Therapeutic efficacy of chloramphenicol, co-trimoxazole (trimethoprim/sulphamethoxazole) , cefmenoxime and ceftriaxone in experimental bacteraemia and meningitis caused by ampicillin-resistant Haemophilus influenzae type b
Journal of Antimicrobial ChemoTherapy 22(5): 697-706
ISSN/ISBN: 0305-7453 PMID: 3264831 DOI: 10.1093/jac/22.5.697
Therapeutic efficacy of two newer cephalosporins, cefmenoxime and ceftriaxone, was evaluated in newborn rats with experimental bacteraemia and meningitis due to an ampicillin-resistant strain of Haemophilus influenzae type b, and the results were compared with those of ampicillin, chloramphenicol and co-trimoxazole (trimethoprim/sulphamethoxazole). Measured by MICs and MBCs, cefmenoxime and ceftriaxone were at least a hundred-fold more active in vitro than chloramphenicol. Co-trimoxazole was bacteriostatic in vitro. For in-vivo studies, the following daily doses were used: 200 mg/kg for ampicillin; 100 mg/kg and 200 mg/kg for chloramphenicol; 10/50 mg/kg, 20/100 mg/kg and 100/500 mg/kg for trimethoprim/sulphamethoxazole; 10 mg/kg and 50 mg/kg for cefmenoxime; and 10 mg/kg and 25 mg/kg for ceftriaxone. Cefmenoxime and ceftriaxone were highly efficacious, even at a dose of 10 mg/kg/day, in eradicating the organism from blood and CSF, preventing bacteriological relapse and improving the survival rate. In contrast, chloramphenicol was effective in reducing mortality, but failed to eradicate the organism or to prevent relapse, while co-trimoxazole was least effective in that all but one survivors suffered relapse with positive blood and CSF cultures. Ampicillin gave unexpected results in that the organism was eradicated in all survivors and bacteriological relapse was prevented in most animals (73-75%).