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Journal of Clinical Microbiology, December 2000, p. 4569-4576, Vol. 38, No. 12
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Acrophialophora fusispora Brain Abscess
in a Child with Acute Lymphoblastic Leukemia: Review of Cases and
Taxonomy
I. Z.
Al-Mohsen,1,*
D. A.
Sutton,2
L.
Sigler,3
E.
Almodovar,1
N.
Mahgoub,1
H.
Frayha,1
S.
Al-Hajjar,1
M. G.
Rinaldi,2 and
T.
J.
Walsh4
King Faisal Specialist Hospital & Research
Center, Riyadh, Saudi Arabia1; Fungus
Testing Laboratory, University of Texas Health Science Center, San
Antonio, Texas2; University of Alberta
Microfungus Collection, Edmonton, Alberta,
Canada3; and Pediatric Branch, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland4
Received 6 June 2000/Returned for modification 10 July
2000/Accepted 21 September 2000
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ABSTRACT |
A 12-year-old girl with acute lymphoblastic leukemia was referred
to King Faisal Specialist Hospital and Research Center. The diagnosis
without central nervous system (CNS) involvement was confirmed on
admission, and chemotherapy was initiated according to the Children
Cancer Group (CCG) 1882 protocol for high-risk-group leukemia. During
neutropenia amphotericin B (AMB) (1 mg/kg of body weight/day) was
initiated for presumed fungal infection when a computed tomography (CT)
scan of the chest revealed multiple nodular densities. After 3 weeks of
AMB therapy, a follow-up chest CT revealed progression of the pulmonary
nodules. The patient subsequently suffered a seizure, and a CT scan of
the brain was consistent with infarction or hemorrhage. Because of
progression of pulmonary lesions while receiving AMB, antifungal
therapy was changed to liposomal AMB (LAMB) (6 mg/kg/day). Despite 26 days of LAMB, the patient continued to have intermittent fever, and CT
and magnetic resonance imaging of the brain demonstrated findings consistent with a brain abscess. Aspiration of brain abscess was performed and the Gomori methenamine silver stain was positive for
hyphal elements. Culture of this material grew Acrophialophora fusispora. Lung biopsy showed necrotizing fungal pneumonia with negative culture. The dosage of LAMB was increased, and itraconazole (ITRA) was added; subsequently LAMB was discontinued and therapy was
continued with ITRA alone. The patient demonstrated clinical and
radiological improvement. In vitro, the isolate was susceptible to low
concentrations of AMB and ITRA. A. fusispora is a
thermotolerant, fast-growing fungus with neurotropic potential. We
report the first case of human infection involving the CNS.
Acrophialophora resembles Paecilomyces but
differs in having colonies that become dark and in the development of
phialides along the sides or at the tips of echinulate brown
conidiophores. Conidia are borne in long chains and are smooth or
ornamented with fine-to-coarse echinulations, sometimes in spiral
bands. The taxonomy of the genus Acrophialophora is
reviewed, and Acrophialophora nainiana and
Acrophialophora levis are considered as synonyms of
A. fusispora.
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INTRODUCTION |
During the past 2 decades invasive
fungal infections have emerged as a major cause of morbidity and
mortality in an expanding spectrum of high-risk immunocompromised
patients (27). The numbers and types of saprobic and
opportunistic filamentous fungi that have been documented as etiologic
agents of invasive diseases continue to escalate (15, 18,
26). Candida, Aspergillus, Trichosporon, and
Fusarium species are the leading fungal pathogens in
patients with hematologic malignancies (1), but less common molds are increasingly being documented as occasional pathogens (2, 12). Acrophialophora fusispora is a
thermotolerant soil fungus that grows well at 45°C or higher
temperatures. It has been reported once from a human corneal infection
(22) and implicated in disseminated infection involving the
brain in two dogs. In one of the latter cases, the etiologic agent was
originally identified as Scopulariopsis chartarum
(29), suggesting that A. fusispora may go
unrecognized by diagnostic laboratories. We describe the first case of
human cerebral brain abscess due to A. fusispora and use
this case to compare microbiologic features and antifungal susceptibilities of pathogenic and nonpathogenic isolates and to review
the taxonomy of the genus Acrophialophora.
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CASE REPORT |
Clinical course.
The patient was a 12-year-old Sudanese girl
diagnosed with acute lymphoblastic leukemia on 12 July 1998. She
received four courses of induction chemotherapy with vincristine and
prednisone for 4 weeks in Sudan prior to admission to the King Faisal
Specialist Hospital and Research Center (KFSH&RC) on 14 August 1998. The diagnosis of acute lymphoblastic leukemia without central nervous system (CNS) involvement was confirmed, and chemotherapy was
initiated according to the CCG 1882 protocol for high-risk
leukemia. This protocol included weekly vincristine and
daunomycin and daily dexamethazone. After 2 weeks of chemotherapy,
hyperglycemia and hypertension developed, following which dexamethasone
was changed to prednisone to complete the 4 weeks of induction therapy.
The patient received nine doses of asparaginase over 4 weeks. A bone marrow aspirate at 28 days postinduction showed remission of leukemia. The consolidation phase of chemotherapy consisted of cytosine arabinoside, 6-mercaptopurine, and cyclophosphamide, as well as intrathecal methotrexate. Subsequently the patient continued on maintenance chemotherapy.
At her initial presentation to the KFSH&RC, the patient was febrile
with no focus of infection. Empirical broad-spectrum antibiotics (ceftazidime and gentamicin) were initiated. Subsequently vancomycin was added. As her fever persisted during neutropenia, while she was on
broad-spectrum antibiotics, amphotericin B (AMB), 1 mg/kg of body
weight/day, was initiated on the 5th day for presumed fungal infection
when the chest computed tomography (CT) scan revealed multiple nodular
densities. A lung biopsy was deferred because of coagulopathy. After 3 weeks of AMB therapy, a follow-up chest CT scan revealed an increase in
size and numbers of pulmonary nodules (Fig.
1). The patient subsequently suffered a
seizure, and a CT scan of the brain was consistent with infarction or
hemorrhage. Antifungal therapy was changed to liposomal AMB (LAMB)
(AmBisome), 6 mg/kg/day, due to the progression of pulmonary lesions
while receiving AMB. Despite 26 days of LAMB, the patient continued to
have intermittent fever, and a follow-up CT and magnetic resonance imaging of the brain demonstrated a ring-enhancing lesion at the site
of previously reported infarct. These findings were consistent with a
brain abscess in the parieto-occipital area (Fig.
2). Aspiration of the brain abscess was
performed. Thick yellowish pus was drained from the abscess, and the
Gomori methenamine silver (GMS) stain was positive for a large number
of septate hyphae (Fig. 3). Culture of
the brain abscess aspirate grew a fungus closely resembling a
Paecilomyces species.
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FIG. 2.
(A) CT of the brain with contrast demonstrating the
brain lesion in the left parieto-occipital region. (B) Brain magnetic
resonance imaging with contrast showing the ring-enhancing lesion in
the left parieto-occipital region with minimal surrounding edema.
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The patient also underwent right thoracotomy, and there was a
cavitating fungal lesion in the lower lobe penetrating through
the
diaphragm. Histopathology of this lesion was consistent with
necrotizing fungal pneumonia with septate hyphae (Fig.
4); however,
the culture of this tissue
yielded no growth. Because of the radiological
and histopathologic
findings the dosage of LAMB was increased
to 10 mg/kg/day and
itraconazole (ITRA), 7.5 mg/kg/day, was added
and increased to 7.5 mg/kg every 12 h according to levels in serum.
The patient also
received granulocyte colony-stimulating factor,
5 µg/kg/day, as
adjunctive therapy. Clinical and radiological
improvement occurred
after the LAMB dose was increased and ITRA
was added. This combination
was continued for 8 months, following
which LAMB was discontinued and
ITRA was continued as suppressive
therapy. Repeated CT of the chest and
brain 3 months after LAMB
was discontinued showed no progression of the
lesions. The child
currently remains stable on ITRA, 15 mg/kg/day, with
concomitant
reduction in size of the brain abscess and resolution of
the lung
nodules.
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FIG. 4.
Lung biopsy. (A) Cavitary lesion in the right lobe; (B)
hematoxylin and eosin stain showing necrotizing cavitating pneumonia.
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Histopathology.
The specimen from the brain aspirate consisted
of multiple tiny pieces of grayish soft and necrotic white tissue. The
frozen section showed necrotic brain tissue with granulomatous
inflammation suggestive of fungal infection. GMS stain revealed
numerous branching septate hyphae (Fig. 3). The lung biopsy consisted
of a central rounded irregular cavity measuring 3 cm in diameter filled
with creamy gray solid mass separated from the surrounding tissue (Fig. 4A). The microscopic findings were consistent with necrotizing cavitating invasive fungal pneumonia (Fig. 4B). The GMS stain demonstrated multiple hyphal elements similar to those in the brain.
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MATERIALS AND METHODS |
Mycology.
The aspirate of the brain abscess and the lung
biopsy were plated on Sabouraud dextrose agar (SDA) and brain heart
infusion agar. No organisms grew from lung biopsy. The brain abscess
aspirate yielded several colonies of a mold that was identified
initially as a Paecilomyces species based on its formation
of conidia in short chains. The isolate was referred to the Fungus
Testing Laboratory, Department of Pathology, University of Texas Health
Science Center at San Antonio for further identification and
susceptibility testing. There, the isolate was examined on potato
flakes agar (PFA) prepared in-house and incubated at room temperature
in ambient air with alternating daylight and darkness. Based on its
colonial and microscopic features, the fungus was identified as
A. fusispora and given accession number UTHSC 98-2508. The
isolate was subsequently referred to the University of Alberta
Microfungus Collection and Herbarium, Edmonton, Alberta, Canada,
accession number UAMH 9508, for comparison with six other isolates of
this species (Table 1) (23).
Cultural and microscopic features were examined on SDA, PFA, and potato dextrose agar (Difco Laboratories, Detroit, Mich.) plates incubated at
30 and 37°C. Terms for colony colors are according to Kornerup and
Wanscher (14). PFA slant cultures were evaluated for growth at 25, 35, and 42°C. The case isolate (UTMB 3307 = UTHSC
R-3122 = UAMH 9684) from a dog with systemic mycosis (Welsh,
personal communication) was acquired later and included in some
comparative analyses (Table 1).
Scanning electron microscopy.
Stubs were mounted with
Spot-O-Glue labels (Avery, Diamond Bar, Calif.) and touched to the
fungal culture. Preps were coated with gold-palladium using a Balzers
MED 010 vacuum evaporator (Technotrade International, Inc., Manchester,
N.H.) and examined with a JEOL (Tokyo, Japan) 840A microscope.
Antifungal susceptibility testing.
The case isolate and six
additional strains (Table 2) were tested
in a broth macrodilution method using NCCLS reference standard M27-T or
M27-A (16, 17) modified for filamentous fungi to determine
their susceptibility to antifungal agents. Isolates were grown on PFA
slants at 25°C for approximately 1 week. Mycelium was flooded with
sterile distilled water and scraped to obtain a conidial suspension.
The case isolate was tested in 1999 utilizing M27-A in which conidial
suspensions were standardized by hemacytometer conidial counts, with a
final inoculum concentration of 1.0 × 104 CFU/ml.
Isolates 96-2378 and R-2940 through R-2944 were tested in 1997 utilizing M27-T in which the suspension was standardized spectrophotometrically at 95%T at 530 nm and then diluted 1:10 to
provide a final inoculum concentration of 1.0 × 104
CFU/ml.
Antifungal agents and ranges tested included AMB (E. R. Squibb & Sons, Princeton, N.J.), 0.03 to 16 µg/ml; 5-fluorocytosine
(5-FC)
(Roche Laboratories, Nutley, N.J.), 0.125 to 64 µg/ml;
fluconazole
(FLU) (Pfizer, Inc., New York, N.Y.), 0.125 to 64
µg/ml; ITRA
(Janssen Pharmaceutica, Titusville, N.J.), 0.03 to
16 µg/ml; and
miconazole (MON), 0.03 to 16 µg/ml. Tubes were incubated
at 35°C
and read at 24 and 48 h. MICs were defined based on the
first tube
with a score of 0 (optically clear) for AMB and a score
of 2 (a
reduction of 80% or more in turbidity as contrasted with
the drug-free
control tube) for the other agents tested. Minimum
lethal
concentrations (MLCs) were determined for AMB by plating
100 µl of
the 24-h growth from the drug-free control tube, the
MIC tube, and each
tube with a concentration above the MIC onto
an SDA plate. The MLCs,
read at both 24 and 48 h, were defined
as the lowest concentration of
antifungal compound resulting in
five or fewer colonies on the SDA
plate. The
Paecilomyces quality
control strain UTHSC 90-459, which has known values, was run in
conjunction with the test isolates
in all antifungal susceptibility
testing.
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RESULTS |
Features of case isolate UTHSC 98-2508.
After 10 days of
incubation at 30°C, colonies appeared white to buff with darker
concentric circles on SDA and were a darker gray-brown on PFA. The
reverse of colonies was brownish with centrally darker areas on SDA and
a solid gray-brown on PFA. Basally inflated phialides (6 to 10 µm
long by 3.5 to 6 µm wide) occurred along the sides of thin-walled,
hyaline-to-pale brown septate hyphae (1.5 to 3.5 µm in diameter)
(Fig. 5A) and on long, unbranched brown
echinulate conidiophores (3 to 4 µm wide) that tapered at the tip.
The phialides, sometimes proliferating, occurred singly or in pairs and
occasionally in whorls (Fig. 5B). They bore long chains of
limoniform-to-fusiform, one-celled, smooth, hyaline conidia (4.5 to 6.5 µm by 2.5 to 3.5 µm) (Fig. 5C). The echinulate brown conidiophores
were prostrate on the subhyaline (very slightly pigmented) vegetative
mycelium and were sometimes anchored by a definite basal hyphal cell
(Fig. 5D), and they bore phialides sparingly along the sides and near
the apex (Fig. 5E). Temperature studies on PFA revealed rapid growth at
both 35 and 42°C.
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FIG. 5.
Microscopic morphology. (A) Basally inflated phialides
of case isolate, UTHSC 99-2508, occurring along the sides of
thin-walled, hyaline-to-pale brown septate hyphae (magnification,
×306). (B) Proliferating phialides of the case isolate, UTHSC 99-2508 (magnification, ×306). (C) Long chains of limoniform-to-fusiform,
one-celled, smooth, hyaline conidia of the case isolate, UTHSC 99-2508 (magnification, ×613). (D) Echinulate, brown, prostrate conidiophore
of isolate UTHSC 96-2378, anchored by a definite basal hyphal cell
(magnification, ×580). (E) Basally inflated phialides of dog isolate
R-3122, borne along the sides of brown, echinulate conidiophores
(magnification, ×306).
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Comparison with other isolates.
The isolates identified as
A. fusispora varied in growth rates and colonial features
(Table 1). All grew faster at 37°C (colony diameters, 5 to 8 cm after
7 days) (Table 1) than at 30°C (diameter 3.1 to 5.2 cm). Colonies of
the case isolate (UTHSC 98-2508) (Fig. 6A) and isolates R2942, R2940, and R2943
were similar in being predominantly light orange with patches of pale
gray on the top side and yellow to brownish orange, grayish brown, or
uniformly brownish black on the reverse (Table 1). The other isolates
were darker gray to brownish gray on the obverse and reverse (Fig. 6B).
All produced dark, echinulate conidiophores, but none displayed the
complex whorls of phialides borne at the tips as is usually depicted
for the species (6, 13, 20). More commonly, phialides occurred singly and in pairs along the length of the conidiophore or on
the vegetative hyphae. The brown conidiophores were prominant in
isolates with darker colonies but developed in all isolates in older
cultures and on media such as PFA. Sometimes they arose from
sclerotium-like structures (round aggregations of hyphae). Conidial
size and ornamentation varied among the isolates (Table 1). Walls were
smooth or very slightly roughened (case isolate, 96-2378 and R-2942
[Fig. 7A]) to finely echinulate (R-2944
[Fig. 7B]) or coarsely echinulate in spiral bands (R-2940, R-2941,
and R-2943 [Fig. 7C]) (Table 1). Conidium dimensions fell within a
range of 4 to 9 µm long by 2 to 6 µm wide, with R-2943 having the
largest dimensions. The conidia of the case isolate and R-2941 (dog)
were similar in size, but they differed in color and ornamentation. Our
observations were similar to those of Brown and Smith (4) for both microscopic features and growth habit. They had noted that
isolates grew rapidly within 7 to 10 days but that by 21 days, colonies
rarely reached the edge of the petri dish. Although some of our
isolates did attain diameters of 100 mm within 15 days at 37°C, the
average hourly growth rate after 3 days at 37°C was 0.46 mm/h,
compared with 0.38 mm/h after 7 days (0.33 and 0.25 mm/h, respectively,
at 30°C).
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FIG. 6.
Colonial morphology after 7 days of incubation on PDA at
37°C. (A) Colony of the case isolate, UTHSC 99-2508; (B) colony of
dog isolate R-3122.
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FIG. 7.
Electron microscopy. (A) Scanning electron micrograph of
smooth-to-slightly roughened conidia, soil isolate R-2942
(magnification, ×10,000). (B) Scanning electron micrograph of conidia
with fine spirals, from human corneal isolate R-2944 (magnification,
×10,000). (C) Scanning electron micrograph of conidia with coarse
spirals, from human bronchial washing isolate R-2943 (magnification,
×10,000).
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Antifungal susceptibility.
The MICs of AMB against isolates of
A. fusispora ranged between 0.25 and 2.0 µg/ml, and the
MLCs ranged from 1.0 to 16 µg/ml (Table 2). These concentrations are
within or above the safely achievable levels in plasma. Human isolates
had lower 48-h MLCs of AMB than did nonhuman isolates, suggesting cidal
activity at generally achievable drug levels. The isolates were
inhibited by relatively low concentrations of ITRA and MON, but only by relatively high concentrations of FLU, demonstrating dose-dependent susceptibility (a term employed to indicate susceptibility of an
organism at escalated doses of the drug). All isolates were resistant
to high concentrations of 5-FC.
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DISCUSSION |
Other cases.
A. fusispora is a thermotolerant
fungus with a wide distribution in tropical and temperate regions.
Although this fungus has been regarded as suspicious for potential
pathogenicity due to its isolation from eye and lung specimens (Table
1) (23), data have been insufficient to establish etiology.
There is only one confirmed report concerning an eye infection, in a
patient from India, and in that case, the authors were able to induce
keratitis experimentally in rabbits by using the organism recovered
from the patient (22). A. fusispora, originally
placed in the genus Paecilomyces, is seldom described in
medical mycology texts (5, 24), raising the question as to
whether lack of information on this fungus has led to its being
misidentified or overlooked as a potential pathogen. We have determined
that one case published under the name S. chartarum involves
this fungus. Welsh (personal communication) described systemic
infection with brain involvement in a stray dog captured in Edmond,
Okla. Their isolate is reidentified here as A. fusispora
(UTMB 3307 = UTHSC R-3122 = UAMH 9684 [Table 1]).
Coincidentally, UAMH 4425, acquired in 1981, was isolated from heart
and brain tissue of a dog from Stillwater, Okla. Although no further
details are available concerning the second dog, R. D. Welsh
(personal communication) has confirmed that these are two separate
cases. Ours is the first case of human cerebral infection and
demonstrates that A. fusispora is another dark fungus
potentially able to cause brain infection (2, 25). However
it should be noted that isolates of A. fusispora vary in
pigmentation and are not uniformly dark, as demonstrated by our
patient's isolate (Table 1).
Present case.
Our patient demonstrated clinical and
radiological response only to combination therapy with high-dose LAMB
and ITRA. The pneumonia in this case was most likely caused by the same
pathogen, which failed to grow due to the prolonged antifungal therapy
prior to the time of the lung biopsy. Brain abscesses caused by molds can be very difficult to treat and often have a fatal outcome. The
clinical manifestations (seizures, pneumonia) and risk factors (history
of neutropenia and corticosteroids) of CNS Acrophialophora infection, in this case, are very similar to those of CNS aspergillosis (28). Hagensee et al. (11) found a 97% mortality
rate in a review of the records of 58 patients with brain abscess
following bone marrow transplant for treatment of hematologic
conditions such as leukemia and aplastic anemia. Fungi, mainly
Aspergillus and Candida species, were isolated in
92% of cases. A Scopulariopsis species was identified as
the etiologic agent in one of these cases. As noted above, the
disseminated infection in the dog was also attributed to a species of
Scopulariopsis (29). Baddley et al.
(2), when reporting the dematiaceous ascomycete
Microascus cinereus (anamorph Scopulariopsis) as
the cause of brain abscess in a bone marrow transplant recipient,
pointed out that careful examination is required to discriminate the
conidial stage from the superficially similar genus
Paecilomyces.
Susceptibility and therapy.
Although standardization of
antifungal susceptibility testing for filamentous fungi is only
commencing (9) and breakpoints for Candida do not
apply (19), some assessment as to an isolate's in vitro
susceptibility can be inferred by comparing normally achievable
concentrations of the antifungal agents in serum in patients receiving
the recommended dosages (10, 21) with the MICs or MLCs for
the isolate. Utilizing this approach showed that all isolates appeared
susceptible to ITRA and MON. Isolates also appeared susceptible to AMB
based on MICs (Table 2), except R-2942, for which the 48-h
MIC was 2 µg/ml. Curiously, most human isolates appeared susceptible
to AMB based on MLCs, excluding 96-2378, while nonhuman (one animal and
two soil) isolates appeared resistant. Although the isolates
displayed dose-dependent susceptibility to FLU, this agent is generally
less efficacious for opportunistic filamentous fungi.
The MIC of AMB for the index isolate was 1.0 µg/ml, which is near the
higher range of the maximum safely achievable peak concentrations
of
this polyene in plasma. The patient's infection progressed
despite a
high dosage of AMB (1 mg/kg/day). Thus, the MIC of 1
µg/ml in this
patient correlates with a response observed only
at the highest dose
range of amphotericin. ITRA also may have
contributed substantially to
treatment of this patient's infections
and was instituted in order to
provide a compound that achieved
high concentrations in brain tissue
(
10). That the MICs and
MLCs of AMB against other isolates
of
A. fusispora are relatively
high suggests that therapy in
immunocompromised patients may fail
despite administration of
conventional AMB or lipid formulation
of AMB. The addition of high-dose
ITRA (
21) with documentation
of therapeutic plasma
concentrations above its MIC may have an
important role in management
of disseminated infections due to
this new human
pathogen.
Taxonomy.
The genus Acrophialophora was described
by Edward in 1959 with the type species A. nainiana for a
fungus that was repeatedly recovered from Indian soil during the warmer
months (7). The fungus was considered similar to
Paecilomyces in forming chains of ellipsoidal to fusiform
conidia from basally swollen phialides that were borne either on
conidiophores or directly from the vegetative hyphae. However, the
organism manifested several striking differences that included (i)
unbranched, erect, brown, echinulate conidiophores that were fertile
only near the apex; (ii) a basal, hyphal cell anchoring the
conidiophore to the vegetative hyphae, somewhat like a foot cell in the
genus Aspergillus; (iii) a distinct swelling at the base of
the phialides; and (iv) phialides that did not curve or bend away from
the main axis. Barron (3) did not accept the genus as being
different from Paecilomyces, but Ellis (8) accepted it as distinct and listed A. fusispora as the type
species based on an earlier published name (Paecilomyces
fusisporus Saksena 1953). Ellis regarded A. nainiana
Edward as a synonym of A. fusispora; however, he was
apparently unaware of the redescription of Acrophialophora by Samson and Mahmood (20) that appeared about the same
time. These authors compared 13 strains mostly isolated from the soil and recognized three species. They were differentiated mainly by
conidial ornamentation and the degree of development of brown conidia
but showed overlapping conidial dimensions: A. nainiana, with mature conidia that were hyaline and finely echinulate (measuring 4 to 10.5 µm long and 2 to 5 µm wide); A. fusispora
(Saksena) Samson, with mature conidia brown, thick walled, and with
echinulations in spiral bands (measuring 5 to 12 µm long and 3 to 6 µm wide); and A. levis Samson et T. Mahmood, with mature
conidia smooth to slightly roughened and hyaline (measuring 4.5 to 8 µm long and 2 to 3.5 µm wide).
Although the case isolate could fit the description of
A. levis following the species concepts proposed by Samson and
Mahmood,
we take the broader view that
A. fusispora includes
a continuum
of conidial roughness from smooth to distinctly spiraled.
This
broad concept is supported by other common and overlapping
characteristics,
including thermotolerance, growth rates, colonial
pigmentation,
conidial dimensions, and in vitro susceptibility data.
Although
the four human isolates demonstrated lower MLCs of AMB (Table
2), these same isolates demonstrated variability in growth rates,
colony color, and conidial wall ornamentation and size (Table
1).
Based on this broad species concept, the case isolate and other
isolates are identified as
A. fusispora. Features
identifying
the species include the following. (i) Isolates are
thermotolerant,
showing good growth at 42°C or higher. (ii) Colonies
are initially
buff or tan, usually becoming grayish brown with an
uncolored
or dark grayish brown reverse. Note that colonies of the case
isolate remained lighter colored. (iii) Basally swollen phialides
are
borne mostly singly on the vegetative hyphae or along the
length and
near the tip of brown, echinulate conidiophores. (iv)
Limoniform-to-fusiform or ellipsoidal conidia are borne in long
chains
and are smooth or finely to coarsely echinulate, sometimes
in spiral
bands. (v) Phialides do not curve away from the main
axis. (vi)
Phialides sometimes proliferate to form a second opening
(Fig.
5B).
Phialides producing more than one opening not delimited
by a septum are
also referred to as polyphialides. This recently
recognized fungal
pathogen differs from
Paecilomyces in having
colonies that
turn dark and in forming brown echinulate conidiophores
and differs
from
Scopulariopsis species in forming conidia from
phialides rather than
annellides.
As demonstrated by the present case,
A. fusispora is capable
of causing a devastating cerebral infection in a human, thus
requiring
aggressive antifungal therapy. This fungus has the potential
to be
neurotropic, as evidenced by our case and two cases involving
dogs.
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FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Pediatrics, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Phone: 966 1 442 7762. Fax: 966 1 442 7784. E-mail: imohsen{at}kfshrc.edu.sa or
ialmohsen{at}hotmail.com.
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Journal of Clinical Microbiology, December 2000, p. 4569-4576, Vol. 38, No. 12
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Abstract
Introduction
