Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents

Abstract

The activity of serial concentrations of different antimicrobial agents on the multiplication of Legionella pneumophila within human monocyte-derived macrophages was studied. The results led to the definition of a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). According to the MIECs, the antimicrobial agents tested were classified in three groups: (i) very active (MIEC < 0.06 ,ug/ml), such as erythromycin, rifampin, and pefloxacin; (ii) active (1 ,ug/ml 2 MIEC 2 0.1 ,ug/ml), such as sulfamethoxazoletrimethoprim or doxycycline; and (fii) ineffective, such as cefoxitin, which was not active within macrophages at as high as 64 ,ug/ml despite a low MIC (0.2 ,Lg/ml) on bacterial charcoal-yeast extract agar. The activity of netilmicin was difficult to assess because of its effect on extraceliular legionellae. Combinations of erythromycin with rifampin and pefloxacin with erythromycin, rifampin, doxycycline, or netilmicin showed an additive effect and no antagonism. These results obtained in a cellular model are in

Effect of quinolones and other antimicrobial agents on cell-associated Legionella pneumophila

“…This could be explained by the fact that gentamicin was present at the time of bacterial inoculation and therefore inhibited phagocytosis (14) or had its effect before phagocytosis occurred. Our results with gentamicin are similar to those of Bacheson et al (1), who have shown that gentamicin effectively kills cell-associated L. pneumophila 2.5 h after bacterial inoculation (28).…”

“…This result may be related to the fact that intracellular ciprofloxacin levels are approximately 2.5 times the extracellular levels (4). Pefloxacin (28) and ofloxacin (25) have also been shown to inhibit intracellular L. pneumophila growth in similar in vitro models.…”

“…The presence of antibiotics has variable effects on growth. Erythromycin (1,7,19,30), rifampin (7,30), ciprofloxacin (7), pefloxacin (28), gentamicin (1,8,30), nalidixic acid (30), tetracycline (30), and chloramphenicol (30) have each inhibited intracellular L. pneumophila growth under a variety of experimental conditions. Beta-lactam antibiotics such as ampicillin (30), cefoxitin (30), cefotaxime (30), and thienamycin (8) have not been shown to inhibit intracellular L. pneumophila multiplication.…”

Legionnaires disease: historical perspective

“…Strains of Legionella species that are naturally resistant to erythromycin in vitro have not been reported, although resistant mutants have been elicited in the laboratory (62). Erythromycin is bactericidal in vitro (64), but several investigators have demonstrated that it is only bacteriostatic in cultured monocytes (140,260). For these reasons and because of the severe phlebitis that accompanies intravenous administration of erythromycin, the search for alternative therapeutic agents has continued.…”

“…Cure Assay of antimicrobial agents in cultured macrophages may be a less costly substitute for whole animal models (140,260), but more experience with this system is needed. It will be difficult to assess the capability of antibiotics that are rapidly bactericidal to extracellular bacteria.…”