Jr. Boelaert et al., MUCORMYCOSIS DURING DEFEROXAMINE THERAPY IS A SIDEROPHORE-MEDIATED INFECTION - INVITRO AND INVIVO ANIMAL STUDIES, The Journal of clinical investigation, 91(5), 1993, pp. 1979-1986
This study investigates the pathophysiology of mucormycosis caused by
Rhizopus, which has been reported in 46 dialysis patients, while treat
ed with deferoxamine (DFO). This drug aggravates mucormycosis, which w
e experimentally induced in guinea pigs and which lead to a shortened
animal survival (P less-than-or-equal-to 0.01 ). The drug's effect on
Rhizopus is not mediated through the polymorphonuclear cells. Fe.DFO,
the iron chelate of DFO, abolishes the fungistatic effect of serum on
Rhizopus and increases the in vitro growth of the fungus (P less-than-
or-equal-to 0.0001). This effect is present at Fe.DFO concentrations g
reater-than-or-equal-to 0.01 muM, at which fungal uptake of radioiron
from Fe-55.DFO is observed. A 1,000-fold higher concentration of iron
citrate is required to achieve a similar rate of radioiron uptake and
of in vitro growth stimulation as observed with Fe.DFO. These in vitro
effects of Fe.DFO (1 muM) in serum on radioiron uptake and on growth
stimulation are more striking for Rhizopus than for Aspergillus fumiga
tus and are practically absent for Candida albicans. For these three f
ungal species, the rates of radioiron uptake from Fe-55.DFO and of gro
wth stimulation in the presence of Fe.DFO in serum are directly relate
d (r = 0.886). These results underscore the major role of Fe.DFO in th
e pathogenesis of DFO-related mucormycosis. Pharmacokinetic changes in
uremia lead to a prolonged accumulation of Fe.DFO after DFO administr
ation, which helps explain the increased sensitivity of dialysis patie
nts to DFO-related mucormycosis.