634 • CID 2005:41 (1 September) • Roden et al.
M A J O R A R T I C L E
Epidemiology and Outcome of Zygomycosis:
A Review of 929 Reported Cases
Maureen M. Roden,1Theoklis E. Zaoutis,2,3,4Wendy L. Buchanan,1Tena A. Knudsen,1Tatyana A. Sarkisova,1
Robert L. Schaufele,1Michael Sein,1Tin Sein,1Christine C. Chiou,6Jaclyn H. Chu,2Dimitrios P. Kontoyiannis,5
and Thomas J. Walsh1
1Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland;
of Philadelphia, and
of Medicine, Philadelphia, Pennsylvania;
2Division of Infectious Diseases, The Children’s Hospital
4Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School
5M. D. Anderson Cancer Center, University of Texas, Houston; and
3Department of Pediatrics and
6National Yang Ming University,
hensive literature review that describes the epidemiology and outcome of this disease.
We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929
eligible cases. We included in the database only those cases for which the underlying condition, the pattern of
infection, the surgical and antifungal treatments, and survival were described.
The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were
36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and
66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and
cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of
patients with disseminated disease died, 85% with gastrointestinalinfectiondied,and76%withpulmonaryinfection
died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority
of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently
in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hema-
togenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by
deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324
of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone,
and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection
due to Cunninghamella species and disseminated disease were independently associated with increased rates of
death (odds ratios, 2.78 and 11.2, respectively).
Outcome from zygomycosis varies as a function of the underlying condition, site of infection,
and use of antifungal therapy.
Zygomycosis is an increasingly emerging life-threatening infection. There is no single compre-
Zygomycosis has emerged as an increasingly important
pathogen during the past decade [1–5]. This increase
has been particularly evident in hematopoieticstemcell
transplant recipients and patients with hematological
malignancies [6–12]. Unlike other filamentous fungi
that are largely opportunistic in patients with cancer,
transplant recipients, and patients with inherited im-
munodeficiencies, zygomycosis also can be a frequently
Received 27 January 2005; accepted 18 April 2005; electronically published 29
Reprints or correspondence: Dr. Thomas J. Walsh, Pediatric Oncology Branch,
National Cancer Institute, CRC, 1W, 1-5740, 10 Center Dr., Bethesda, MD 20892
Clinical Infectious Diseases 2005;41:634–53
? 2005 by the Infectious Diseases Society of America. All rights reserved.
lethal infection in hosts with greater immunocompe-
tency, such as those with diabetes mellitus [13–23],
drug users (IDUs) [33–39], and those with no apparent
immune impairment [40–46].
To date, there has been no definitive, comprehensive
review of the literature on zygomycosis to guide our
understanding of the epidemiology and outcome of
zygomycosis in the general population. We therefore
reviewed the English-language literature for all cases of
zygomycosis, from the original case report in 1885 to
the present. In this review, we sought to understand
the distribution of infection within the general popu-
lation and to ascertain whether the patternsofinfection
are associated with specific host factors and outcomes.
Epidemiology of Zygomycosis • CID 2005:41 (1 September) • 635
zygomycosis, 504 of whom died.
Demographic and clinical characteristics of 929 patients with
Characteristic All patients
No underlying condition at time of in-
fection, cause of infection
Underlying condition at time of infection
Solid organ transplantation
Injection drug use
Bone marrow transplantation
Low birth weight infant
Diarrhea and malnutrition
Systemic lupus erythematosus
aData are no. of patients with the characteristic who died/total no. with the charac-
bIncludes hepatic disease, hematologic disorders,metabolicacidosis,tuberculosis,and
Data are proportion (%) of patients, unless otherwise specified.
We initiated our search by reviewing all references from the
chapters of major books written on the subject of zygomycosis.
We then carefully scrutinized the references for single case re-
ports or case series. We then expanded this initial review by a
MEDLINE search using the following key words: zygomycosis,
mucormycosis, phycomycosis, Rhizopus, Mucor, Rhizomucor,
Cunninghamella, Absidia, Apophysomyces, Syncephalastrum,
idiobolus. After this initial series of reports was reviewed, the
individual references listed in each publication were again re-
viewed for ascertainment of additional case reports.
Criteria for inclusion of zygomycosis case reports
Only those case reports that included data on the following 6
variables were included in our review.
to be confirmed either histologically or by culture.Information
about whether the infection was documented premortem or
postmortem also was required.
Anatomical location of infection.
primary site of infection at the time of diagnosis and whether
the infection remained localized or disseminated was required.
Disseminated infection was defined as infection at ?2 non-
contiguous sites. Patients with disseminated infection at the
time of diagnosis for which the primary site of infection was
impossible to identify were classified as having generalized dis-
seminated infection. Patients with cutaneous infection were
subcategorized into 3 groups. Patients in whom the infection
was confined to the cutaneous or subcutaneous tissue were
defined as having localized disease. Patients with invasion into
muscle, tendon, or bone were classified as having deep exten-
sion of infection. Patients with cutaneous disease involving
Documentation of the
636 • CID 2005:41 (1 September) • Roden et al.
Incidences of zygomycosis over 6 decades (1940–1999), by host population
another noncontiguous site were defined as having dissemi-
nated infection. Patients with pulmonary infection were sub-
categorized in a similar manner, as follows: those with disease
confined to the lungs were classified as having localized infec-
tion; those with disease that extended to the chest wall, pul-
monary artery, aorta, or heart were defined as having deep
extension of infection; and those with demonstrated involve-
ment of a noncontiguous site were defined as having dissem-
We were especially careful to subcategorize patients with si-
nus involvement, because we found “rhinocerebral” to be an
overused term for this infection. Consequently, we distin-
guished patients withtruecerebralinvolvementfromthosewith
localized sinus disease. We also separately categorized patients
on the basis of sino-orbital involvement and sinopulmonary
disease. Patients with disease confined to the paranasal sinuses
were defined as having sinusitis; those with disease in the par-
anasal sinuses and infiltrating the orbit were defined as having
sino-orbital infection; those with disease in the paranasal si-
nuses and the brain were categorized as having rhinocerebral
infection, with cerebral involvement defined as tissue invasion
demonstrated histologically or by culture during life or at au-
topsy, radiological evidence of disease by either CT or MRI, or
severe neurological impairment; and those with disease in the
paranasal sinuses and lungs were defined as having sinopul-
Documentation of the primary un-
derlying condition or of immunosuppression was required for
each reported case, unless the patient was described as having
no underlying condition.
the presence or absence of both surgery and antifungal therapy
Documentation of antifungal therapy.
with a documented absence or specific presence of antifungal
therapy were included in the review. When not specified, we
estimated the approximate duration of amphotericin B therapy
for adult patients by dividing the total dose by 70 kg and
assuming a dosage of 1 mg/kg per day.
Mortality was assessed as all-cause mortality
during the course of zygomycosis.
Only those cases that specified
Only those patients
Filemaker Pro software, version 5.5 (Filemaker), was used to
develop a database of categorical and continuous variables.The
categorical variables included sex, underlying diagnosis, dia-
betes (type and presence of ketoacidosis), neutropenic status,
infecting organism, diagnostic method used for recovery of
infecting organism, premortem or postmortem diagnosis, in-
fection site (focal or disseminated disease), surgery, hyperbaric
oxygen therapy, immunomodulation, and outcome. The con-
tinuous variables included year of diagnosis, year of case pub-
lication, age of patient, and dose and/or duration of antifungal
Patterns of zygomycosis, by host population
638 • CID 2005:41 (1 September) • Roden et al.
cosis, 504 of whom died.
Infection patterns among 929 patients with zygomy-
Type of infection, by site
of all patients
No. of patients
with the infection
who died/total no.
with the infection (%)
Other solid organ
because patients with infection at 11 site are counted more than once. Thus,
988 sites are reported for all patients, and 561 sites are reported for patients
aPatients with rhinocerebral infection and those with localized cerebral in-
fection together constituted 283 patients (30%).
bIncludes peritoneum, mastoid, oral mucosa, bone, and bladder.
Patient counts in each column total to more than the n values
therapy. When available, additional information regarding se-
rum ferritin, transferrin, and transferrin saturation levels, as
well as glucose and bicarbonate levels, were recorded.
Univariate analyses were conducted to determine the associa-
tion between potential risk factors and death. Categorical var-
iables were compared by x2analysis or Fisher’s exact test,
whereas continuous variables were compared by the Wilcoxon
rank-sum test. All variables with a P value of !.20 on univariate
analysis were considered for inclusion in a multivariate model,
as were those variables noted to be confounders on stratified
analysis. Multivariate analysis was performed using logistic re-
gression methods. Survey estimation was applied to the logistic
regression models, to adjust for the modest degree of case clus-
tering among the reporting sites. Clustering was evident from
estimates of statistically significant but modest interclass cor-
relation (by site). The analyses used standard algorithms as
described by Korn and Graubard  to determine variance
estimates for this correlation. Construction of the multivariate
model began with inclusion of certain variables (i.e., dissemi-
nated disease and therapy) considered to be important on the
basis of a priori hypotheses. Reported CIs are therefore some-
what more conservative (wider) and P values are somewhat
larger than would be estimated by conventional logistic re-
gression methods. A 2-tailed P value of !.05 was considered
to be statistically significant. All statistical calculations were
performed using standard programs in Stata, version 7.0
The first case of zygomycosis reported in the literature was by
Paultauf in 1885 . This case, however, did not meet the
predefined eligibility criteria and, consequently, was not in-
cluded in our database. The first case to be included was re-
ported in 1940. A total of 1049 individual cases of zygomycosis
from 1940 through 2003 were identified. Of these, 120 cases
were excluded from the database because they did not meet
the stringent predefined inclusion criteria. The total database
thus consisted of 929 cases (in 1 patient each) reported in 459
published reports [14–476].
and their associated all cause mortality are summarized intable
1. The mean age was 38.8 years, and the median age was 40.0
years (range, 0.005–80 years). A total of 65% of allZygomycetes
infections occurred in males. The overall mortality in the total
population was 54% (504 of 929 patients).
Diabetes was the most common underlying condition. Only
68 patients (20%) with diabetes had type I diabetes, and of
these, 33 (48%) had documented ketoacidosis. Conversely,
most patients with diabetes in this review had type II diabetes
(), with 64 (34%) having documented ketoacidosis. In
n p 187
54 (16%) of 337 patients with diabetes, zygomycosis presented
as the diabetes-defining illness. The second largest patientpop-
ulation consisted of persons who had no primary underlying
disease at the time of infection. Among 154 patients with ma-
lignancy, 147 (95%) had a hematological malignancy. There
were only 7 cases of zygomycosis reported in patients with a
Secular trends in reported hosts.
the reporting of zygomycosis in all underlying host populations
during the study period (figure 1). Diabetes was the most com-
monly reported underlying condition in each decade.However,
an increasing proportion of other host populations, including
those with malignancy, recipients of bone marrow transplants,
The underlying conditions
There was an increase in
Epidemiology of Zygomycosis • CID 2005:41 (1 September) • 639
Percentages of zygomycosis cases documented by culture since the 1940s, by decade
recipients of deferoxamine, IDUs, and patients with no un-
derlying condition becomes apparent in the 1980s and 1990s.
Sites and patterns of infection.
tion at the time of initial diagnosis varied as a function of the
host population (figure 2). Sinus involvement consisting of
rhinocerebral, sinus, and sino-orbital infections constitutedthe
majority of infections (222 [66%] of 337) in patients with
diabetes. This differs from the pattern of infection in persons
with no underlying condition, in which cutaneouszygomycosis
constituted one-half of all cases. By further comparison, pul-
monary zygomycosis constituted more than one-half of all sites
of infection in patients with malignancy and recipients of bone
marrow transplants. Sinus involvement was the second most
common pattern of infection in this patient population. Pa-
tients undergoing solid organ transplantation had another dis-
tinctive pattern, with relatively similar frequencies of pulmo-
nary and sinus infections. On the other hand, patientsreceiving
deferoxamine therapy presented more frequently with gener-
alized disseminated zygomycosis, compared with other host
categories. Finally, cerebral zygomycosis was the most common
presenting pattern of infection in IDUs. The pattern of cerebral
zygomycosis in IDUs was hematogenous and was seldom as-
sociated with rhinocerebral infection.
The patterns of infection and their associated all-cause mor-
tality are detailed in table 2. The paranasal sinuses were the
most common site of infection, presenting in 39% of cases.
Rhinocerebral infection was the most commonly reported pat-
tern of sinus zygomycosis. Independent predictors for sinus
zygomycosis were diabetes type 1 (OR, 4.04; 95% CI, 2.36–
6.90), diabetes type 2 (OR, 6.35; 95% CI, 3.89–10.36), and
injection drug use (OR, 0.15; 95% CI, 0.04–0.51). Pulmonary
The primary site of infec-
disease was the second most common presenting pattern. Ap-
proximately one-half of all cases were restricted to the lung,
whereas the remaining cases were either disseminated or com-
plicated by deep extension into the chest wall, pulmonary ar-
tery, or heart. Independent risk factors for pulmonary zygo-
mycosis were infection with Cunninghamellaspecies(compared
with infection with Rhizopus species) (OR, 7.75; 95% CI, 2.44–
24.58), neutropenia (OR, 2.28; 95% CI, 1.26–4.11), and receipt
of a solid organ transplant (OR, 3.41; 95% CI, 1.41–8.20).
Cutaneous involvement was the presenting pattern in 176
(19%) of 929 patients. Penetrating trauma was reported for 60
(34%) of these patients, dressings were reported for 26 (15%),
surgery was reported for 26 (15%), burns were reported for
11 (6%), motor vehicle accident was reported for 5 (3%), and
falls were reported for 5 (3%). The histories for the remaining
42 patients (24%) were not well described. Most cases were
localized to the integument. However, deep extension to bone,
tendon, or muscle occurred in 42 (24%) of 176 cases, and
organs occurred in 35 (20%). Hematogenous dissemination
from other organs to skin occurred rarely, in only 6 cases (3%).
The majority of patients with cutaneous infection were either
nonneutropenic or had no underlying condition. Independent
risk factors for localized cutaneous infection were female sex
(OR, 2.27; 95% CI, 1.46–3.55), no underlying condition (OR,
2.60; 95% CI, 1.32–5.14), prior surgery (OR, 5.40; 95% CI,
1.84–15.86), and HIV infection (OR, 2.62; 95% CI, 1.01–6.79).
There were 283 patients with CNS infection, of which 69%
had rhinocerebral infection, 16% had localized cerebral infec-
tion, and 15% had hematogenous dissemination of infection
from other organs to the brain. Both rhinocerebral infection
640 • CID 2005:41 (1 September) • Roden et al.
mycosis, 219 of whom died.
Microbiological findings for 465 patients with zygo-
of all patients
No. of patients
who died/total no.
with the organism (%)
pendent variables, including species-related host factors and patterns of
Interspecies differences in mortality may be due to other code-
sex in 465 cases of culture-confirmed zygomycosis.
Relationship between microbiologic findings and male
No. of cases
of cases (%)
and localized cerebral infection were associated withamortality
of 62%. Of patients with localized cerebral infection, mostwere
IDUs who were independently associated withthedevelopment
of primary CNS disease (OR, 80.25; 95% CI, 26.69–241.28).
There were no patients with diabetes who had hematogenous
dissemination to the brain. Instead, all CNS infections in pa-
tients with diabetes occurred in those with rhinocerebral
Gastrointestinal infection occurred in 65 patients (7%). The
rate of dissemination to other noncontiguous organs was 38%
(25 of 65 patients). Mortality was high, primarily because of
bowel perforation. The infection occurred predominantly in
low birth weight infants, patients with diarrhea and malnutri-
tion, and patients receiving peritoneal dialysis.
The risk for development of disseminated zygomycosis from
any site varied as a function of host characteristics.Independent
risk predictors were burns (OR, 6.26; 95% CI, 1.16–33.81),
prematurity (OR, 2.85; 95% CI, 1.26–6.43), deferoxamine use
(OR, 2.76; 95% CI, 1.66–4.59), diabetes (OR, 0.29; 95% CI,
0.17–0.50), no underlying condition (OR, 0.47; 95% CI, 0.25–
0.91), and HIV infection (OR, 0.15; 95% CI, 0.03–0.63).
Microbiologic and histopathologic findings.
had infection documented either histologically or by culture.
A positive culture result was obtained in 50% of cases (table
3). There was a clear increase in culture positivity over time,
with 71% of all cases since 2000 diagnosed on the basis of
culture results (figure 3). Among the 465 cases with a culture
positive for a Zygomycetes organism, Rhizopus species were the
most commonly recovered organisms, with Rhizopus oryzaethe
most frequently recovered species.
Sex and zygomycosis.
Zygomycosis occurred primarily in
males (605 [65%] of 929 cases). The following genera were
clearly associated with infection in males, constituting 178%
of infections in this group: Basidiobolus, Cunninghamella, Ab-
sidia, and Apophysomyces (table 4).
Entomophthorales organisms caused 7.2% of all zygomy-
coses in this review. The order Entomophthorales differedfrom
the order Mucorales in overall survival (69% vs. 52%) and in
the frequency of persons with no underlying condition (69%
vs. 50%). Of infections due to Conidiobolus species, 5 (50%)
of 10 were cutaneous. Of infections due to Basidiobolusspecies,
7 (78%) of 9 were gastrointestinal.
Of the 929 cases reviewed, 596 (64%) were
treated with some form of antifungal chemotherapy (table 5).
Survival in this group was 62% (369 of 596 patients). Of these
596 patients, 532 (89%) received amphotericin B deoxycholate,
with an overall survival of 61%. Survival was 57% (51 of 90
patients) for those treated with surgeryalone;survivalincreased
to 70% (328 of 470 patients) for those treated with a combi-
nation of surgery and antifungal chemotherapy. A total of 241
patients (26%) received no treatmentfortheirinfection.Within
this subgroup, the survival rate was 3% (8 of 241 patients).
Analysis of survival by decaderevealedthatover-
all mortality improved from 84% in the 1950s to 47% in the
1990s (figure 4). However, mortality due to zygomycosis has
remained essentially unchanged since the 1960s, when ampho-
tericin B deoxycholate was widely introduced (figure 5).
Table 6 summarizes results of the multivariate regression
analysis of risk factors for mortality among all patients. Sig-
nificant risk factors for mortalityincludeddisseminateddisease,
Epidemiology of Zygomycosis • CID 2005:41 (1 September) • 641
Treatment administered to 929 patients with zygomycosis, 425 of whom
of all patients
No. of patients
who survived/total no.
the treatment (%)
Amphotericin B formulation
Itraconazole, ketoconazole, or posaconazole
No antifungal therapy
Surgery and antifungal chemotherapy
Granulocyte colony-stimulating factor
Mortality due to zygomycosis since the 1940s, by decade
renal failure, and infection with Cunninghamella species. Con-
versely, type I diabetes and no underlying condition were in-
dependently associated with a reduced risk of death. Compared
with no receipt of antifungal therapy, all forms of antifungal
therapy were also significantly associated with a reduced risk
of mortality. Patients who underwent surgery as primary ther-
apy were also significantly more likely to survive. Pulmonary,
rhinocerebral, kidney, and gastrointestinal infection were as-
sociated with the highest risks of mortality.
Zygomycosis was first reported as a cause of human disease in
1885 . Unlike other filamentous fungal pathogens that tar-
get immunocompromised hosts, Zygomycetes organismsinfect
a broader and more heterogeneous population. In this review,
persons with no underlying condition and patients with dia-
betes represented 150% of all infected patients. In the past 20
years, there also has been an emergence of this infection in the
more classically defined immunocompromised risk groups,
such as patients with hematological malignancy, recipients of
a bone marrow transplant, and recipients of a solidorgantrans-
Zygomycetes organisms are unique among filamentous fun-
gi because of their disproportionately high capacity to cause
devastating disease in persons with no underlying condition.
Among persons with no underlying condition who had a his-
642 • CID 2005:41 (1 September) • Roden et al.
Median duration of polyene therapy for patients with zygomycosis who survived or who died, by host population
patients with zygomycosis.
Multivariate model of risk factors for mortality among
VariableOR (95% CI)P
Extent of infection
No underlying condition
Amphotericin B deoxycholate only
Lipid amphotericin only
Amphotericin formulation and azole
Surgery as primary therapy
of site-specific infections are (with cutaneous infections as the reference):
pulmonary infection (OR, 7.50; 95% CI, 2.84–19.80;
infection (OR, 6.39; 95% CI, 2.64–15.48;
8.30; 95% CI, 2.54–27.16; ), and gastrointestinal infection (OR,22.51;Pp .001
95% CI, 5.50–92.14; ).Pp!.001
Additional risk factors included within a similar model for analysis
), kidney infection (OR,Pp!.001
tory of burns, surgery, or trauma, the majority (63 [73%] of
87) presented with cutaneous disease. In the subgroup of per-
sons with no underlying condition, only 25 (28%) of 89 pre-
presented with deeply invasive infection.
Cutaneous inoculation from a Zygomycetes organism may
have underestimated consequences. Of all cutaneous infections
in this review, 43 (24%) of 176 deeply extended to tendon,
muscle, or bone. Moreover, an additional 35 (20%) of 176
patients with cutaneous disease developed hematogenous dis-
semination from the original cutaneous site to another organ,
resulting in an overall mortality of 94% (33 of 35 patients) in
this subgroup. Unlike other filamentous fungi that will he-
matogenously disseminate from another organ to skin, we
found converse behavior in this review. There were 220 cases
of hematogenously disseminated infection, yet only 6 had doc-
umented cutaneous involvement. Of the 4 cases in which cul-
ture was performed, 3 were due to Rhizomucor pusillus, which,
overall, is a relatively uncommon pathogen [49–51].
Cerebral infection was the most common presentation of
zygomycosis in IDUs. This pattern occurred in the absence of
sinusitis or rhinocerebral disease and appears tohavedeveloped
hematogenously. Because Zygomycetes organisms are ubiqui-
tous, contamination of injected illicit drugs seems to be likely.
If some of the injected sporangiospores are not adequately fil-
tered by the pulmonary capillary bed, they will enter the sys-
temic arterial circulation, where ∼25% of the cardiac output is
distributed to the brain. Particulate material the size of spor-
angiospores tend to distribute either to the gray-white junction
of the brain or to the basal ganglia via the striatal arteries. The
vast majority of the infections we reviewed presented in the
We found that patterns of infection differ as a function of
host characteristics. The relationships between persons with no
underlying condition and cutaneous involvement and between
IDUs and cerebral involvement seems to be logical. However,
the strong association between both malignancy and bonemar-
Epidemiology of Zygomycosis • CID 2005:41 (1 September) • 643
between diabetes and sinus involvement is more complicated.
Perhaps one sees a preponderance of pulmonary disease in the
population with malignancies as the result of chemotherapy-
related defects in innate pulmonary host defenses that are as-
sociated with neutropenia and with chemotherapy-induced
mucociliary dysfunction. The factors contributing to sinus in-
volvement in patients with diabetes maybemoremultifactorial.
Patients with diabetes have more microvascular disease, and
perhaps this, in concert with the delicate architecture of the
sinuses, may result in more tissue destruction and local
The patterns of infection due to deferoxamine demonstrated
the highest level of generalized disseminated infection (23%),
compared with any other pattern. This finding underscores the
importance of iron in the virulence of Zygomycetes organisms.
When circulating deferoxamine molecules bind to host iron,
the deferoxamine serves as a sideophore to the Zygomycetes
organism. This iron-enriched systemic milieu tips the host-
parasite balance in favor of the pathogen.
This study documents that the capacity to recover these or-
ganisms by culture has significantly improved over time. This
improvement may be due to better training among mycology
technologists, a greater understanding of specimen processing
in the laboratory, improved culture techniques, and increased
access to sophisticated reference laboratories.
The reason for a higher prevalence of Zygomycetesinfections
among males is unclear. There is mycologic precedent for this
predisposition, as observed in the protective role of estrogen
in paracoccidioidomycosis . The potential role of estrogen
in Zygomycetes infection has not yet been explored.
There were 157 pediatric cases in this review. Underlying
host factors differed between adults and children: 17% of pe-
diatric infections occurred in low birth weight infants,and26%
were associated with diarrhea and malnutrition.
Most patients in this review who were treated withantifungal
chemotherapy received amphotericin B or one of its lipid for-
mulations. This is not surprising, because amphotericin B has
been essentially the only agent active against most Zygomycetes
species. There did appear to be some added benefit to receiving
surgery for the management of these infections. However, one
must exercise caution in extrapolating treatment choices on the
basis of these data, because all of the data are retrospective and
may be subject to a period effect (i.e., a change in the rate of
a condition irrespective of age and birth date) and publication
bias. Nevertheless, multivariate analysis clearly demonstrates
that antifungal therapy and surgery are independently associ-
ated with a decreased risk of mortality, with ORs of 0.9–0.24.
There has been little change in the overall mortality during the
past 40 years, since the introduction of amphotericin B. As
recognition of host groups and their risk factors for zygomy-
cosis increases, earlier intervention with antifungaltherapymay
improve the outcome of this devastating infection.
and Enzon Pharmaceuticals (to M.M.R.).
Potential conflicts of interest.
Schering Plough Research Institute (to M.M.R.)
All authors: no conflicts.
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