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Intraperitoneal injections of 250 mg of ampicillin per kg every 6 h for 30 h sterilized the blood and cerebrospinal fluid of infant rats infected with either a beta-lactamase-containing strain of Haemophilus influenzae type b or a strain lacking the enzyme. However, a single injection of 100 mg/kg sterilized the blood and cerebrospinal fluid of significantly fewer of those rats infected with the beta-lactamase-producing strain. The results suggest that resistance of beta-lactamase-containing strains of H. influenzae in vivo may be inoculum dependent, as demonstrated previously in vitro. The infant rat model appears suited for the quantitative delineation of the effect of beta-lactamase on the treatment of H. influenzae bacteremia and meningitis with beta-lactamase antibiotics.
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