Experimental Pneumonia Due to Haemophilus influenzae: Observations on Pathogenesis and Teatment

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Abstract
A model of pneumonia due to Haemophilus influenzae type b was developed in mice and used for exploration of the pathophysiology of the infection and evaluation of the efficacy of five antimicrobial agents. Adult C57BL/6 mice were challenged with 3 × 109 cfu of H influenzae by intratracheal inoculation. Mice given placebo or no treatment experienced a uniformly bacteremic and fatal infection. Animals given ampicillin, cefamandole, chloramphenicol, erythromycin plus sulfisoxazole, or fludalanine plus pentizidone (MK 0641/MK 0642, an investigational combination drug) survived at a higher rate than did controls (P < .001 at 72 hr for each antibiotic). However, survival rates for the various antibiotic-treated groups were similar. Viable organisms were eradicated from the lungs of antibiotic-treated mice more quickly than from the lungs of controls (P < .001 at 24 hr for each drug). Studies of pulmonary clearance revealed significant differences among regimens; the order of efficacy (from most to least) was ampicillin, chloramphenicol, erythromycin/sulfisoxazole, cefamandole, and fludalanine/pentizidone. This model represents an appropriate system for evaluation of invasive pulmonary infection caused by H influenzae type b. Of the antibiotics assessed, ampicillin was most active in vivo.