2006 Volume 54 Issue 1 Pages 39-42
Since Mycobacterium avium complex (MAC) infections are refractory, the development of new drugs with strong anti-MAC activity or therapeutic regimens using ordinary antimycobacterial drugs in combination with immunoadjuncts is urgently desired. In this study, we studied the effects of chitin, chitosan, and oligochitosan, which exhibit immunopotentiating activity, on the antimicrobial activity of clarithromycin (CAM) in combination with rifampicin (RFP) against MAC organisms replicating within murine peritoneal macrophages (MΦS). Murine peptone-induced peritoneal exudate cells were cultured for 3 days with or without chitin, chitosan, or oligochitosan at concentrations of 10 μg/mL to 100μg/mL and washed with 2% FBS-HBSS; the resulting MΦs were then infected with MAC. When MAC-infected cells were cultured in the presence or absence of CAM/RFP at Cmax doses (CAM, 2.3μg/mL; RFP, 6.2μg/mL) for 7 days, CAM/RFP significantly eliminated the intracellular organisms within MΦs. Although chitin, chitosan and oligochitosan alone did not inhibit intramacrophage bacterial growth, chitin and chitosan, but not oligochitosan, potentiated the bactericidal activity of CAM/RFP against intracellular MAC organisms. Next, chitin and chitosan were examined for their effects on the therapeutic activity of CAM/RFP against MAC infection in mice. Chitin and chitosan did not increase the anti-MAC therapeutic activity of CAM/RFP.
