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Case report

Lethal otogenic Candida meningitis

Fallbericht. Letale otogene Candida-Meningitis

S. Koch,1 B. Rudel1 and H.-J. Tietz2
Institut für Pathologie, Humaine Klinikum Bad Saarow, Akademisches Lehrkrankenhaus der Freien Universität Berlin and 2Klinik für Dermatologie, Venerologie
und Allergologie, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität, Campus Charité Mitte, Berlin, Germany

Summary A 61-year-old woman with clinical signs of meningitis/encephalitis was admitted to

hospital in a somnolent state. Inquiries with regard to the history revealed a chronic
obstructive pulmonary condition which had been treated with prednisolone for a long
time. There was a raised temperature with further signs of an acute inflammatory
underlying disease and internal hydrocephalus. After performing trepanation, the
symptoms of raised intercerebral pressure ceased. Candida albicans could be detected
microbiologically in the cerebrospinal fluid. There was no pneumonia at the time of
admission. Despite instituting immediate intensive care with administration of antibiotics
and antimycotics, the patient died 11 days after inpatient admission. Autopsy revealed a
C. albicans mycosis originating from the right middle ear with extensive suppurative
meningitis, which was the immediate cause of death. Confluent bronchopneumonia had
developed in both lower lung lobes at the time of death, but did not show any signs of
mycosis and had contributed indirectly to the death of the patient.

Zusammenfassung Eine 61jährige Frau wurde mit klinischen Zeichen einer Meningitis/Enzephalitis in
somnolentem Zustand stationär aufgenommen. Anamnestisch war eine chronisch-
obstruktive Lungenerkrankung eruierbar, die langzeitig mit Prednisolon behandelt wurde.
Es bestanden eine erhöhte Körpertemperatur, weitere Zeichen einer akuten entzündlichen
Grunderkrankung und ein Hydrocephalus internus. Nach erfolgter Bohrlochtrepanation
sistierte die Hirndrucksymptomatik, wobei mikrobiologisch ein Nachweis von Candida
albicans im Liquor cerebrospinalis gelang. Zum Aufnahmezeitpunkt lag keine Pneumonie
vor. Trotz sofort einsetzender intensivmedizinischer Therapie mit Applikation
antibiotischer und antimykotischer Substanzen trat 11 Tage nach stationärer
Aufnahme der Exitus letalis ein. Die Obduktion ergab eine vom rechten Mittelohr
ausgehende Candida albicans-Mykose mit ausgedehnter eitriger Meningitis, die die
unmittelbare Todesursache darstellte. Eine konfluierende Bronchopneumonie, die sich
zum Todeszeitpunkt in beiden Lungenunterlappen ausgeprägt hatte, bot keine Zeichen
einer Mykose und hat mittelbar zum Todeseintritt beigetragen.

Key words: candidosis, otomycosis, meningitis, autopsy.

Schlüsselwörter: Candidose, otomykose, meningitis, autopsie.

Case report
Correspondence: PD Dr Stefan Koch, Institut für Pathologie, Humaine
Klinikum Bad Saarow, Akademisches Lehrkrankenhaus der Freien Universi- A 61-year-old woman was referred for inpatient admis-
tät Berlin, Pieskower Straße 33, D-15526 Bad Saarow, Germany.
sion by a doctor on emergency call. Raised body
Tel.: +49-33631-73210. Fax: +49-33631-73010.
temperatures of about 38 C had been measured for
several days. The patient was suffering from headache,
Accepted for publication 24 June 2003 general asthenia and difficulties in walking. We cannot

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Lethal otogenic Candida meningitis

establish the history on the basis of our own records.

Other records revealed chronic obstructive pulmonary
disease (COPD) and a chronic cor pulmonale. The constellation of clinical findings at the time of
At the time of inpatient admission, there was men- admission corresponds to the manifest meningitis that
ingitis, positive Kernig’s and Brudzinski’s signs, aniso- was indeed later confirmed morphologically by compu-
coria and a retarded reaction of the eyes to light stimuli, ter tomography and autopsy. Hypersecretion or a
poor coordination and general muscular weakness. The disorder of CSF resorption which had led to the
patient was awake and showed person-orientation. hydrocephalus internus was clearly associated with
Speech communication was not possible, which was meningitis. An investigation of the middle ear was not
why motor aphasia was also considered. The neurolog- undertaken at the time of admission. On inpatient
ical investigation suggested meningitis/encephalitis. admission, no indications of bronchopneumonia were
Cranial computer tomography revealed an internal found. Consequently, its occurrence is likely to be a
hydrocephalus with congestion of the ventricular sys- secondary disease phenomenon. Therefore, generaliza-
tem of the brain. External ventricular drainage was tion of a pre-existing Candida pneumonia with involve-
attained by setting up a drainage system. The micro- ment of the central nervous system (CNS) can be ruled
biological investigation of the cerebrospinal fluid (CSF) out. In the absence of signs of mycotic pneumonia or
revealed Candida albicans infection. In the blood culture, urocystitis, detection of Candida in the bronchial secre-
Candida antigens were not found but anti-Candida tion and in the urine is a manifestation of a general
antibodies were present (immunohemagglutination test, reduction in bodily resistance in which the effectiveness
1 : 160) (Central Laboratory of the Humaine Hospital of mucosal antimicrobial and antimycotic defense
Center in Bad Saarow). Candida albicans and Acineto- mechanisms is reduced in the episomatic biotopes.
bacter baumannii were detected in the bronchial secretion. However, it is also possible that antibiotic or
Culture of catheter urine contained 10 000 organisms antimycotic treatment instituted between the time of
per ml. Despite antibiotic treatment with rocephine, admission and autopsy (about 10 days) had eliminated
sulfamethoxazole; trimethoprim, fosfomycin, gentamy- a systemic candidosis with involvement of the paren-
cin and intensive-care treatment, the patient died with chymatous organs which had occurred in the inter-
clinical signs of sepsis 11 days after inpatient admission. vening period to the extent that it could no longer be
The patient was autopsied (A 20/2002) on the detected at the time of autopsy.
following day. The main finding was a basal suppurative The pathogenesis is likely to be otogenic. This putative
candida leptomeningitis with focal incipient diffuse diagnosis is also corroborated by the predominantly
yellow–green coating in the region of the temporal basal localization of the inflammation, which had
lobes bilaterally, the pons, medulla oblongata and evidently spread per continuitatem. In general, hemato-
cerebellum (Figs 1 and 2). Histological examination genous dissemination is found in systemic candidoses.
of the meninges showed a massive blastomycete coloni- Evidently, such a hematogenic dissemination occurred
zation with granulocytic and round-cell reaction only a short time before death in the present case.
(Figs 3–5) that had become granulomatous in places. Otomycosis is evidently not a rare disease or a condition
Moreover, with a brain mass of 1250 g, there was diffuse mainly occurring in children. In a study on 345 test
brain edema with applanation of the gyri and narrowing subjects (381 ears), otomycosis was found in 116
of the sulci as well as the normal fresher state after right patients (30.4%) with symptoms of otitis. This otomy-
frontal trepanation via which the ventricular drainage cosis was caused by Candida spp. in about 60% and by
was set up. The right middle ear showed a suppurative Aspergillus species in only 40%.1 The same authors
inflammation. Abundant C. albicans was found in assume that local lesions provide favorable conditions for
the smear from the ear and occasional C. albicans could fungal growth and the development of mycoses in the
be detected in the smear from the meninges. The external auditory meatus and in the middle ear.
contralateral middle ear was sterile (Central Laboratory Patients with hematologic neoplasias, solid tumors or
of the Humaine Hospital Center in Bad Saarow). immunosuppression resulting from other diseases (e.g.
Furthermore, there was general arteriosclerosis, the HIV infections) or corresponding medication 2 have a
clinically known COPD, confluent bronchopneumonia predilection to suffer from systemic mycoses. In the
on both lower lung lobes (negative fungal test) and present case, a chronic prednisolone medication of
peripheral thrombemboli in the lungs. Otogenic supp- about 2 mg per day was administered to treat the COPD.
urative C. albicans meningitis on the right side was About 25% of the endomycoses diagnosed in the
detected as the immediate cause of death. autopsy material also/or exclusively affect the CNS.3

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S. Koch et al.

Figure 3 Hyphae and blastoconidia of Candida within necrotic

meningeal tissue. Hematoxylin–eosin staining. ·120.

Figure 1 Underside of the brain (overview). Yellow film of pus in

the area of pons, medulla oblongata and cerebellum.

Figure 4 Candida hyphae in necrotic meningeal tissue. Grocott–

Gomori methenamine silver staining. ·120.

Figure 2 Underside of the brain, see Fig. 1. Cerebellum, pons,

medulla oblongata with greasy films of pus.

Whereas involvement of the CNS is observed in 80% of

cryptococcoses, this is the case in between 2 and 5% of
patients with candidosis.4 Compared with mycoses
caused by other fungal genera, candidosis of the CNS
Figure 5 Marginal region of the partly abscess forming and partly
is the most frequent mycotic infection. However, the granulomatous inflammation. Granulocyte-rich necrosis (left),
pertinent literature mostly refers to a study in which some histiocytic giant cells (right). Hematoxylin-eosin staining.
only 19 cases of CNS mycoses were considered.5 Since ·60.

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Lethal otogenic Candida meningitis

1958, the number of mycoses caused by Candida is pass the blood–CSF barrier. However, the prognosis is
reported to have almost doubled.6 Amongst 3770 brain still unfavorable for patients with Candida macroab-
autopsies performed in the investigation material from scesses.9
the Berlin Charité, there were 28 cases (0.74%) with
mycoses of the CNS comprising 39.3% candidoses,
35.7% aspergilloses, and 17.8% cryptococcoses. The
diagnosis was made whilst the patient was still alive in 1 Kurnatowski P, Filipiak A. Otomycosis: prevalence, clinical
only 6% of the cases.7 Evaluation of 4813 autopsies symptoms, therapeutic procedure. Mycoses 2001; 44:
carried out at the Bad Saarow Hospital Center (1973– 472–9.
2001) revealed involvement of the CNS and systemic 2 Luna MA, Tortoledo ME. Histologic identification and
pathologic patterns of disease caused by Candida. In: Bodey
mycoses in six cases (0.12%). Primary lethal mycoses
GP (ed.), Candidiasis: Pathogenesis, Diagnosis and Treatment.
did not occur in the specified period of investigation.8
New York: Raven Press, 1993: 21–42.
Macroscopically, involvement of the leptomeninx in 3 Gottschalk J, Wolter H, Vollert S. Zunahme der Endo-
candidosis resembles suppurative or tuberculous men- mykosen im Obduktionsgut?. Dt. Gesundh. wes. 1982; 37:
ingitis.4 However, reliable identification as candidosis is 1833–6.
possible in the case investigated, especially using the 4 Jänisch W, Schreiber D, Warzok R. Neuropathologie. Jena:
PAS reaction and the Grocott and Gomori silver stains. G. Fischer, 1990: S 163.
Besides meningitis, the histologic and morphologic 5 Parker JC, McCloskey JJ, Lee RS. Human cerebral candido-
spectrum of CNS candidiasis findings also comprises sis. A post mortem evaluation of 19 patients. Hum Pathol
microabscesses and macroabscesses, thrombosis and 1981; 12: 23–8.
aneurysms, development of solitary spherical fungal 6 Buchs S, Pfister P. Candida meningitis: course, prognosis,
and mortality before and after introduction of the new
masses, hemorrhages and hemorrhagic necroses, sub-
antimycotics. Mykosen 1982; 26: 73–81.
dural spinal granulomas and demyelinization.9 In the
7 Tietz H-J, Martin H, Koch S. Incidence of endomycoses in
case investigated, there was meningitis with suppura- autopsy material. Mycoses 2001; 44: 450–4.
tive inflammation of only slight extent as well as a hint 8 Koch S, Höhne F-M, Tietz H-J. Incidence of systemic
of granuloma formation with histiocytic giant cells mycoses in autopsy material. Mycoses 2004; 47: 40–46.
(Figs 3–5). 9 Moyer DV, Edwards JE. Candida ophthalmitis and CNS
The prognosis of patients with candidosis of the CNS infection. In: Bodey GP (ed.), Candidiasis: Pathogenesis,
has improved, especially after the introduction of new Diagnosis and Treatment. New York: Raven Press, 1993:
intravenously administrable antimycotics which can 346–55.

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