Antimicrobial therapy of experimentally induced Legionnaires' disease in guinea pigs.

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.

Susceptibility of Legionella spp. to mycinamicin I and II and other macrolide antibiotics: effects of media composition and origin of organisms.

Thirty-three strains of Legionella spp., 29 of which were L. pneumophila, were tested for their susceptibilities to erythromycin (EM), rosaramicin, tylosin, mycinamicin I (Sch-27897), and mycinamicin II (Sch-27896). Testing was performed using an agar dilution method with two different types of media: buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate (BCYE alpha) and filter-sterilized yeast extract medium with 0.1% alpha-ketoglutarate (BYE alpha). The minimal inhibitory concentrations (MICs) of the drugs tested relative to the MICs of erythromycin were: rosaramicin, MIC approximately equal to 0.2 EM MIC; tylosin, MIC approximately equal to 2 EM MIC; mycinamicin I, MIC approximately equal to 0.5 EM MIC; and mycinamicin II, MIC approximately equal to EM MIC. Both types of media caused equivalent partial inactivation of the macrolides which was apparently due entirely to pH effect. MICs on BCYE alpha were one to five times more than those observed on BYE alpha; this may be due to poorer growth on BYE alpha.

Growth of Peptococcus and Peptostreptococcus: effect of variations of culture media on efficiency of recovery.

Reference strains and clinical isolates of Peptococcus and Peptostreptococcus spp. were evaluated for their growth response in supplemented thioglycolate-yeast extract media. Supplements used included various combinations of hemin, menadione, sodium bicarbonate, and Tween 80. Parallel studies were done to compare the efficiency of recovery of viable cells grown in thioglycolate-based media and Wilkins-Chalgren broth and agar. In addition, the effects of age of the medium and medium storage on viable cell yields for reference strains were determined. Reference strains grown in freshly prepared thioglycolate-yeast extract medium supplemented with sodium bicarbonate produced a 10-fold greater increase in the number of viable cells recovered after 24 h of incubation than did the same organisms cultivated in Wilkins-Chalgren medium. The efficiency of recovery of organisms when either mid-logarithmic- or mid-stationary-phase cells were used to prepare standardized inocula was similar. The results suggest that thioglycolate-yeast extract medium supplemented with sodium bicarbonate is more productive than Wilkins-Chalgren medium for the cultivation of anaerobic gram-positive cocci and may represent a suitable alternative for antimicrobial susceptibility testing of these organisms.