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Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents

J L Vildé, E Dournon, P Rajagopalan

    Antimicrobial Agents and Chemotherapy
    |November 1, 1986
    PubMed

    Insights

    This study evaluated antimicrobial drugs against Legionella pneumophila inside human macrophages, defining a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). Erythromycin, rifampin, and pefloxacin were very active, showing promise for treating Legionnaires disease.

    Area of Science:

    • Infectious Diseases
    • Microbiology
    • Pharmacology

    Background:

    • Legionella pneumophila is an intracellular pathogen causing Legionnaires disease.
    • Understanding antimicrobial activity within host cells is crucial for effective treatment.
    • Macrophage models provide insights into drug efficacy against intracellular bacteria.

    Purpose of the Study:

    • To assess the activity of various antimicrobial agents against intracellular Legionella pneumophila multiplication.
    • To define a minimal extracellular concentration inhibiting intracellular multiplication (MIEC) for different drugs.
    • To evaluate the synergistic or antagonistic effects of antimicrobial combinations.

    Main Methods:

    • Culturing human monocyte-derived macrophages infected with Legionella pneumophila.
    • Exposing infected macrophages to serial concentrations of different antimicrobial agents.
    • Determining the minimal extracellular concentration inhibiting intracellular multiplication (MIEC) for each agent.
    • Testing combinations of antimicrobial agents for additive or antagonistic effects.

    Main Results:

    • Antimicrobial agents were classified into very active (e.g., erythromycin, rifampin, pefloxacin), active (e.g., sulfamethoxazole-trimethoprim, doxycycline), and ineffective (e.g., cefoxitin) based on MIEC values.
    • Erythromycin-rifampin and pefloxacin-containing combinations demonstrated additive effects without antagonism.
    • Netilmicin's activity was challenging to ascertain due to its extracellular effects.

    Conclusions:

    • Pefloxacin and erythromycin show significant potential for treating Legionnaires disease due to their high activity against intracellular L. pneumophila.
    • Antimicrobial combinations, particularly those including pefloxacin, offer additive benefits and warrant further clinical investigation.
    • The cellular model effectively predicts antimicrobial efficacy in experimental infections and human cases of Legionnaires disease.

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