Is Iron The Key In Infection?

LETTER TO EDITOR

Year : 2007 | Volume : 55 | Issue : 4 | Page : 416

Survival in rhinocerebral mucormycosis: Is iron the key?

Pavan Bhargava
Department of Medicine, Christian Medical College and Hospital,
Vellore - 632 004, Tamil Nadu, India

Date of Acceptance 13-Oct-2007

Sir,

I read with great interest, the study by Jayalakshmi et al. ,
regarding factors for survival in rhinocerebral mucormycosis. [1] The
mortality of patients in this series was approximately 50%, despite
optimal surgical and medical management. This is similar to earlier
series from across the globe. In patients with central nervous system
involvement, prolonged neutropenia or disseminated disease, mortality
is 80-100% despite therapy. [2] Because of its unacceptably high
mortality rate, it is desirable to develop new therapeutic strategies
to treat invasive mucormycosis. It is in this setting, that we must
look at iron chelation, as the next possible therapeutic intervention
to improve mortality and morbidity in this disorder.

Iron is required virtually by all microbial pathogens for growth and
virulence. Mucorales have an exceptional iron requirement for growth
and pathogenicity. [2] The potential therapeutic role of iron
chelation therapy for mucormycosis was initially obscured by the
paradoxically increased risk of developing mucormycosis during
treatment with deferoxamine. [3] This is because, while deferoxamine
is an iron chelator from the perspective of the human host, it serves
as a xenosiderophore to Mucorales, which are able to strip the iron
from the chelator through an energy-dependent process. However, other
iron chelators do not act as iron siderophores for Mucorales.
Treatment of Rhizopus -infected mice with the iron chelator
deferiprone markedly improved survival. It was shown in this study
that deferiprone was as effective as liposomal amphotericin B in
reducing fungal burden and improving survival. [4]

In a more recent study involving the oral iron chelator deferasirox,
when administered to diabetic ketoacidotic or neutropenic mice with
mucormycosis, it significantly improved survival and decreased tissue
fungal burden, with an efficacy similar to that of liposomal
amphotericin B. [5] Most importantly, deferasirox synergistically
improved survival and reduced tissue fungal burden when combined with
liposomal amphotericin B.

This data from animal studies suggests the possibility of a role for
iron chelation in the treatment of mucor mycosis, in addition to
standard anti-fungal therapy and surgery. There is a need for trials
of this drug to establish usefulness in humans with this infection.

» References

1. Jayalakshmi SS, Reddy RG, Borgohain R, Subramanyam C, Panigrahi M,
Sundaram C, et al . Predictors of mortality in rhinocerebral mycosis.
Neurol India 2007;55:292-7.
2. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on
mucormycosis: Pathophysiology, presentation and management . Clin
Microbiol Rev 2005 ; 18 : 556-69.
3. Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Centinieaux B,
Verdonck A, et al . Mucormycosis during deferoxamine therapy is a
siderophore-mediated infection. In vitro and in vivo animal studies. J
Clin Invest 1993;91:1979-86.
4. Ibrahim AS, Edwards JE Jr, Fu Y, Spellberg B. Deferiprone iron
chelation as a novel therapy for experimental mucormycosis. J
Antimicrob Chemother 2006;58:1070-3. [PUBMED] [FULLTEXT]
5. Ibrahim AS, Gebermariam T, Fu Y, Lin L, Husseiny MI, French SW, et
al . The iron chelator deferasirox protects mice from mucormycosis
through iron starvation. J Clin Invest 2007;117:2649-57. [PUBMED]
[FULLTEXT]

Correspondence Address:
Pavan Bhargava
Department of Medicine, Christian Medical College and Hospital,
Vellore - 632 004, Tamil Nadu
India


Source of Support: None, Conflict of Interest: None
Bhargava P. Survival in rhinocerebral mucormycosis: Is iron the key?.
Neurol India 2007;55:416

How to cite this URL:
Bhargava P. Survival in rhinocerebral mucormycosis: Is iron the key?.
Neurol India [serial online] 2007 [cited 2008 Jun 29];55:416.
Available from: http://www.neurologyindia.com/text.a...55/4/416/37101

---------------------------------

Clin Microbiol Rev. 2005 Jul;18(3):556-69. Related Articles, Links

Novel perspectives on mucormycosis: pathophysiology, presentation,
and
management.


Spellberg B, Edwards J Jr, Ibrahim A.


Division of Infect. Dis., Harbor-UCLA Medical Center, 1124 West
Carson
St. RB2, Torrance, CA 90502. bspellb...@labiomed.org.


Mucormycosis is a life-threatening fungal infection that occurs in
immunocompromised patients.
These infections are becoming increasingly common, yet survival
remains very poor.
A greater understanding of the pathogenesis of the disease may lead to
future therapies.
For example, it is now clear that iron metabolism plays a central role
in regulating mucormycosis infections and that deferoxamine
predisposes patients to
mucormycosis by inappropriately supplying the fungus with iron. These
findings raise the possibility that iron chelator therapy may be
useful to treat the infection as long as the chelator does not
inappropriately supply the fungus with iron.
Recent data support the concept that high-dose liposomal amphotericin
is the preferred monotherapy for mucormycosis. However, several novel
therapeutic strategies are available.
These options include combination therapy using lipid-based
amphotericin with an echinocandin or with an azole (largely
itraconazole or posaconazole) or with all three.
The underlying principles of therapy for this disease remain rapid
diagnosis, reversal of underlying predisposition, and urgent surgical
debridement.


PMID: 16020690 [PubMed - in process]


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