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Pulsed-exposure and postantibiotic leukocyte enhancement effects of amikacin, clarithromycin, clofazimine, and rifampin against intracellular Mycobacterium avium. 1998

L Horgen, and A Jerome, and N Rastogi
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière, BP 484, 97165 Pointe-à-Pitre, Guadeloupe.

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.

UI MeSH Term Description Entries
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009162 Mycobacterium avium A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D002991 Clofazimine A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619) B-663,G-30,320,Lamprene,N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-((1-methylethyl)imino)-2-phenazinamine,B 663,B663,G 30,320,G30,320
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000583 Amikacin A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics. A.M.K,Amikacin Sulfate,Amikacina Medical,Amikacina Normon,Amikafur,Amikalem,Amikason's,Amikayect,Amikin,Amiklin,Amukin,BB-K 8,BB-K8,Biclin,Biklin,Gamikal,Kanbine,Oprad,Yectamid,BB K 8,BB K8,BBK 8,BBK8,Medical, Amikacina,Normon, Amikacina,Sulfate, Amikacin
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D012293 Rifampin A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160) Rifampicin,Benemycin,Rifadin,Rimactan,Rimactane,Tubocin
D017291 Clarithromycin A semisynthetic macrolide antibiotic derived from ERYTHROMYCIN that is active against a variety of microorganisms. It can inhibit PROTEIN SYNTHESIS in BACTERIA by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. 6-O-Methylerythromycin,A-56268,Biaxin,TE-031,A 56268,A56268,TE 031,TE031

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