In-vitro and in- vivo efficacy of ceftriaxone, moxalactam, and chloramphenicol against haemophilus influenzae type b

Thirty strains (10 ampicillin-resistant) of Haemophilus influenzae type b demonstrated in-vitro mean MICs of 0·32 mg/l of chloramphenicol, 0·03 mg/l of moxalactam, and 0·004 mg/l of ceftriaxone. Six strains of H. influenzae type b (four ampicillin-resistant) were used to produce bacteraemia and meningitis in infant rats which were then treated with these antibiotics. Antibiotic dosages were selected to achieve peak blood levels at least 3×4 times the MIC and to achieve comparable peak moxalactam and ceftriaxone blood levels. Twenty-six animals received chloramphenicol (10 mg/kg/dose every 6 h × 4 doses), with peak blood level of 1·22 mg/l. Fifty-eight rats received ceftriaxone (0·1 mg/kg/dose every 8 h × 3 doses) with peak blood level of 0·47 mg/l, while 51 animals received moxalactam (0· mg/kg/dose every 8 h × 3 doses) with peak blood level of 0·45 mg/I. When cultured 32 h after initiation of treatment, no blood or CSF was sterile from the animals treated with chloramphenicol; only 6/51 animals treated with moxalactam had negative blood cultures and 7/51 had negative CSF cultures at that time. Forty-two per cent of those with positive cultures showed 2 to 3 log decrease in cfu/ml. In contrast, 55/58 animals treated with ceftriaxone had sterile blood and CSF (P<0·001). These results indicate that ceftriaxone is much more effective than moxalactam or chloramphenicol in the treatment of H. influenzae type b sepsis and meningitis in this animal model.