Efficacy of SCH27899 in an animal model of Legionnaires' disease using immunocompromised A/J mice

The efficacy of SCH27899, a new everninomicin antibiotic, against replicati ve Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immu nocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (10(5) CFU per mouse). At 24 h postinoculation, mi ce were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary grow th of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of greater than or equal to 30 MPK resulted in greater than or equal to 90% survival of infected mice, which was associated with inhibition of intrapu lmonary growth of L. pneumophila. In subsequent studies, the efficacy of SC H27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administrati on of SCH27899, OFX, or AZI at a dose of greater than or equal to 30 MPK on ce daily for 5 days resulted in greater than or equal to 85% survival of in fected mice and inhibition of intrapulmonary growth of the bacteria. Howeve r, L. pneumophila CFU were recovered in lung homogenates following cessatio n of therapy with all three antibiotics. These studies demonstrate that SCH 27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH278 99, like OFX and AZI, was bacteriostatic.