Updates by Carol A. Kemper, FACP

GM-CSF Potentiates Anti-Mycobacterial Activity

Source: Kedzierska K, et al. J Infect Dis 2000;181:390-394.

Granulocyte-macrophage colo-ny-stimulating factor (GM-CSF) is known to play a significant role in the maturation and activation of granulocytes and macrophages. Kedzierska and colleagues describe an HIV-infected patient with multidrug resistance disseminated Mycobacterium avium complex (MAC) infection who received GM-CSF (200-400 mcg/day) for 40 days without specific antimycobacterial therapy. Peripheral circulating monocytes obtained before treatment with GM-CSF demonstrated impaired phagocytosis in vitro of MAC (probably due to his underlying HIV infection), which was subsequently partially reversed with GM-CSF therapy. Clinical improvement was difficult to demonstrate although Kedzierska et al believe that his level of MAC bacteremia decreased during GM-CSF therapy based on a prolongation in time for blood specimens to yield a positive MAC culture.

Similar results have been reported by Drs. Deresinski and Bermudez with HIV+ patients with disseminated MAC, as well as a non-HIV-infected patient with disseminated M. kansasii (Kemper CA, et al. J Infect Dis 1998;177:914-920; Bermudez LE, et al. Biotherapy 1995;4:3-10). Blood monocytes obtained from four HIV-infected patients with MAC bacteremia treated with azithromycin and GM-CSF for up to six weeks had significantly enhanced activation and intracellular killing of MAC ex vivo compared with patients receiving azithromycin alone. The effect was apparent within seven days of administration of dosages as low as 50-125 mcg/m2. Similar results have also been reported with candidal infection, although it has been difficult to demonstrate a direct clinical benefit in many of these unusual infections. Nevertheless, there are increasing data to suggest that GM-CSF may be a useful adjuvant in patients with fungal and mycobacterial infections poorly responsive or resistant to conventional therapies.