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Brief Reports
munoassay, mouse bioassay and in vitro guinea pig atrium assay. Toxicon
6. Hokama Y. Simplified solid-phase immunobead assay for detection of ciguatoxin and related polyetbers. J Clin Lab Anal 1990;4:213-7.
7. Food and Drug Administration. Defect action levels for histamine in tuna:
availability of guide. Fed Regist 1982;470:40487.
1996;23 (December)
8. Y oshinaga DH, Frank HA. Histamine-producing bacteria in decomposing
skipjack tuna (Katsuwonus pe/amis). Appl Environ MicrobioI1982;44:
9. Clifford MN, Walker R, Ijomah P, Wright J, Murray CK, Hardy R. Is tbere
a role for amines otber than histamines in the aetiology of scombrotoxicosis? Food Addit Contam 1991;8:641-52.
Aspergillus Meningitis in an Immunocompetent Adult
Successfully Treated with Itraconazole
Aspergillus fumigatus meningitis is rare. It typically occurs in
immunocompromised hosts, has a fatal outcome, and is diagnosed
at autopsy. We present the first known case of A. fumigatus meningitis in an immunocompetent patient who was cured by treatment
with itraconazole.
A 25-year-old woman from the Dominican Republic was evaluated for a progressively worsening headache of3 months' duration
and vomiting and photophobia of 1 month's duration. CT brain
scans without contrast obtained 1 month before and on admission
to the hospital did not show any abnormalities. The patient had
no identifiable risk factors for infectious diseases.
Physical examination on admission was normal except for bilateral grade III papilledema. Lumbar puncture revealed an opening
CSF pressure of 430 mm H2 0. Laboratory studies of the CSF
showed the following values: glucose, 40 mg/mdL; protein, 92
mg/dL; 200 WBCs (2% neutrophils); and 2 RBCs. A gram stain,
an India ink stain, and a stain for acid-fast bacilli were negative, as
was a test for cryptococcal antigen. Findings on a chest radiograph,
results of urinalysis and routine blood studies, and the erythrocyte
sedimentation rate were all normal; cultures of blood, CSF, and
urine were negative. A gadolinium-enhanced MRI revealed an
enhancing lesion that encased the basilar artery from the prepontine
cistern to the interpeduncular fossa.
Although a tuberculin test with PPD was negative, a presumptive
diagnosis of tuberculosis was made, and treatment with streptomycin, pyrazinamide, isoniazid, and rifampin was given daily, starting
on the 11th hospital day. Despite this treatment, fundus hemorrhages developed. Sinus radiographs showed a I-cm osteoma in a
maxillary sinus. Findings on a bone window CT scan of the clivus
were normal. Findings on a gallium scan were normal 24, 48, and
72 hours after administration of the radioisotope.
Lumbar punctures were performed several times; cytologies,
cultures, and stains of CSF were always negative. A gadoliniumenhanced MRI obtained on the 25th hospital day revealed an
enhancing extra-axial mass extending along the brain stem
(figure 1).
Four weeks after admission, the patient still appeared healthy.
She underwent a left subtemporal craniotomy, and thick, gelatinous
Reprints or correspondence: Dr. Dennis Mikolich, Division of Infectious
Diseases, Veterans Affairs Medical Center, 830 Chalkestone Avenue, Providence, Rhode Island 02908-4799.
Clinical Infectious Diseases 1996; 23:1318-9
© 1996 by The University of Chicago. All rights reserved.
1058-4838/96/2306-0041 $02.00
Figure 1. Prebiopsy coronal gadolinium-enhanced MRI of the
brain of a patient with aspergillus meningitis; an enhancing meningitic
process extends along both medial temporal lobes.
exudate was found. Gomori's methenamine-silver stain revealed
hyphae with acute-angle branching. Anaerobic culture yielded
large colonies of A. fumigatus within 3 days.
She was initially treated with itraconazole (800 mg daily). This
dose was lowered to 400 mg daily as the results of CSF tests
began to normalize. These results slowly returned to normal over
5 months. Serum levels of itraconazole, determined by bioassay
~2.5 hours after dosing, ranged between 3.2 mg/mL and 18.0
mg/mL. She was treated with itraconazole for 24 months and
observed for an additional 2 years, without evidence of a neurological deficit or any medical problem.
Itraconazole has proved to be an effective alternative to amphotericin B in the treatment of patients with various manifestations
of aspergillosis and other mycotic infections [1-4]. CNS aspergil-
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1996;23 (December)
Brief Reports
losis is an opportunistic fungal infection that usually affects immunocompromised hosts [5]. Treatment has been unavailing, largely
because of the patient's underlying diseases; treatment failure possibly may be related to poor response to antifungal drugs.
Aspergillus species are extremely difficult to cultivate in cultures
of antemortem specimens [6]. Young et al. [7] found that 34% of
antemortem specimens were positive for Aspergillus; however,
Bodey [6] did not identify Aspergillus in any antemortem cultures
of specimens from 454 patients with acute leukemia complicated
by fungal infections.
The route of infection in our patient remains speculative. Tests
for antibodies to HIV were negative on four occasions over a 2year period. Her WBC count and T cell subset counts remain
normal, and she has had no other immunocompromising illnesses.
The initial high dose of itraconazole was required for our patient
to achieve detectable blood levels of the drug because she had
been taking rifampin. However, itraconazole was not detectable
in serum until 4 weeks after discontinuation of rifampin therapy.
Rifampin is known to induce hepatic enzymes that degrade itraconazole [8], and the patient stopped receiving the antituberculous
medications once the correct diagnosis had been established.
Despite its negligible penetration into human CSF [8], itraconazole has been effective as the sole therapy for certain fungal meningitides such as coccidioidal and cryptococcal meningitis [1, 8, 9].
By using this oral agent, we avoided the prolonged hospitalization
often needed to administer intravenous amphotericin B and the
placement of an Ommaya reservoir for administration of intrathecal amphotericin B. In this case, the result has been extremely
Given the location of our patient's lesion and the risks of a brain
biopsy, we undertook an extensive and lengthy evaluation in an
attempt to avoid performing a biopsy. Her presentation demonstrates the need to identify an etiologic agent of meningitis when
cultures are negative. The findings in this case once again underscore the importance of establishing the diagnosis histopathologically for choosing the most appropriate therapy. We believe that
itraconazole may represent a major advance in the treatment of
A. fumigatus meningitis. However, specific recommendations regarding dosage and duration of therapy have not been established
and may be difficult to formulate given the rarity of this infection.
Invasive Sinusitis Due to Sporothrix schenckii in a Patient
with AIDS
A 49-year-old homosexual man with AIDS was referred for
otolaryngological evaluation; he had a 3-month history of persistent maxillary sinus pain and bloody nasal discharge. His symptoms had not abated after several courses of empirical antibiotics
for treatment of sinusitis. An initial CT scan of the sinuses showed
only mild right maxillary mucosal thickening. After 1 month of
treatment with normal saline nasal washes and steroid nasal spray,
he retumed to the hospital with progressive symptoms and swelling
of the right nasal bridge. He denied headache, skin lesions, or
systemic symptoms.
His medical history was significant for an episode of pneumocystis pneumonia and localized herpes zoster that resolved with
treatment; a recent CD4+ cell count was 19/mm3 . He had undergone surgery for a deviated septum in the distant past and had
experienced periodic episodes of sinusitis. He was receiving trimethoprim-sulfamethoxazole daily as prophylaxis for pneumocystosis. He had no significant history of exposure except for
gardening-he maintained several hundred orchids, succulents,
and cacti in his house. Recognizing the risk for sporotrichosis, he
wore gloves whenever he handled sphagnum moss, which is used
in potting soil.
Sporothrix schenckii is a dimorphic fungus with worldwide distribution; this fungus classically causes localized infection at the
site of inoculation, followed by satellite lesions that slowly spread
proximally along lymphatic pathways [1]. Case reports ofsporotrichosis associated with AIDS reveal a range of clinical disease,
including more invasive and widely disseminated disease. We report a case of invasive sinusitis due to sporotrichosis in a patient
with AIDS; the sinusitis was successfully treated with itraconazole.
Reprints or correspondence: Dr. Myra Morgan, Box B-168, University of
Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, Colorado
Clinical Infectious Diseases 1996; 23:1319-20
© 1996 by The University of Chicago. All rights reserved.
Dennis J. Mikolich, L. J. Kinsella, Gail Skowron,
Joseph Friedman, and Alan M. Sugar
Divisions of Infectious Diseases and Neurology, Roger Williams Medical
Center, Division of Infectious Diseases, the Department of Veterans
Affairs Medical Center, and Department of Medicine, Brown University
School of Medicine, Providence, Rhode Island; and the Department of
Medicine, The University Hospital, Boston, Massachusetts
1. Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern
Med 1989;149:2301-8.
2. Denning DW, Tucker RM, Hanson LH, Stevens DA. Treatment of invasive
aspergillosis with itraconazole. Am J Med 1989;86:791-800.
3. Denning DW, Tucker RM, Hanson LH, Stevens DA. Itraconazole in opportunistic mycoses: cryptococcosis and aspergillosis. JAm Acad Dermatol
4. Viviani MA, Tortorano AM, Langer M, Almaviva M, Negri C, Christina
S. Experience with itraconazole in cryptococcus and aspergillosis. J Infect
Dis 1989; 18:151-65.
5. Salaki JS, Louria DB, Chmel H. Fungal and yeast infections of the central
nervous system: a clinical review. Medicine (Baltimore) 1984;63:10832.
6. Bodey GP. Fungal Infections complicating acute leukemia. J Chronic Dis
1966; 19:667-87.
7. Young RC, Bennett JE, Vogel CL, Carbone PP, DeVita VT. Aspergillosis,
the spectrum of disease in 98 patients. Medicine (Baltimore) 1970;49:
8. Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy
for chronic coccididioidal meningitis. Ann Intern Med 1990; 112: 10812.
9. Denning DW, Lee JY, Hostetler JS, et al. NIAID Mycoses Study Group
multicenter trial of oral itraconazole therapy for invasive aspergillosis.
Am J Med 1994;97:135-44.