Experimental pneumonia due to Haemophilus influenzae: observations on pathogenesis and treatment.
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 X 10(9) 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 less than .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 less than .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.
D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D002435:Cefamandole / Q000627:therapeutic use; D002701:Chloramphenicol / Q000627:therapeutic use; D004338:Drug Combinations / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004917:Erythromycin / Q000627:therapeutic use; D005260:Female; D006192:Haemophilus Infections / Q000188:drug therapy* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000254:growth & development; D007555:Isoxazoles / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D013444:Sulfisoxazole / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D007555:Isoxazoles; D002435:Cefamandole; D004917:Erythromycin; D002701:Chloramphenicol; D013444:Sulfisoxazole; D000667:Ampicillin; C041478:MK 0641; C041479:MK 0642; D000409:Alanine