Activities of Poloxamer CRL-1072 against Mycobacterium avium in Macrophage Culture and in Mice
AUTOR(ES)
Jagannath, Chinnaswamy
FONTE
American Society for Microbiology
RESUMO
Earlier studies reported that certain large hydrophobic poloxamer surfactants were able to inhibit the growth of Mycobacterium avium-M. intracellulare complex (MAI) in broth and to produce synergistic enhancement of the activity of rifampin. CRL-1072 was synthesized to have an optimal structure for antimicrobic effects and greater purity. Its MIC for MAI in broth was greater than 100 μg/ml. Surprisingly, its MIC for MAI growing in human U937 monocytoid cells was much lower, 5 μg/ml. A still lower concentration, 0.1 μg/ml, produced synergistic enhancement of the activities of clarithromycin, rifampin, amikacin, streptomycin, and clindamycin, but not isoniazid, against MAI infecting monocytoid cells. Mice tolerated injection of doses of CRL-1072 as high as 125 mg/kg of body weight. Pharmacokinetic analysis revealed that the copolymer had an elimination half-life of 60 h and suggested dosing regimens that might produce therapeutic concentrations in tissue. In a mouse model of acute MAI infection, CRL-1072 significantly enhanced the bactericidal activities of clarithromycin and rifampin when it was administered at 1.0 mg/kg intravenously (i.v.) three times per week. CRL-1072 given i.v. or orally also enhanced the bactericidal activity of clindamycin against MAI.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89584Documentos Relacionados
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