Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellulare.
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.
Onyeji
C O
CO
Department of Pharmacy Research, Office of Research Administration, Hartford Hospital, Connecticut 06102, USA.
Nightingale
C H
CH
Tessier
P R
PR
Nicolau
D P
DP
Bow
L M
LM
D017963:Azithromycin / Q000633:toxicity*; D002478:Cells, Cultured; D017291:Clarithromycin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D008264:Macrophages / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D015242:Ofloxacin / Q000633:toxicity*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D004337:Drug Carriers; D008081:Liposomes; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017963:Azithromycin; D015242:Ofloxacin; D017291:Clarithromycin