Download Orbitomaxillary mucormycosis (zygomycosis) and the surgical

REVIEW
10.1111/j.1469-0691.2009.02989.x
Orbitomaxillary mucormycosis (zygomycosis) and the surgical approach
to treatment: perspectives from a maxillofacial surgeon
A. D. Rapidis
Department of Maxillofacial Surgery, Greek Anticancer Institute, St. Savvas Hospital, Athens, Greece
Abstract
Rhinocerebral or rhino-orbitocerebral (mucormycosis) zygomycosis (ROCZ) usually occurs among patients with poorly controlled
diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload or extensive burns, in patients undergoing treatment with glucocorticosteroid agents, or in patients with neutropenia related to haematologic malignancies. The disease process starts
with inhalation of the fungus into the paranasal sinuses. The fungus may spread to invade the palate, sphenoid sinus, cavernous sinus,
orbits or cranially to invade the brain. Pain and swelling precede oral ulceration and the resulting tissue necrosis can result in palatal
perforation. Infection can sometimes extend from the sinuses into the mouth and produce painful, necrotic ulcerations of the hard
palate. If untreated, infection usually spreads from the ethmoid sinus to the orbit, resulting in the loss of extraocular muscle function
and proptosis. Surgical treatment includes the resection of involved tissues of the face, including skin and muscle, any skin of the nose
that is involved, maxillary and ethmoid sinuses, necrotic tissue of the temporal area and infratemporal fossa, and orbital exenteration.
The keys to successful therapy include suspicion of the diagnosis and early recognition of the signs and symptoms, correction of underlying medical disorders such as ketoacidosis, and aggressive medical and surgical intervention.
Keywords: Maxillectomy, mucormycosis, orbital exenteration, zygomycosis
Clin Microbiol Infect 2009; 15 (Suppl. 5): 98–102
Corresponding author and reprint requests: A. D. Rapidis,
Department of Maxillofacial Surgery, Greek Anticancer Institute, St.
Savvas Hospital, 171 Alexandras Avenue, Athens 115 22, Greece
E-mail: [email protected]
Introduction
Zygomycetes have a wide geographical distribution, are all
thermo-tolerant, and utilize a variety of nutritional substrates. In nature, they are found in the soil, animal faeces
and decaying plant materials [1,2]. They spread by the production of sporangiospores that are released into the environment as airborne propagules. Humans are usually
resistant to the disease because Mucorales fungi are ubiquitous in the environment. Nosocomial infections can occur
from sporangiospores released through contaminated airconditioning systems or contaminated wound dressings. The
fungus exhibits a remarkable affinity for arteries and grows
along the internal elastic lamina, causing thrombosis and
infarction. Infections occur equally in both sexes, irrespective
of age.
Mucormycosis, also known as zygomycosis and phycomycosis, was first described by Paultauf in 1885 [3]. The major-
ity of cases reported have represented either isolated
examples or small, retrospective series. This relative scarcity
of cases hinders the drawing of diagnostic and therapeutic
conclusions [4]. However, with the increasing prevalence of
diabetes and immunosuppressive conditions, mucormycosis
has emerged as an important fungal infection. Based on clinical presentation and the involvement of a particular anatomic
site, mucormycosis can be divided into at least six clinical
categories: (i) rhinocerebral; (ii) pulmonary; (iii) cutaneous;
(iv) gastrointestinal; (v) disseminated, and (iv) miscellaneous
[5,6].
Risk Factors and Pathophysiology of
Rhinocerebral or Rhino-orbitocerebral
Zygomycosis
Rhinocerebral or rhino-orbitocerebral zygomycosis (ROCZ)
usually occurs among patients with poorly controlled diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload or extensive burns, or in patients who
take glucocorticosteroid agents or have neutropenia related
to haematologic malignancies. A recently identified important
clinical feature is the increased susceptibility to mucormycosis of patients with elevated available serum iron. It has been
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Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases
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Rapidis
known for two decades that patients treated with the iron
chelator deferoxamine have a markedly increased incidence
of invasive mucormycosis [7, 8]. However, it is now clear
that iron chelation is not the mechanism by which deferoxamine enables mucormycosis infections. Although deferoxamine is an iron chelator from the perspective of the human
host, Rhizopus spp. actually utilize deferoxamine as a siderophore to supply previously unavailable iron to the fungus.
Patients with diabetic ketoacidosis are at high risk of developing rhinocerebral mucormycosis. Multiple lines of evidence
support the conclusion that patients with systemic acidosis
have elevated levels of available serum iron, probably as a
result of the release of iron from binding proteins in the
presence of acidosis [9]. Neutropenia is another significant
risk factor. The correction of neutropenia with granulocyte
colony-stimulating factor (G-CSF) or granulocyte-macrophage
colony-stimulating factor (GM-CSF) is important to improve
outcome. A breakthrough in the management of zygomycosis
in patients with neutropenia was recently achieved with
empirical voriconazole therapy in the absence of amphotericin B (AmB) [10,11]. Initiation of early and appropriate
antifungal administration and, if required, discontinuation of
steroids or deferoxamine is advisable [12].
Rhinocerebral mucormycosis continues to be the most
common form of the disease, accounting for between onethird and one-half of all cases of mucormycosis. Approximately 70% of rhinocerebral cases (occasionally referred to
as craniofacial cases) occur in diabetes patients with ketoacidosis. More rarely, rhinocerebral mucormycosis has also
occurred in patients who have received a solid organ transplant or those with prolonged neutropenia. Recently, rhinocerebral disease has become an increasing problem in
patients undergoing haematopoietic stem cell transplantation.
These cases have largely been associated with steroid use
for graft vs. host disease [13].
Infection with Zygomycetes can be acquired by inhalation,
ingestion or the deposition of spores in wounds. The fungi
give rise to pathogenic lesions as a result of invasion and
growth within the lumen and walls of major blood vessels,
with ensuing thromboembolism resulting in ischaemia and tissue necrosis. Agents of zygomycosis have a predilection for
the internal elastic lamina of the arterial blood vessels and
spread by angioinvasion. The disease process in the ROCZ
form probably starts with the inhalation of the fungus into
the paranasal sinuses. Upon germination, the fungus may
spread inferiorly to invade the palate, posteriorly to invade
the sphenoid sinus and beyond into the cavernous sinus, laterally to involve the orbits, or cranially to invade the brain.
The fungus has a propensity to grow along the elastic lamina
of the blood vessels, dissecting the lamina away from the
Surgical approaches to orbitomaxillary mucormycosis
99
media. This direct invasion and dissection by the fungus
causes extensive endothelial damage, resulting in thrombus
formation and ischaemia to the surrounding tissues. The
infarcted tissue creates an environment that promotes fungal
proliferation and the resultant poor vascular supply prevents
systemic medical therapy from eradicating the fungus. The
nasal and sinus walls are invaded via these vessels and the
orbit is invaded secondarily via freely communicating foramen and venous channels. The fungus invades the cranium
through either the orbital apex or the cribriform plate of the
ethmoids and ultimately kills its host [14,15].
Clinical Symptoms and Signs
The initial symptoms of ROCZ are consistent with either
sinusitis or periorbital cellulitis and include eye or facial
pain and facial numbness, followed by the onset of conjunctival suffusion, blurry vision and soft tissue swelling. Symptoms that may suggest mucormycosis in susceptible
individuals include multiple cranial nerve palsies, unilateral
periorbital facial pain, orbital inflammation, eyelid oedema,
blepharoptosis, proptosis, acute ocular motility changes,
internal or external ophthalmoplegia, headache or acute
vision loss. Fever is variable and may be absent in up to
half of the cases. White blood cell counts are typically elevated, as long as the patient has functioning bone marrow
[16,17].
Upon visual inspection, infected tissue may appear normal
during the earliest stages of spread of the fungus. Infected
tissue then progresses through an erythematous phase, with
or without oedema, before the onset of a violaceous appearance and, finally, the development of a black, necrotic eschar
as the blood vessels become thrombosed and tissue infarction occurs. Palatal involvement is usually the result of the
direct extension of disease from the maxillary sinus and in
the distribution of the sphenopalatine and greater palatine
arteries. Pain and swelling precede oral ulceration, and the
resulting tissue necrosis can result in palatal perforation.
Infection can sometimes extend from the sinuses into the
mouth and produce painful, necrotic ulcerations of the hard
palate. If untreated, infection usually spreads from the ethmoid sinus to the orbit, resulting in loss of extraocular muscle function and proptosis. Marked chemosis may also be
seen. The infection may rapidly extend into the neighbouring
tissues [18].
Cranial nerve findings represent extensive infection and
signal a grave prognosis. Progressive vision loss, and ultimately blindness, may result from involvement of the optic
nerve, from arterial invasion resulting in infarction, or from
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Clinical Microbiology and Infection, Volume 15, Supplement 5, October 2009
cavernous sinus thrombosis. Cranial nerves V and VII may
also be affected, resulting in ipsilateral loss of facial sensation,
ptosis and pupillary dilation. Infection can also spread posteriorly from either the orbit or sinuses to the central
nervous system (CNS). A bloody nasal discharge may be the
first sign that infection has invaded through the turbinates
and into the brain. When there is extensive CNS involvement, the angioinvasive nature of the fungus may result in
cavernous sinus thrombosis and internal carotid artery
encasement and thrombosis, with resulting extensive cerebral infarctions. Occasionally, cerebral vascular invasion may
lead to haematogenous dissemination of the infection, with
or without development of mycotic aneurysms [19].
Radiographic Diagnostic Methodology
Preoperative contrast-enhanced computed tomography (CT)
is useful in defining the extent of the disease. Scans show the
oedematous mucosa, fluid filling the ethmoid sinuses, and
destruction of periorbital tissues and bony margins. Although
sinus CT is the preferred imaging modality, bony destruction
is often seen only late in the course of the disease after softtissue necrosis has already occurred [20].
Magnetic resonance imaging (MRI) is useful in identifying
the intradural and intracranial extent of the disease, cavernous sinus thrombosis, or thrombosis of the cavernous portion of the internal carotid artery. Perineural spread of the
disease can also be demonstrated with contrast-enhanced
MRI scans.
Although evidence of infection of the soft tissues of the
orbit may sometimes be seen by CT scan, MRI is more
sensitive when soft tissue lesions are depicted. However,
patients with early ROCZ may have normal MRI and CT
scans and surgical exploration with biopsy of the areas of
suspected infection should always be performed in high-risk
patients. Given the limitations of imaging studies, diagnosing
mucormycosis almost always requires histopathological evidence of fungal invasion of the tissues [21]. There are no
reliable serologic, polymerase chain reaction (PCR)-based or
skin tests for mucormycosis. Therefore, the diagnosis should
be made by biopsy of infected tissues. The biopsy should
demonstrate the characteristic wide, ribbon-like, aseptate
hyphal elements that branch at right angles. The organisms
are often surrounded by extensive necrotic debris. Other
fungi, including Aspergillus, Fusarium and Scedosporium spp.,
may look similar to the Mucorales on biopsy [22]. However,
these moulds have septae, are usually thinner, and branch at
acute angles. The genus and species of the infecting organism
may be determined by culture of the infected tissue. How-
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ever, the organism is rarely isolated from cultures of blood,
cerebrospinal fluid, sputum, urine, faeces or swabs of
infected areas.
Surgical Treatment and Antifungal Therapy
Aggressive early surgical debridement of the infected craniofacial tissues is the cornerstone of successful treatment of
ROCZ mucormycosis. This includes resection of involved tissues of the face, including skin and muscle, any skin of the
nose that is involved, maxillary and ethmoid sinuses, necrotic
tissue of the temporal area and infratemporal fossa, and orbital exenteration. Orbital exenteration may be life-saving in
the presence of active fungal invasion of the orbit and should
be considered for an actively infected orbit with a blind,
immobile eye. It has been considered helpful even after intracranial spread has occurred. Whether or not to perform
orbital exenteration is the most difficult decision in the surgical management of orbital mucormycosis because the procedure may represent a life-saving measure achieved at the
cost of permanent mutilation [23].
Surgical debridement usually proceeds quickly because of
an almost bloodless field. An aggressive surgical approach
appears to enhance survival. The keys to successful therapy
include suspicion of the diagnosis with early recognition of
the signs and symptoms, correction of underlying medical
disorders such as ketoacidosis, and aggressive medical and
surgical intervention [24]. The use of all available therapeutic
modalities in the treatment of this often fatal infection,
including intravenous liposomal AmB and hyperbaric oxygen
in addition to the aggressive surgical debridement, are mandatory. Treatment with AmB at the highest tolerable dose is
necessary. The use of AmB is limited by frequent side-effects,
the most important of which is its dose-limiting nephrotoxicity. Most of the negative side-effects can be avoided by
using lipid preparations of AmB [25]. This lipid-based formulation increases circulation time and alters the biodistribution
of the associated AmB. Because drugs complexed with lipid
vehicles remain longer in the vasculature, they are able to
localize and reach greater concentrations in tissues with
increased capillary permeability (i.e. tissues in which infection
and inflammation are present) compared with regions of
normal tissue, which are essentially impermeable to lipidcomplexed drugs [26]. This method of increasing the localization of drugs to diseased sites is referred to as ‘passive
targeting’. It enhances delivery of the agent to the fungi,
infected organs and phagocytes with lower toxicity, while
maintaining antifungal efficacy by ensuring significantly higher
sustained tissue levels of the drug. Within these sites, drug
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Rapidis
release occurs through the action of lipases from surrounding inflammatory cells. The lipid formulations may also enable
better solubility into the CNS. The cerebrospinal fluid penetration of conventional AmB is known to be poor and,
although the concentration of lipid-based AmB in brain tissue
remains unknown, studies describe its successful use in cryptococcal meningitis [27, 28]. Furthermore, the lethal dose (LD50)
of lipid-based AmB is approximately 10–15 times higher than
that of conventional AmB and has substantially reduced renal
toxicity. Thus, the lipid formulations are ideally suited for therapy against infections such as ROCZ, which require large
doses of drug given for long periods of time [29]. The recommended dose of liposomal AmB is 5 mg/kg/day prepared as a
1 mg/mL infusion and delivered at a rate of 2.5 mg/kg/h. There
are an increasing number of reports of salvage posaconazole
therapy for refractory mucormycosis [14]. Successful outcomes of posaconazole administered in conjunction with AmB
have been seen in patients with ROCZ mucormycosis and in a
heart-kidney transplant patient who failed on amphotericin
therapy [30]. Currently, novel regimens for the treatment of
mucormycosis include a combination of lipid-based amphotericin plus either an echinocandin or itraconazole or both
[25, 31, 32].
In addition, compassionate-use posaconazole is currently
available, and its potential for combination therapy with a
polyene, caspofungin, or both, is worthy of study. Further
data are needed to determine whether posaconazole, alone
or in combination with AmB, may be useful for the treatment of mucormycosis. Hyperbaric oxygen has been used as
an adjunct to the current therapeutic approach of aggressive
surgical debridement, AmB therapy and control of underlying
predisposing conditions. Although studies have shown that
hyperbaric oxygen exerts a fungistatic effect, its most
important effect is to aid neovascularization with subsequent
healing in poorly perfused acidotic and hypoxic – but viable –
tissue [8]. Hyperbaric oxygen therapy for mucormycosis
should consist of exposure to 100% oxygen for 90 min to
2 h at pressures of 2.0–2.5 atmospheres with one or two
exposures daily for a total of 40 treatments. Reported toxicities of hyperbaric oxygen include teratogenicity and, rarely,
pulmonary or CNS side-effects. Although hyperbaric oxygen
is offered by only a few medical facilities, it may be warranted in patients who appear to be deteriorating despite
maximal surgical and medical therapy [23, 33].
Surgical approaches to orbitomaxillary mucormycosis
101
can occur within several days to a few weeks, even when
appropriate treatment has been instituted. Appropriate management results in a cure in only approximately half of rhinocerebral infections. Given the rapidly progressive nature of
rhinocerebral mucormycosis and the marked increase in
mortality when the fungus penetrates the cranium, any diabetes patient with a headache and visual changes is a candidate
for prompt evaluation which should include imaging studies
and nasal endoscopy to rule out mucormycosis. Published
case series continue to support the need for surgical
debridement to optimize outcomes [34]. For example, in a
case series totalling 49 patients with rhinocerebral mucormycosis, the mortality rate was 70% in cases treated with
antifungal agents alone compared with 14% in cases treated
with antifungal agents plus surgery [35]. Similarly, in a combined series of rhinocerebral, cutaneous and pulmonary
mucormycosis, 11 of 17 (65%) patients treated with surgery
plus antifungal agents survived the infection, compared with
none of seven (0%) patients treated with antifungal agents
alone [36]. The nature of the underlying disease and the
reversibility of the immune dysfunction are also important
determinants of survival. One study showed that 75% of
patients with rhinocerebral disease who had no underlying
immune compromise survived, whereas 60% of those with
diabetes and only 20% of patients with other immunocompromised states were cured.
Conclusions
The overall survival rate of patients with mucormycosis is
approximately 50%, although survival rates of up to 85%
have been reported more recently [27]. Much of the variability in outcome is due to the various forms of the disease.
Rhino-orbitocerebral mucormycosis has a higher survival
rate than does pulmonary or disseminated mucormycosis
because the rhinocerebral disease can frequently be diagnosed earlier and the most common underlying cause, diabetic ketoacidosis, can be treated readily. By contrast,
pulmonary mucormycosis has a high mortality (65% at
1 year) because it is difficult to diagnose and it frequently
occurs in neutropenic patients [11]. Reconstruction should
be delayed to ensure that the patient survives, that the
infection is completely cleared and that the remaining tissue
is healthy [37].
Subsequent Clinical Course and Prognosis
Transparency Declaration
Mucormycosis is the most acutely fatal fungal infection in
humans, with mortality rates of 15–34% [4, 23, 26]. Death
The author declares no conflicts of interest.
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References
1. Ameen M, Arenas R, Martinez-Luna E, Reyes M, Zacarias R. The
emergence of mucormycosis as an important opportunistic fungal
infection: Five cases presenting to a tertiary referral center for
mycology. Int J Dermatol 2007; 46: 380–384.
2. Bhatti Z, Shaukat A, Almyroudis NG, Segal BH. Review of epidemiology, diagnosis, and treatment of invasive mould infections in allogeneic hematopoietic stem cell transplant recipients. Mycopathologia
2006; 162: 1–15.
3. Paultauf A. Mycosis mucorina. Arch Pathol Anat 1885; 102: 543.
4. Spellberg B, Edwards J, Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005; 18: 556–569.
5. Pagano L, Ricci P, Tonso A et al. Mucormycosis in patients with haematological malignancies: A retrospective clinical study of 37 cases.
Gimema infection program (gruppo italiano malattie ematologiche
maligne dell’adulto). Br J Haematol 1997; 99: 331–336.
6. Nosari A, Oreste P, Montillo M et al. Mucormycosis in hematologic
malignancies: An emerging fungal infection. Haematologica 2000; 85:
1068–1071.
7. Islam MN, Cohen DM, Celestina LJ, Ojha J, Claudio R, Bhattacharyya
IB. Rhinocerebral zygomycosis: An increasingly frequent challenge:
Update and favorable outcomes in two cases. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2007; 104: e28–34.
8. Garcia-Covarrubias L, Bartlett R, Barratt DM, Wassermann RJ.
Rhino-orbitocerebral mucormycosis attributable to apophysomyces
elegans in an immunocompetent individual: Case report and review
of the literature. J Trauma 2001; 50: 353–357.
9. Hosseini SM, Borghei P. Rhinocerebral mucormycosis: Pathways of
spread. Eur Arch Otorhinolaryngol 2005; 262: 932–938.
10. Pongas GN, Lewis RE, Samonis G, Kontoyiannis DP Voriconazoleassociated zygomycosis: A significant consequence of evolving antifungal prophylaxis and immunosuppression practices? Clin Microbiol Infect
2009; 15: in press.
11. Rutar T, Cockerham KP. Periorbital zygomycosis (mucormycosis)
treated with posaconazole. Am J Ophthalmol 2006; 142: 187–188.
12. Orguc S, Yuceturk AV, Demir MA, Goktan C. Rhinocerebral mucormycosis: Perineural spread via the trigeminal nerve. J Clin Neurosci
2005; 12: 484–486.
13. Pagano L, Offidani M, Fianchi L et al. Mucormycosis in hematologic
patients. Haematologica 2004; 89: 207–214.
14. Petrikkos G, Skiada A, Sambatakou H et al. Mucormycosis: Ten-year
experience at a tertiary-care center in greece. Eur J Clin Microbiol
Infect Dis 2003; 22: 753–756.
15. Uckay I, Chalandon Y, Sartoretti P et al. Invasive zygomycosis in
transplant recipients. Clin Transplant 2007; 21: 577–582.
16. O’Neill BM, Alessi AS, George EB, Piro J. Disseminated rhinocerebral
mucormycosis: A case report and review of the literature. J Oral
Maxillofac Surg 2006; 64: 326–333.
17. Cheema SA, Amin F. Five cases of rhinocerebral mucormycosis. Br J
Oral Maxillofac Surg 2007; 45: 161–162.
18. Tugsel Z, Sezer B, Akalin T. Facial swelling and palatal ulceration in a
diabetic patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2004; 98: 630–636.
19. Liang KP, Tleyjeh IM, Wilson WR, Roberts GD, Temesgen Z. Rhinoorbitocerebral mucormycosis caused by apophysomyces elegans.
J Clin Microbiol 2006; 44: 892–898.
CMI
20. Franquet T, Gimenez A, Hidalgo A. Imaging of opportunistic fungal
infections in immunocompromised patient. Eur J Radiol 2004; 51:
130–138.
21. Mnif N, Hmaied E, Oueslati S et al. [imaging of rhinocerebral mucormycosis]. J Radiol 2005; 86: 1017–1020.
22. Ghadiali MT, Deckard NA, Farooq U, Astor F, Robinson P, Casiano
RR. Frozen-section biopsy analysis for acute invasive fungal rhinosinusitis. Otolaryngol Head Neck Surg 2007; 136: 714–719.
23. Greenberg RN, Scott LJ, Vaughn HH, Ribes JA. Zygomycosis (mucormycosis): Emerging clinical importance and new treatments. Curr Opin
Infect Dis 2004; 17: 517–525.
24. Bengel D, Susa M, Schreiber H, Ludolph AC, Tumani H. Early diagnosis of rhinocerebral mucormycosis by cerebrospinal fluid analysis and
determination of 16s rrna gene sequence. Eur J Neurol 2007; 14:
1067–1070.
25. Spellberg B, Fu Y, Edwards JE, Jr., Ibrahim AS. Combination therapy
with amphotericin b lipid complex and caspofungin acetate of disseminated zygomycosis in diabetic ketoacidotic mice. Antimicrob Agents
Chemother 2005; 49: 830–832.
26. Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis
2005; 41: 634–653.
27. Sims CR, Ostrosky-Zeichner L. Contemporary treatment and outcomes of zygomycosis in a non-oncologic tertiary care center. Arch
Med Res 2007; 38: 90–93.
28. Richardson M. Ambisome: Adds to the body of knowledge and familiarity of use. Acta Biomed 2006; 77 (Suppl 4): 3–11.
29. Schutz P, Behbehani JH, Khan ZU et al. Fatal rhino-orbito-cerebral
zygomycosis caused by apophysomyces elegans in a healthy patient.
J Oral Maxillofac Surg 2006; 64: 1795–1802.
30. Barchiesi F, Spreghini E, Santinelli A et al. Posaconazole prophylaxis in
experimental systemic zygomycosis. Antimicrob Agents Chemother
2007; 51: 73–77.
31. Vazquez L, Mateos JJ, Sanz-Rodriguez C, Perez E, Caballero D, San
Miguel JF. Successful treatment of rhinocerebral zygomycosis with a
combination of caspofungin and liposomal amphotericin b. Haematologica 2005; 90: ECR39.
32. Nivoix Y, Zamfir A, Lutun P et al. Combination of caspofungin and an
azole or an amphotericin b formulation in invasive fungal infections. J
Infect. 2006; 52: 67–74.
33. Fairley C, Sullivan TJ, Bartley P, Allworth T, Lewandowski R. Survival
after rhino-orbital-cerebral mucormycosis in an immunocompetent
patient. Ophthalmology 2000; 107: 555–558.
34. Tidwell J, Higuera S, Hollier LH, Jr. LH, Facial reconstruction after
mucormycosis in an immunocompetent host. Am J Otolaryngol 2005;
26: 333–336.
35. Talmi YP, Goldschmied-Reouven A, Bakon M et al. Rhino-orbital and
rhino-orbito-cerebral mucormycosis. Otolaryngol Head Neck Surg
2002; 127: 22–31.
36. Pelton RW, Peterson EA, Patel BC, Davis K. Successful treatment of
rhino-orbital mucormycosis without exenteration: The use of multiple treatment modalities. Ophthal Plast Reconstr Surg 2001; 17: 62–66.
37. Lari AR, Kanjoor JR, Vulvoda M, Katchy KC, Khan ZU. Orbital
reconstruction following sino-nasal mucormycosis. Br J Plast Surg
2002; 55: 72–75.
ª2009 The Author
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15 (Suppl. 5), 98–102