Activities of poloxamer CRL-1072 against Mycobacterium avium in macrophage culture and in mice

Chinnaswamy Jagannath, Martin R. Emanuele, Robert L. Hunter

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2898-2903
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume43
Issue number12
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Activities of poloxamer CRL-1072 against Mycobacterium avium in macrophage culture and in mice'. Together they form a unique fingerprint.

Cite this