[Bactericidal synergy of josamycin and human polynuclear neutrophils in vitro].
Due to their high intracellular uptake, macrolides may interfere with phagocytes antibacterial system. We have studied the interaction of josamycin with bactericidal activity of human neutrophils (PMNs) or whole blood, in vitro. PMNs preincubated with josamycin (100-0.1 mg/l) display an increased phagocytic ability for K. pneumoniae, independently of the concentrations of josamycin; this effect appears to correlate with the recruitment of an additional population of phagocytizing PMNs without alteration of the mean number of PMN-associated bacteria, whatever the experimental conditions (adherent or non adherent PMNs). PMNs bactericidal function is also enhanced in the presence of josamycin in a dose-dependent manner (mean increase 60 to 370% for josamycin 0.1 to 10 mg/l). Bactericidal activity of whole human blood for P. aeruginosa (a strain resistant to the lytic effect of serum) is increased with a mean survival (CFUt min/CFU 0 min) of 24 and 71% at 60 and 120 min respectively, in the presence of josamycin 10 mg/l, and 42 and 128% in the presence of josamycin 1 mg/l, compared to the survival of the control, 68 and 166%. PMNs functions are not altered by josamycin with the exception of an enhancement of the oxidative burst induced by formylmethionyl-leucyl-phenylalanine, a synthetic compound similar to bacterial derivatives. In conclusion, we have shown a synergic interaction between phagocytes and josamycin for the killing of bacteria resistant to this antibiotic (MiC greater than 128 mg/l). This could be due either to an alteration of some PMN membrane receptors or to alterations of bacteria which render them more sensitive to natural bactericidal mechanisms and/or more able to activate these mechanisms.
Labro
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INSERM U.294, Laboratoire d'Immuno-Hématologie, CHU Xavier-Bichat, Paris.
Babin-Chevaye
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D001770:Blood Bactericidal Activity / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000166:cytology / Q000187:drug effects; D007933:Leucomycins / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000187:drug effects
D007933:Leucomycins
Synergie bactéricide de la josamycine et des polynucléaires neutrophiles humains in vitro.