title: Antimicrobial therapy of experimentally induced Legionnaires' disease in guinea pigs.
abstract: A guinea pig model of Legionnaires' disease was produced by intratracheal inoculation of Legionella pneumophila. The bacterial inoculum given reproducibly resulted in a 95% fatality rate in untreated animals. These animals had lung histopathologic and bacteriologic findings almost identical to those found in human Legionnaires' disease. Administration of cefoxitin and gentamicin, which inhibited the infecting strain in low antibiotic concentration in vitro, was no more effective than saline; this occurred despite adequate serum and lung levels of the drugs. Erythromycin, rifampin, doxycycline, and cotrimoxazole significantly reduced fatality rates. The combinations of erythromycin with rifampin and doxycycline with rifampin were not significantly better or worse than use of either drug alone. In animals treated with any regimen containing rifampin, a dramatically higher rate of bacterial killing was observed than that observed in those animals treated with erythromycin or doxycycline alone. Also, animals treated with any regimen containing rifampin had significantly less late lung histologic evidence of pneumonia than did those treated with other agents. No rifampin-induced resistance was found. This animal model reflects prior clinical findings, provides experimental grounds for therapy with drugs other than erythromycin, and suggests that therapy of Legionnaires' disease should probably include rifampin in most cases.
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002440:Cefoxitin / Q000627:therapeutic use; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004917:Erythromycin / Q000008:administration & dosage / Q000627:therapeutic use; D005839:Gentamicins / Q000627:therapeutic use; D006168:Guinea Pigs; D007877:Legionnaires' Disease / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013420:Sulfamethoxazole / Q000627:therapeutic use; D014295:Trimethoprim / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
chemical_list: D000890:Anti-Infective Agents; D004338:Drug Combinations; D005839:Gentamicins; D004917:Erythromycin; D002440:Cefoxitin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole; D004318:Doxycycline; D012293:Rifampin