mycoses Diagnosis,Therapy and Prophylaxis of Fungal Diseases

Supplement article

Mucormycosis in children: a study of 22 cases in a Mexican

hospital

Alexandro Bonifaz,1 Andre
s Tirado-Sa

nchez,1 Luz Caldero

n,1 Rau

l Romero-Cabello,2 Juan Kassack,3
Rosa Mar
ıa Ponce, Carlos Mena, Alberto Stchigel, Josep Cano5 and Josep Guarro5
1 4 5

1
Mycology Department, Dermatology Service, Hospital General de Mexico (HGM), Reus, Spain, 2Infectology Service, HGM, Reus, Spain, 3Hematology
Service, HGM, Reus, Spain, 4Dermatology Service, Hospital Infantil de Mexico (HIM), Reus, Spain and 5Mycology Unit, Medical School and Institut
d’Investigacio0 Sanita‘ria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain

Summary We present a single-centre, retrospective study (1985–2012) of 22 cases of muco-

rmycosis in children. A total of 158 mucormycosis cases were identified, of which
22 (13.96%) were children. The mean age of the children was 10.3 years (range:
6 months–18 years), and 59% of the infections occurred in males. The rhinocerebral
form was the main clinical presentation (77.27%), followed by the primary cutane-
ous and pulmonary patterns. The major underlying predisposing factors were diabe-
tes mellitus in 68.18% of the patients and haematologic diseases in 27.7% of the
patients. The cases were diagnosed by mycological tests, with positive cultures in
95.4% of the patients. Rhizopus arrhizus was the foremost aetiologic agent in 13/22
cases (59.1%). In 21 cultures, the aetiologic agents were identified morphologically
and by molecular identification. In 10 cultures, the internal transcribed spacer
region of the ribosomal DNA was sequenced. Clinical cure and mycological cure
were achieved in 27.3% cases, which were managed with amphotericin B deoxycho-
late and by treatment of the underlying conditions.

Key words: Mucormycosis, zygomycosis, children, rhinocerebral, diabetes mellitus, haematological malignancy.

those with haematological malignancies (HM) including

Introduction
Mucormycosis (formerly zygomycosis), is an invasive
fungal infection caused by opportunistic fungi. The
main aetiologic agents responsible for mucormycosis
were reclassified in the subphylum Mucoromycotina in
the order Mucorales.1–3 The disease is associated with
the presence of underlying conditions, and it is particu-
larly associated with uncontrolled diabetes mellitus (DM)
in developing countries, such as Mexico and India.4,5 In
contrast, in developed countries, mucormycosis is mostly
associated with immunocompromised patients, such as
Correspondence: Dr A. Bonifaz, 148 Dr. Balmis, Doctores, 06720 Mexico
City, Mexico.
Tel./Fax: +52 55 5761 3923.
E-mail: a_bonifaz@yahoo.com.mx
Submitted for publication 6 January 2014
Revised 10 April 2014
Accepted for publication 14 April 2014
neutropenia due to leukaemia, hematopoietic stem cell
transplantation, and solid organ transplantation. Muco-
rmycosis has also been reported in immunocompetent
hosts with skin trauma or burns.2,3,6
Mucormycosis is a cosmopolitan disease. Its aetio-
logical agents are ubiquitous and thermotolerant
organisms that usually grow in soil and decaying mat-
ter, where they act as contaminant fungi in fruits, vege-
tables, bread and seeds. The spores are released in the
air leading to inhalation or direct inoculation of dis-
rupted skin. Mucormycosis is most commonly caused by
the genus Rhizopus, and the disease is less frequently
caused by Lichtheimia (formerly Absidia), Rhizomucor,
Cunninghamella, Syncephalastrum and other fungi.2,7
The most distinctive forms of the disease are acute rhi-
nocerebral and pulmonary mucormycosis, which
involves thrombosis, angioinvasion and tissue infarc-
tions. Less frequently, other forms of the disease can
occur, including primary cutaneous, gastrointestinal,

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Mycoses, 2014, 57 (Suppl. 3), 79–84 doi:10.1111/myc.12233
A. Bonifaz et al.

disseminated and miscellaneous forms (affecting the 22 paediatric patients were selected, representing
bone, heart and kidneys).2,6,8 13.96% of the sum. All of the cases were confirmed
High morbidity and mortality rates are reported in by clinical and mycological means. The demographic,
mucormycosis patients. Recently, there has been an clinical and mycological data are shown in Table 1.
increase in the incidence of the disease, especially in Table 2 displays the predisposing factors and clinical
adult hosts, which is associated with increases in HM patterns. Figure 1 displays the number of cases per
and DM.9 Prasad et al. [10] noted that the number of year, and the total cases concerning children, and
case reports on children is growing, but there is not a
clear trend showing increased incidence in this age
group. Therefore, it is extremely important to report Table 1 Demographic and clinical characteristics of the study
population.
case series, especially from general hospitals to obtain
accurate knowledge of the disease and its burden. Age
Youngest 6 months
Here, we present our experience regarding mucor-
Oldest 18 years
mycosis cases in children using data gathered over Mean age 10.3 years
28 years in a tertiary hospital. Gender
Male 13 (59)
Female 09 (41)
Patients and methods Mean disease duration 15.5 days
Clinical pattern
This was a retrospective, linear and descriptive study. Rhinocerebral 17 (77.27)
Patients were enrolled between January 1985 and Primary cutaneous 04 (18.18)
December 2012 at Hospital General de Mexico, and Pulmonary 01 (4.54)
patients referred from Hospital Infantil de Mexico were Predisposing factors
Diabetes mellitus 15 (68.18)
also included. The study included a total of 22 cases in
Type 1 11 (50)
which mucormycosis was diagnosed by clinical and Type 2 04 (18.18)
mycological examination. Patients older than 18 years Haematological malignancy 06 (27.27)
of age were excluded. For each registered patient, the Acute lymphocytic leukaemia 04 (18.18)
clinical record included demographic data, predisposing Acute myeloid leukaemia 01 (4.54)
Hodgkin disease 01 (4.54)
factors and the results of the mycological examination.
Severe malnutrition (protein-energy) 01 (4.54) [11]
Direct microscopic examination with 10% potassium Mycological data
hydroxide (KOH) was used to confirm broad-based asep- Direct examination (KOH 10%) 22/22 (100)
tate hyphae. Culturing was carried out in Sabouraud Culture 21/22 (95.4)
dextrose agar, Sabouraud dextrose with chlorampheni- Biopsy 08/22 (36.36)
Treatment
col agar and yeast extract agar. Biopsy was performed
Amphotericin B (deoxycholate) Cure 06 (27.3)
in some cases, and the histological study included hae- Death 16 (72.7)
matoxylin and eosin, periodic acid-Schiff and Grocott-
Gomori’s methenamine silver (GMS) staining. Values in parentheses are expressed in percentage.
Morphological identification of species was completed
for positive cultures, and molecular classification was Table 2 Interrelation between the clinical characteristics and
performed for some cultures. Molecular classification predisposing factors.
was performed at the Mycology Unit, Medical School
Clinical pattern Predisposing factor (%)
and Institut d’Investigaci
o Sanit
aria Pere Virgili, Uni-
versitat Rovira i Virgili in Reus, Spain. Final molecular Rhinocerebral (17 cases/77.27%) DM-T1: 11 (50)
identifications were determined after sequencing the DM-T2: 3 (13.63)
internal transcribed spacer (ITS) region of the ribosomal ALL: 1 (4.54)
AML: 1 (4.54)
DNA (rDNA). The ITS region of the nuclear rDNA was
HD: 1 (4.54)
amplified with the primer pair ITS5 and ITS4.7 The Primary cutaneous (4 cases/18.18%) DM-T2: 1 (4.54)
treatments and patient responses were also recorded. ALL: 2 (9.08)
SM: 1 (4.54)
Pulmonary (1 case/4.54%) ALL: 1 (4.54)
Results
DM-T1, diabetes mellitus type 1; DM-T2, diabetes mellitus type
Between January 1985 and December 2012, 158 mu- 2; ALL, acute lymphocytic leukaemia (ALL); AML, acute myeloid
cormycosis cases were documented. Of these cases, the leukaemia; HD, Hodgkin disease; SM, severe malnutrition.

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80 Mycoses, 2014, 57 (Suppl. 3), 79–84

Figure 1 Number of cases per year. Total
cases and cases in paediatric age.
Figure 2 Incidence of mucormycosis in
children.
Fig. 2 shows the incidence of the disease in period of
28 years.
Importantly, two cases initially had primary cutane-
ous mucormycosis. In one case, the disease was associ-
ated with acute lymphocytic leukaemia (ALL), and in
the second, the disease was associated with severe
malnutrition. In both cases, primary cutaneous muco-
rmycosis originated after the nasogastric tube was
inserted and secured with adhesive bandages, and the
disease then progressed to the rhinocerebral type. Both
cases were counted as having primary cutaneous mu-
cormycosis because it was the initial manifestation.
With regard to the mycological data, the 22 cases
showed aseptate, dichotomous hyphae on direct
© 2014 Blackwell Verlag GmbH
Mycoses, 2014, 57 (Suppl. 3), 79–84
Mucormycosis in children
examination. Cultures were developed from 21/22
cases, and the remaining case had a positive direct
examination and biopsy allowing for inclusion in the
study. Due to the patients’ conditions (thrombocytope-
nia, severe neutropenia or critical illness), biopsies
were performed in only 8/22 cases. The results
reported thrombotic processes with multiple tissue
infarctions and fungal structures similar to observed
on direct examination. Better results were achieved
when GMS staining was used.
Table 3 displays the morphological identification of
the 21 positive cultures. Because this was a retrospec-
tive study, only 10/21 strains (47.61%) were identified
by molecular biology and these results are shown in
81
A. Bonifaz et al.

Table 3 Aetiological agents, morphological and
identification.
Morphological identification/
clinical pattern (n = 21) Molecular biology (n = 10)
Rhizopus arrhizus Rhizopus arrhizus (formerly R. oryzae)
(formerly R. oryzae) (6 strains, HGM-Z-01 al 06)
11 cases RC
1 case PC
Lichtheimia corymbifera Lichtheimia corymbifera
3 cases RC (1 strain, HGM-Z-39)
2 cases PC
Rhizomucor sp. Rhizopus arrhizus
2 cases RC (1 strain, No HGM-Z-33)
Mucor sp. Mucor circinelloides
1 case P (1 strain, HGM-Z-09)
Cunninghamella sp Cunninghamella bertholletiae
1 case PC (1 strain, HGM-Z-18)
RC, rhinocerebral; PC, primary cutaneous; P, pulmonary.
the same table. The main isolated agents were Rhizo-
pus arrhizus in 13/22 cases (59.1%) and Lichteimia cor-
ymbifera in 5/22 cases (10.3%). The rest of the
microorganisms were isolated from one case each.
All the patients received amphotericin B deoxycholate
and management for the overlying conditions, with
metabolic regulation and haematological improvement.
A clinical cure and mycological cure were accomplished
in 6/22 cases (27.3%). Of these six cases, four patients
had the primary cutaneous pattern and two patients
had the rhinocerebral pattern.11
Discussion
Mucormycosis in children is a rare disease. Most
reports of mucormycosis are of isolated cases, and
there are few cases series in the literature. HM is the
major underlying disease in these patients.12–18
This study examines the paediatric mucormycosis
cases of a larger cases series at a single centre. Of the
158 confirmed cases of mucormycosis, 14% were chil-
dren. In accordance with previous reports, patients with
ages from 6 months to 18 years were enrolled, and the
mean age was 10.3 years.12,13,16 A slight male predom-
inance was noted during the study; however, the gender
difference was not significant. This male predominance
agrees with previous reports.10,15,16 Some authors have
correlated this tendency to the protective influence of
oestrogens, but this correlation may not be valid in chil-
dren younger than 12 years of age. Similar to reports in
the United States, France and India,2,4,6,9,19 there was
an increase in total number of mucormycosis cases seen
at our hospital. This was driven by adult cases since the
number of cases in children remained constant (Fig. 1).
molecular Over this 28-year time period, 28 paediatric patients
with mucormycosis were identified. The annual inci-
dence was 0.15 cases/10 000 patient-days in 1985 and
persisted in 0.12 cases/10 000 patient-days in 2012
(Fig. 2). The incidence increased mainly in 1992,
1997, 2000, 2006 and 2010. Averaged over the
28 years, the incidence was 0.12/10 000 patient-days.
In the largest review of mucormycosis, Roden et al.
[9] compiled the results of 929 cases. This review
revealed that the rhinocerebral pattern was the most
frequent clinical manifestation, accounting for 39% of
the cases.9 In our study, the rhinocerebral form was
the predominant form accounting for 77.27% of the
cases. The predominance is probably attributable to
the interrelation between this pattern and the presence
of DM. In the cited review, when evaluating only the
fraction of patients with underlying DM, the percent-
age sum of rhinocerebral and sino-orbital cases was
66%,9 which is similar to our results. It should be
noted that 50% of our patients presented type 1 DM,
which was frequently uncontrolled, provoking meta-
bolic acidosis and the release of iron (Fe2+). Ibrahim
et al. [3,20] emphasised the role of high serum iron
levels in the pathogenesis of mucormycosis. Notably,
100% of DM patients (type 1 and 2) were uncon-
trolled, and nearly all had a history of non-adherence
to medical treatment and suffered frequent decompen-
sation or uncontrolled diabetes. The rhinocerebral
form of mucormycosis is the most acute and fatal pat-
tern. Even with appropriate antifungal therapy, the
disease cannot be cured if the metabolic process is not
regulated, leading to death. A link between diabetic
ketoacidosis and mucormycosis has been consistently
reported, constituting the foremost association in some
countries.4,14,21,22 In Mexico, the increase in obesity
and DM rates could be an explanation for the general
rise in incidence of mucormycosis.23
The second predisposing factor in our series was HM,
mainly ALL, which was present in 18% of the cases.
This result correlated with various reports in the litera-
ture.10,13,15,24 HM was associated with the three clini-
cal patterns reported: rhinocerebral, pulmonary and
primary cutaneous. The latter result is remarkable since
primary cutaneous mucormycosis has been reported to
start under adhesive bandages, in venipuncture sites,
and in locations where adhesive bandages are used to
secure nasogastric tubes.25,26 Primary cutaneous mu-
cormycosis has a good prognosis; nonetheless, the use
of adhesive bandages in the nose facilitates dissemina-
tion to the nasal mucosa, and consequently it leads to
the development of the rhinocerebral pattern, which
has a fatal prognosis.27,28

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82 Mycoses, 2014, 57 (Suppl. 3), 79–84

The pulmonary case was related to ALL. It initiated
as a rapidly progressing pneumonia, somewhat similar
to invasive pulmonary aspergillosis. However, the
diagnosis of mucormycosis was supported by mycolog-
ical data and negative serum galactomannans.9,12,29
Regarding the interrelation of the clinical pattern
and predisposing factors, most rhinocerebral cases
were associated with DM. The rhinocerebral cases
were less frequently associated with HM. The cutane-
ous pattern did not show predominance, and the pul-
monary case was associated with ALL.8,12,26
Prolonged use of the prophylactic voriconazole has
been linked with an increased incidence of mucormyco-
sis.30 However, this drug is not available for prophylaxis
in our hospital, so none of the patients were treated
with this azole.
Mycological examination of wet mounts and cultures
generally allow diagnosis in 100% of cases because the
samples are obtained directly from the patients, which
increase the sensitivity. R. arrhizus was the most fre-
quently identified aetiological agent, as in previous
reports,4,7 and it is also the foremost aetiological agent
in adult patients.5,26 Due to the retrospective nature of
this report, only a portion of the strains were identified
by molecular biological approaches. The genera of the
isolated fungi correlate almost entirely; however, the
identity of the isolated strains is not completely certain,
highlighting the importance of molecular identification.
L. corymbifera was the second most frequently detected
agent, and Mucor, Rhizomucor and Cunninghamella were
commonly detected strains. These strains are easily
recognised because of their morphological features. In
this study, no correlation was found between the clini-
cal form and the aetiological agent. Alvarez et al. [7]
described that individuals with expertise in fungal iden-
tification can provide a high level of accuracy in catego-
rising isolated fungi; however, ITS sequencing should be
mandatory to classify clinically significant species of
zygomycetes and to delineate undescribed species.
Although this study did not intend to report the
diversity of treatments, the cure rate was 27.3%. Cure
was achieved predominantly in primary cutaneous
and initial rhinocerebral cases, and this rate was lower
than the cure rates reported in the literature.2,8,9 We
consider this difference to be due to two factors. Most
cases were associated with uncontrolled diabetes and
arrived at the hospital in the advanced stages of the dis-
ease, which lowers the cure rate. Surgical debridement
contributes to better results, but it was not performed
because of the insufficient length of time. Success in mu-
cormycosis therapy is directly associated with early rec-
ognition and improvement of the underlying conditions
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Mycoses, 2014, 57 (Suppl. 3), 79–84
Mucormycosis in children
(e.g. immune and metabolic derangement). Usually, it is
difficult to achieve complete improvement of underlying
conditions because the majority of patients reach the
hospital when mucormycosis is fully advanced. There is
no evidence that combination therapy with amphoteri-
cin B+ posaconazole is advantageous. However, the use
of an echinocandin + liposomal amphotericin B formu-
lation is a better option as indicated by both animal and
human data.31–35
Conflict of interest
All authors declare no conflicts of interest.
References
1 Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and en-
tomophthoramycosis (zygomycosis) and nomenclature of the disease:
molecular mycologic perspectives. Clin Infect Dis 2012; 54(Suppl. 1):
S8–15.
2 Chayakulkeeree M, Ghannoum MA, Perfect JR. Zygomycosis: the re-
emerging fungal infection. Eur J Microbiol Infect Dis 2006; 25: 215–
29.
3 Ibrahim AS, Kontoyiannis DP. Update on mucormycosis pathogene-
sis. Curr Opin Infect Dis 2013; 26: 508–15.
4 Chakrabarti A, Das A, Mandal J et al. The rising trend of invasive
zygomycosis in patient with uncontrolled diabetes mellitus. Med
Mycol 2006; 44: 335–42.
5 Bonifaz A, Macias B, Paredes-Farrera F, Arias P, Ponce RM, Araiza
J. Palatal zygomycosis: experience of 21 cases. Oral Dis 2008; 14:
569–74.
6 Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoy-
iannis DP. Epidemiology and clinical manifestations of mucormyco-
sis. Clin Infect Dis 2012; 54(Suppl. 1): S23–34.
7

Alvarez E, Sutton DA, Cano J et al. Spectrum of zygomycete species
identified in clinically significant specimens in the United States. J
Clin Microbiol 2009; 47: 1650–6.
8 Kontoyiannis DP, Lewis RE. Invasive zygomycosis: update on patho-
genesis, clinical manifestations, and management. Infect Dis Clin
North Am 2006; 20: 581–607.
9 Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and out-
come of zygomycosis: a review of 929 reported cases. Clin Infect Dis
2005; 41: 634–53.
10 Prasad PA, Vaughan AM, Zaoutis TE. Trends in zygomycosis in chil-
dren. Mycoses 2012; 55: 352–6.
11 Hern
andez-Maga~ na R, G
omez-Barreto D, Salgado MA, Bonifaz A, de
la Torre AS. Mucormicosis rinoorbitaria nosocomial causada por Rhi-
zopus oryzae en lactante desnutrido. Bol Med Hosp Infant Mex 2001;
58: 35–47.
12 Roilides E, Zaoutis TE, Walsh TJ. Invasive zygomycosis in neonates
and children. Clin Microbiol Infect 2009; 15(Suppl. 5): 50–54.
13 Dehority W, Willert J, Pong A. Zygomycetes infections in pediatric
hematology oncology patients: a case series and review of the litera-
ture. J Pediatr Hematol Oncol 2009; 31: 911–9.
14 Nirmala SV, Lalitha V, Sivakumar N, Kumar KK, Srikanth M. Muco-
rmycosis associated with juvenile diabetes. J Indian Soc Pedod Prev
Dent 2011; 29(Suppl. 2): S87–91.
15 D€abritz J, Attarbaschi A, Tintelnot K et al. Mucormycosis in paediat-
ric patients: demographics, risk factors and outcome of 12 contempo-
rary cases. Mycoses 2011; 54: 785–8.
16 Phulpin-Weibel A, Rivier A, Leblanc T, Bertrand Y, Chastagner P.
Focus on invasive mucormycosis in paediatric haematology oncology
patients: a series of 11 cases. Mycoses 2013; 56: 236–40.
83
A. Bonifaz et al.
17 Popa G, Blag C, Sasca F. Rhinocerebral mucormycosis in a child with
acute lymphoblastic leukemia: a case report. J Pediatr Hematol Oncol
2008; 30: 163–5.
18 Song KR, Wong MS, Yeung C. Primary cutaneous zygomycosis in an
immunodeficient infant: a case report and review of the literature.
Ann Plast Surg 2008; 60: 433–6.
19 Bitar D, Che D.
Epid
emiologie des mucormycoses en France m
etropol-
itaine, 1997–2010. Med Sci (Paris) 2013; 29: 7–12.
20 Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of
mucormycosis. Clin Infect Dis 2012; 54(Suppl. 1): S16–22.
21 Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes
mellitus: a review of pathogenesis. Indian J Endocrinol Metab 2012;
16(Suppl. 1): S27–36.
22 Moye J, Rosenbloom AL, Silverstein J. Clinical predictors of muco-
rmycosis in children with type 1 diabetes mellitus. J Pediatr Endocri-
nol Metab 2002; 15: 1001–4.
23 G
omez-D
ıaz RA, P
erez-P
erez G, Hern
andez-Cuesta IT et al.
Incidence of type 1 diabetes in Mexico: data from an institutional
register 2000-2010. Diabetes Care 2012; 35: e77. doi: 10.2337/
dc12-0844.
24 Tarkan O, Karag€ un B, Ozdemir S et al. Endonasal treatment of acute
invasive fungal rhinosinusitis in immunocompromised pediatric
hematology-oncology patients. Int J Pediatr Otorhinolaryngol 2012;
76: 1458–64.
25 Skiada A, Petrikkos G. Cutaneous mucormicosis. Skinmed 2013; 11:
155–9.
26 Bonifaz A, V
azquez-Gonz
alez D, Tirado-S

anchez A, Ponce Olivera R.
Cutaneous zygomycosis. Clin Dermatol 2012; 30: 413–9.
84
27 Velepic M, Manestar D, Ahel VV, Linsak Z, Malvi
c G. Mucormycosis
of the nasal ala in a leukemic (M7 AML) child. Is surgery of the
nasal defect indicated? Coll Antropol 2012; 36: 535–7.
28 Bonifaz A, Barr
on T, Collazo-Jaloma J. Zigomicosis (mucormicosis)
cut
anea en paciente con leucemia. Actas Dermosifiliogr 2002; 93:
514–7.
29 Gonz
alez-Abad MJ, Alonso Sanz M. Zygomycosis in children: dissemi-
nated infection caused by Cunninghamella bertholletiae. Arch Bronco-
neumol 2013; 49: 35.
30 Maron GM, Hayden RT, Rodriguez A et al. Voriconazole prophylaxis
in children with cancer: changing outcomes and epidemiology of
fungal infections. Pediatr Infect Dis J 2013; 32: e451–5.
31 Almannai M, Imran H, Estrada B, Siddiqui AH. Successful treatment
of rhino-orbital mucormycosis with posaconazole and hyperbaric
oxygen therapy. Pediatr Hematol Oncol 2013; 30: 184–6.
32 Egelund EF, Egelund TA, Ng JS, Wassil SK, Peloquin CA. Posaconazole
pharmacokinetics in a 2-year-old boy with rhino-cerebral-orbital zygo-
mycosis. Pharmacotherapy 2013; 33: e1–8. doi:10.1002/phar.1172.
33 Ibrahim AS, Gebremariam T, Fu Y, Edwards JE Jr, Spellberg B. Com-
bination echinocandin-polyene treatment of murine mucormycosis.
Antimicrob Agents Chemother 2008; 52: 1556–8.
34 Ibrahim AS, Gebremariam T, Luo G et al. Combination therapy of
murine mucormycosis or aspergillosis with iron chelation, polyenes,
and echinocandins. Antimicrob Agents Chemother 2011; 55: 1768–
70.
35 Reed C, Bryant R, Ibrahim AS et al. Combination polyene-caspofun-
gin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis
2008; 2008: 364–71.
© 2014 Blackwell Verlag GmbH
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