Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare

Onyeji, C.O.; Nightingale, C.H.; Tessier, P.R.; Nicolau, D.P.; Bow, L.M.

Journal of Infectious Diseases 172(3): 810-816


ISSN/ISBN: 0022-1899
PMID: 7658075
DOI: 10.1093/infdis/172.3.810
Accession: 008103446

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The effects of ofloxacin, clarithromycin, and azithromycin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) against Mycobacterium avium-Mycobacterium intracellulare (MAI) were evaluated in an in vitro human macrophage infection model. Treatment of MAI-infected macrophages with GM-CSF alone induced a maximal killing effect at 1000 U/mL, and the potency was increased 100-fold by encapsulating the cytokine within liposomes. Antibiotics were applied at concentrations close to their clinically achievable serum trough and peak levels. Addition of GM-CSF to azithromycin and therapeutic trough concentrations of ofloxacin and clarithromycin was associated with significant (P < .01) augmentation of antimycobacterial activity compared with the effects of the agents alone. However, the enhancement effect by GM-CSF was not seen with therapeutic peak concentrations of ofloxacin and clarithromycin. Thus, GM-CSF may be a useful adjunct in the treatment of MAI infections with azithromycin, clarithromycin, and ofloxacin.