DEFEROXAMINE AUGMENTS GROWTH AND PATHOGENICITY OF RHIZOPUS, WHILE HYDROXYPYRIDINONE CHELATORS HAVE NO EFFECT

Deferoxamine (DFO), when used in dialysis patients, is a well recogniz ed risk factor for the development of mucormycosis caused by Rhizopus. This study compares, both in vivo and in vitro, the effects produced on Rhizopus by DFO and by two chelators of the hydroxypyridinone class , L1 and CP94. Experimental systemic mucormycosis was induced in the g uinea pig by an i.v. injection of two different strains of Rhizopus: R . microsporus and R. arrhizus. Concomitant i.p. administration of DFO for four days shortened animal survival (P < 0.05), whereas concomitan t administration of either L1 or CP94 did not. In vitro radioiron upta ke by R. microsporus was 100-fold higher from the (55)ferric complex o f DFO than of L1 or CP94. In vitro fungal growth was stimulated sevenf old by the ferric complex of DFO (P < 0.0001) but not significantly by the ferric complex of either L1 or CP94. These results indicate that the ferric complex of DFO but not that of L1 or CP94 specifically stim ulates both the iron uptake and the growth of Rhizopus. They suggest t hat the risk of developing mucormycosis should be minimal with L1 or C P94, as opposed to DFO.