSF and blood infections respectively. Investigation of the relative rates of kill in vivo showed that all three drugs rapidly reduced the bacterial numbers to minimal levels. However, whereas ceftazidime completely eradicated the infection, chloramphenicol, and to a lesser extent, ampicillin-treated rats experienced substantial relapsing. Ceftazidime penetrated into the CSF of infected and uninfected rats slightly better than ampicillin--7.3% compared to 4.0% of the corresponding blood levels respectively. These results indicate that ceftazidime is significantly more active in the infant rat model of H. influenzae, type b meningitis than ampicillin or chloramphenicol.