Open AccessEvaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia
Author(s) -
Mónica Fonseca-Aten,
Christine M. Salvatore,
Asunción Mejías,
Ana María Ríos,
Susana Chávez-Bueno,
Kathy Katz,
Ana M. Gómez,
George H. McCracken,
R. Doug Hardy
Publication year - 2005
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.49.10.4128-4136.2005
Subject(s) - mycoplasma pneumoniae , pneumonia , microbiology and biotechnology , medicine , mycoplasma pneumonia , virology , biology
Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment ofM. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 107 CFU ofM. pneumoniae . Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 againstM. pneumoniae was <0.005 μg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluidM. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-γ), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1α, monokine induced by IFN-γ, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1β, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murineM. pneumoniae pneumonia.