Pulsed-exposure and postantibiotic leukocyte enhancement effects of amikacin, clarithromycin, clofazimine, and rifampin against intracellular Mycobacterium avium.
We investigated the postantibiotic effects (PAEs) of four agents against Mycobacterium avium in a human macrophage model under two different experimental conditions. For postantibiotic leukocyte enhancement (PALE), bacteria were exposed to antibiotics prior to their phagocytosis, whereas for pulsed exposure (PE), antibiotics were added after phagocytosis. In both cases, the drugs were used at their peak concentrations in serum (Cmax) for 2 h. The results showed two different patterns: one for the drug for which results under PE and PALE test conditions did not significantly differ (amikacin) and one for drugs for which PAE values were significantly higher under PE test conditions (clarithromycin, clofazimine, and rifampin). These data suggest that even a brief exposure of M. avium to peak concentrations of certain drugs in serum may result in prolonged and persistent suppression of bacterial growth inside human macrophages.
Horgen
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L
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière, BP 484, 97165 Pointe-à-Pitre, Guadeloupe.
Jerome
A
A
Rastogi
N
N
D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D002991:Clofazimine / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009162:Mycobacterium avium / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000583:Amikacin; D002991:Clofazimine; D017291:Clarithromycin; D012293:Rifampin