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Cladophialophora bantiana: A rare cause of fungal brain abscess. Clinical aspects and new therapeutic options

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Black molds or dematiaceous fungi are rare etiologic agents of intracerebral abscesses and such infections carry a high mortality of up to 70% despite combined surgical and antifungal therapy. While the growing use of immunosuppressive therapies and organ transplantation have caused an increase in the incidence of rare fungal cerebral infections, occurrence in immunocompetent hosts is also possible. We describe a 60-year-old female patient with a cerebral abscess caused by Cladophialophora bantiana. The case illustrates the clinical and radiological similarities between glioblastomas and brain abscesses and emphasizes the need to perform histological and microbiological studies prior to the initiation of any form of therapy. Long-term survival from cerebral black mold abscesses has been reported only when complete surgical resection was possible. The recommended antifungal treatment involves the use of amphotericin B combined with a triazole and, if possible, flucytosine. Highly-active new generation triazole antifungal compounds (voriconazole or posaconazole) are likely to offer improved survival rates for patients with rare mold infections. In particular, posaconazole could be a new therapeutic option given its better tolerance, lower toxicity and fewer drug-drug interactions. We discuss clinical, microbiological and practical pharmacological aspects and review current and evolving treatment options.
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Cladophialophora bantiana
: a rare cause of fungal brain
abscess. Clinical aspects and new therapeutic options
CHRISTIAN GARZONI*, LYDIA MARKHAM$, PHILIPPE BIJLENGA% & JORGE GARBINO$
*
Infectious Diseases Division, University Hospital of Bern, Bern,
$
Infectious Diseases Division, University Hospitals of Geneva,
Geneva, and
%
Neurosurgery, Department of Clinical Neurosciences, University Hospitals of Geneva, Geneva, Switzerland
Black molds or dematiaceous fungi are rare etiologic agents of intracerebral
abscesses and such infections carry a high mortality of up to 70% despite
combined surgical and antifungal therapy. While the growing use of immuno-
suppressive therapies and organ transplantation have caused an increase in the
incidence of rare fungal cerebral infections, occurrence in immunocompetent
hosts is also possible. We describe a 60-year-old female patient with a cerebral
abscess caused by Cladophialophora bantiana. The case illustrates the clinical and
radiological similarities between glioblastomas and brain abscesses and empha-
sizes the need to perform histological and microbiological studies prior to the
initiation of any form of therapy. Long-term survival from cerebral black mold
abscesses has been reported only when complete surgical resection was possible.
The recommended antifungal treatment involves the use of amphotericin B
combined with a triazole and, if possible, flucytosine. Highly-active new
generation triazole antifungal compounds (voriconazole or posaconazole) are
likely to offer improved survival rates for patients with rare mold infections. In
particular, posaconazole could be a new therapeutic option given its better
tolerance, lower toxicity and fewer drug-drug interactions. We discuss clinical,
microbiological and practical pharmacological aspects and review current and
evolving treatment options.
Keywords brain abscess, Cladophialophora bantiana, dematiaceous fungus,
posaconazole, voriconazole
Introduction
Cladophialophora bantiana is a highly neurotropic
dematiaceous fungus and a rare cause of cerebral
abscesses. Such infections carry a high mortality of
up to 70% and neurosurgical radical resection asso-
ciated with powerful antifungal treatment is the most
successful therapeutic strategy reported to date. We
describe a case involving a 60-year-old woman with an
unresectable C. bantiana brain abscess treated by a
combined approach of CT-guided aspiration and
aggressive antifungal therapy. Sequential imaging sug-
gests that the fungal infection was contained. This case
illustrates the absence of a pathognomonic image of
glioblastoma and the absolute need to obtain histo-
pathological confirmation when possible before initia-
tion of any treatment. Highly active new-generation
antifungal compounds will probably improve the
prognosis of rare mold infections of the central
nervous system (CNS) and we review the microbiolo-
gical and practical pharmacological aspects of these
evolving therapies.
Case Report
A 60-year-old woman was referred to our institution
because of fever and frequent falls ten days after her
arrival in the country. Upon admittance, she was sleepy
Correspondence: Jorge Garbino, Service of Infectious Disease,
University Hospitals of Geneva, 24 Rue Micheli-du-Crest, 1211
Geneva 14, Switzerland. Tel: 41 22 372 9839; Fax: 41 22 372
9832; E-mail: jorge.garbino@hcuge.ch
Received 4 September 2007; Accepted 14 January 2008
2008 ISHAM DOI: 10.1080/13693780801914906
Medical Mycology
August 2008, 46, 481486
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and confused. Her medical history included long-term
corticoid therapy (10 mg/d) and cholchicine 1 mg/d for
systemic sclerosis, pulmonary fibrosis and Raynaud’s
phenomenon which was in remission after six months
of cyclophosphamide treatment she received three years
earlier. She had chronic hepatitis C-related cirrhosis,
chronic thrombocytopenia linked to secondary hypers-
plenism (60 G/L, normal range 150350 G/L) and
arterial hypertension.
Neurological examination was normal apart from
drowsiness and confusion, as was the rest of the clinical
examination. Laboratory investigations revealed the
lack of an inflammatory syndrome (normal leucocytes,
C-reactive-protein B1 mg/l). Liver enzymes were
known to be chronically elevated because of active
hepatitis C. A cerebral CT-scan showed a 2 cm diameter
ring-enhancing lesion in the left posterior arm of the
internal capsule compressing the left lateral ventricle
(Fig. 1A & B). Magnetic resonance imaging (MRI) of
the brain showed a ring-enhancing lesion in the body of
the caudate infiltrating the corpus callosum and the
posterior arm of the internal capsule, strongly suggest-
ing the diagnosis of high grade glioma (Fig. 1C & D).
Due to the history of chronic immunosuppressive
therapy with prednisone and previous cyclophospha-
mide treatment for systemic sclerosis, the probability of
a secondary cerebral lymphoma or an opportunistic
infectious process was considered. Antibiotic treatment
with imipenem-cilastatin 500mg i.v. every 6 h associated
with dexamethasone 100 mg was started. Serology for
toxoplasma was negative (IgM and IgG) eliminating the
possible presence of a cerebral toxoplasmosis abscess.
The patient deteriorated during the first week
with the appearance of progressive right hemiparesis,
Fig. 1 Initial imaging of lesion. (A) Axial section of native CT-Scan demonstrating a discrete hypodensity in the left body of the caudate and
mass effect on the lateral ventricule. (B) Contrast-enhanced CT-Scan showing enhancement of the lesion. (C) Axial section of contrast-enhanced
T1-weighted MRI. (D) Coronal reconstruction of contrast-enhanced T1-weighted MRI showing extension within corpus callosum.
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aphasia and a worsening in sensorium. Notwithstand-
ing both the risk of hemorrhage increased by throm-
bocytopenia and radiological features advocating
glioblastoma diagnosis, a neuronavigation-guided fra-
meless needle biopsy was performed under platelet
transfusion. Approximately 5 ml of a total lesion
volume of approximately 67 ml was aspirated. Micro-
scopic analysis of Gram, Calcofluor white and Grocott
silver stained biopsy material revealed a brain abscess
suspected to be caused by a black mold.
The presumptive diagnosis was confirmed by further
analysis. The aspirated liquid was cultured onto
CHROMagar Candida (Beckton Dickinson, New Jer-
sey, USA). After 12 days, 20 mm size colonies were
noted developing in culture. They had a velvety texture
and were olive gray to black on the obverse and black
on the reverse. Microscopic examination of a lactophe-
nol stained slide culture preparation revealed brown
septate hyphae with long, sparsely branched conidio-
phores bearing wavy chains of smooth oval conidia.
The latter did not display dark attachment scars as has
been described for other Cladosporium spp. Aspirated
liquid was also inoculated onto Sabouraud dextrose
agar. The isolate recovered could grow at 428C, a
feature that differentiates C. bantiana from other
morphologically similar saprophytic fungi (Fig. 2). To
corroborate the identification of the species, samples
were subjected to a polymerase chain reaction (PCR)
amplification with ITS (internal transcribed spacer) 1
and ITS4 primers as previously described [1]. The
amplicon was sequenced on an ABI PRISM 310
Genetic Analyser sequencer (Applied Biosystems,
Rotkreuz, Switzerland); the resulting sequence was
analyzed with the FASTA program and compared
with other sequences of the Cladophialophora genus
published in GenBank (NCBI) and SeqWeb2.1.0. [1].
The results confirmed the microbiological diagnosis.
C. bantiana was susceptible to all antifungal agents
apart from fluconazole. The minimal inhibitory con-
centrations (MIC; YeastOne
TM
Trek Diagnostic, Penn-
sylvania, USA) obtained were (mg/ml): amphotericin
B, 1.0 mg/ml (susceptible S); fluconazole, 64 mg/ml
(resistant); itraconazole, 0.023 mg/ml (S); ketoconazole,
0.032 mg/ml (S); flucytosine, 1.0 mg/ml (S); voriconazole
0.064 mg/ml (S); posaconazole, 0.02 mg/ml (S); caspo-
fungin, 0.50 mg/ml (S). Since no breakpoints have been
well established for the different antifungal drugs, it is
difficult to establish a standardized antifungal therapy.
In addition, the efficacy of various antifungal agents
against black molds is not clearly defined in cases
involving humans. However, there has been limited
clinical experience with the newer antifungal com-
pounds like third-generation antifungal triazoles posa-
conazole and voriconazole.
Voriconazole (400 mg p.os b.i.d) and liposomal
amphotericin B (5 mg/kg body weight daily) were
started and gradually increased to 7 mg/kg/day. Vor-
iconazole was preferred over itraconazole because of
better bioavailability (96% vs 55%) and cerebrospinal
fluid penetration (90% vs. 50%). Flucytosine could not
be added to this regimen because of the risk of
myelotoxicity in a patient with chronic thrombocyto-
penia. Aphasia remained unchanged and right hemi-
plegia worsened. Brain MRI performed 5 days after
starting treatment showed an increase in the initial
lesion and new lesions following the biopsy tract (Fig.
3A). The increase in the levels of liver enzymes (ASAT
and ALAT) from 59 and 105 U/l at admission to 176
and 310 U/l, respectively (normal range, 1142 U/l))
confirmed hepatotoxicity and voriconazole was re-
placed by posaconazole (400 mg b.i.d p.os). Ten days
after the change to posaconazole, liver enzymes im-
proved rapidly (ASAT 115 U/l and ALAT 189 U/l).
A third MRI performed 11 days after the introduc-
tion of posaconazole showed control of the growing
brain abscesses. The volume of the lesions was sig-
nificantly reduced and less midline shift was evidenced
(Fig. 3B). Neurological deficits remained stable. Con-
sidering the dynamic of abscess growth before the
introduction of posaconazole, the findings were inter-
preted as evidence of the efficacy of the treatment with
posaconazole. Unfortunately, the patient developed
aspiration nosocomial pneumonia with severe sepsis
and died.
Fig. 2 Histological and cytological (inset) analysis (Grocott silver
stain coloration) revealed invasion of brain structures by septed low
branching hyphae.
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Discussion
Infection of the central nervous system caused by a
dermatiaceous mold is referred to as cerebral phaeo-
hyphomycosis, which may be literally defined as ‘infec-
tion due to dark-walled fungi’, i.e., those with the dark
pigment melanin. While rare, C. bantiana (formerly
Cladosporium bantianum, Cladosporium trichoides and
Xylohypha bantiana) is the most common agent of this
disease.
Although infections caused by dematiaceous fungi
are not common, they are being increasingly recog-
nized as being involved in human disease, particularly
in the immunocompromised host [2,3]. They can cause
soft-tissue infection, sinusitis, mycetoma and CNS
abscesses. In particular, C. bantiana has a high
specificity for the CNS as evidenced in a recent
extensive review of 101 cases of cerebral phaeohypho-
mycosis in which 48 cases were associated with C.
bantiana [2]. The infection usually results from hema-
togenous dissemination from a primary site of inva-
sion, commonly the lung. However, the absence of a
primary focus is not unusual.
Brain abscesses caused by C. bantiana have been
reported in both immunocompetent and immunocom-
promised patients, predominantly in transplant recipi-
ents [413]. Immunosuppression due to corticoid
therapy, neutropenia or diabetes mellitus has also
been associated with infections caused by this mold
[14,15]. Direct inoculation, eye trauma and intravenous
drug use are other known risk factors. Given the
increasing use of immunosuppressive therapies and
organ transplantation, the incidence of rare fungal
diseases, including cerebral mold infections, will cer-
tainly be observed more frequently.
Clinically, patients may present with insidious head-
aches and slow evolving neurological signs. It is
important to stress that fever is not always present
and infection parameters can be normal on admission
of the patient. The abscess can be single or multiple and
is usually easy to identify through CT or MRI studies
[16]. Radiologically, fungal abscesses caused by rare
fungi such as C. bantiana cannot be differentiated with
certitude from bacterial abscesses, primary CNS neo-
plasia or cerebral metastasis. In particular, differentiat-
ing between brain abscesses and cystic brain tumors
such as high-grade gliomas and metastasis is often
difficult, if not impossible [17]. In the immunocompro-
mised host, the differential diagnosis is broader and
opportunistic infections (toxoplasmosis, nocardiosis,
and listeriosis among others) and specific malignancy
like lymphoma should also be considered. Cerebral
biopsy with histological studies and exhaustive micro-
biological cultures for bacteria, mycobacteria and fungi
are considered the gold diagnostic standard and should
always be performed.
The mortality rate of cerebral C. bantiana infection is
high. A recent series confirmed a death rate of 70%
despite surgical resection and systemic antifungal
therapy [1]. Several studies have shown that radical
surgical resection followed by targeted pharmacological
treatment enabled good recovery in some cases [18].
One study of 26 cases of cerebral C. bantiana infections
concluded that radical surgical resection of the CNS
lesions was the best outcome predictor [16]. However,
given that CNS disease by C. bantiana is a rare, life-
threatening condition, recommendations for systemic
antifungal therapy can only be based upon the
experience of isolated cases. Based on a large case
series [16], systemic antifungal treatment does, however,
Fig. 3 MRI coronal reconstruction of T1-weighted contrast-enhanced images at similar rostro-caudal levels. (A) Two days before posoconazole
treatment initiation. Note seeding along biopsy tract. (B) Eleven days after posoconazole treatment the enhancement of the lesions were reduced.
2008 ISHAM,
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appear to affect outcomes. Antifungal therapy is
evolving rapidly and more efficient and better tolerated
new drugs are now available.
Fluconazole is not active against C. bantiana and the
classical medical treatment is amphotericin B i.v. alone
or associated with flucytosine and itraconazole. In the
largest published review of 48 cases, mortality was
as high as 70% despite the use of these antifungal
agents [2]. The major factor causing such high mortal-
ity rates is the poor penetration of amphotericin B
(either as deoxycholate or liposomal form) and itraco-
nazole across the blood-brain barrier [19,20]. Further-
more, major adverse effects associated with the use of
these drugs often limit and force an interruption of
treatment. Amphotericin B is known for its renal
toxicity and electrolyte disturbances. Flucytosine use
is limited by its high bone marrow toxicity. Itracona-
zole is an azole used as standard treatment but its oral
formulation presents large inter-individual differences
in gastrointestinal absorption which is a major limita-
tion and necessitates monitoring of drug levels.
Voriconazole or posaconazole are new second-gen-
eration triazole compounds and represent very attrac-
tive options to replace itraconazole in C. bantiana
cerebral infections. Both show broad antifungal spec-
trum in vitro, including C. bantiana, with a very good
oral bioavailability, high volume distribution and high
tissue concentration including the CNS [21]. Successful
treatment of C. bantiana cerebral infections with both
compounds has been reported recently [22,23]. The
most common side effects reported with voriconazole
are transient visual disturbances and liver toxicity [24].
Posaconazole is also very active, both in vitro and in
vivo, in other human fungal infections such as asper-
gillosis or zygomycosis [15,21,25]. Efficacy of posaco-
nazole was shown to be superior to itraconazole or
amphotericin B in a recent mouse model of C. bantiana
infection [26]. Posaconazole could be considered as an
alternative to voriconazole in cases of pre-existing liver
disease or side effects during treatment as occurred in
our patient. The case reported herein showed a rapid
reduction in liver enzymes after a switch from vorico-
nazole to posaconazole treatment and signs of radi-
ological improvement following posaconazole
introduction that were not observed during voricona-
zole treatment. Other new antifungals are the echino-
candins, of which three are currently available, i.e.,
caspofungin, micafungin, and anidulafungin. They
have limited toxicity profiles and minimal drugdrug
interactions. Unfortunately, black molds are less sus-
ceptible to them.
New antifungal drugs such as voriconazole or
posaconazole will probably lead to an improvement
of the prognosis of cerebral fungal abscesses but it
should be kept in mind that, whenever possible,
neurosurgical radical removal of the abscess is currently
the treatment of choice and its role will probably not
change despite new compounds.
Conclusions
Although rare, C. bantiana is frequently associated with
CNS abscesses. However, other rare fungal etiologic
agents should not be excluded from the diagnosis even
in the immunocompetent host. Biopsy and microscopic
observations, along with microbiological studies for
bacteria, mycobacteria and fungi should always be
performed to confirm the diagnosis in cases of evolving
intracerebral mass lesions. A multidisciplinary ap-
proach among neurosurgeons, infectious disease spe-
cialists and microbiologists is mandatory in all cases of
rare cerebral fungal disease in order to correctly
interpret test results and optimize antifungal therapy.
The latter is rendered difficult because of the rarity of
such diseases, difficulties in extrapolating drug efficacy
from in vitro susceptibility testing, availability of several
new potent drugs, experience in adverse events and
drug-drug interactions. Promising new therapies are
currently available and additional studies will confirm
soon if their introduction into clinical practice will
really translate into improved survival. Despite the
often fatal outcome, we encourage clinicians to con-
sider newer therapeutic approaches for these life-
threatening infections when resection is not possible.
Acknowledgements
We are grateful to Kalthum Bouchuigui-Waf for her
microbiological support.
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... Finally, to identify species of fungal origin, additional sequencing methods need to be used like 29S rRNA sequencing or internal transcribed sequencing (ITS). [10][11][12] Similar to standard culture methods, use of sequencing for detection of causal microbes requires clinical correlation. ...
... At his 2-month follow-up, infectious disease discontinued the IV antibiotics, but recommended continuing with oral voriconazole for 1-2 additional years given the severe morbidity and mortality associated with an unlikely Cladosporium infection. 11,20 Imaging at 2 months postdischarge showed both resolution of enhancement and DWI restriction, no hydrocephalus suggestive of resolution of the abscess (Figure 2). To date, the patient is recovering well with no seizures or focal deficits. ...
... The discrepancy in sequencing results presented a significant conundrum. The significant morbidity and mortality (reaching 70% 11,20 ) associated with cerebral infection of Cladosporium prompted treatment of systemic antifungals (i.e., amphotericin B, voriconazole). However, it is important to note that this intervention is not benign. ...
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Fonsecaea monophora is a species of Fonsecaea that belongs to Chaetothyriales. It is usually isolated from tropical and subtropical regions, causing reactive inflammation, skin abscesses, and pain. Cerebral infection caused by F. monophora is rare but often fatal. Diagnosing this disease at an early stage is difficult, and appropriate antifungal therapy is often delayed as a result. We report the case of a 53-year-old woman with type 2 diabetes who presented with a headache 2 months ago and progressive right-sided weakness of 1 month’s duration. Magnetic resonance imaging revealed a space-occupying lesion in the left frontal lobe and corpus callosum. The cystic mass was removed by surgical intervention, and the identification of the sample based on sequencing of the internal transcribed spaced region in BLAST-N search showed that the sequences producing most significant alignments were F. monophora or similar (query cover 99%, E value 0.0, per ident 99.84). The patient was treated with a 3-month course of twice daily voriconazole, leading to complete recovery.
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Background: Amongst the infections in kidney transplant recipients, brain abscess represents an uncommon life-threatening complication. Mortality continues to be high despite improvements in diagnostics and therapeutics. Method: We conducted an observational study, describing the incidence, presentation, implicating pathogen, management and outcome of brain abscess following kidney transplantation at our centre. Result: Amongst the 1492 patients who underwent kidney transplantation at our centre between June 1991 and January 2023 (cumulative follow-up: 4936 patient-years), five fe- males and four males, developed brain abscesses. The incidence proportion (risk) is 0.6% with an incidence rate of 6.03 cases per 1000 patient years. The median duration from transplant to development of brain abscess was 5 weeks (range: 4 weeks to 9 years). The commonest presentation was a headache. A definitive microbiological diagnosis was established in eight out of nine patients. The commonest implicated organism was a dematiaceous fungus, Cladophialophora bantiana (3 patients, 33.3%). Despite the reduction in immunosuppression, surgical evacuation and optimal medical therapy, five (55.55%) patients succumbed to their illness. Conclusions: Brain abscesses following kidney transplantation is an uncommon, life-threatening condition. It usually occurs in the early post-transplant period and the presentation is often subtle. Unlike immunocompetent individuals, a fungus is the most common causative organism in those with solid organ transplants. The management in- includes a reduction in immunosuppression, early antimicrobial therapy, and surgical decompression.
Article
Background and Aims While automation has the advantage of objectivity, ease of use, and reproducibility with well-defined end points of agglutination reaction, standardization of these methods has still not been possible. The aim of the present study was to compare results obtained by manual conventional test tube technique (CTT) with semi-automated, column agglutination technique (CAT), and fully automated hemagglutination/solid-phase red cell adherence (HA/SPRCA) by calculating and comparing correlation and median immunoglobulin M (IgM) and immunoglobulin G (IgG) titer. Materials and Methods This was a prospective, observational study conducted from October 2019 to March 2020. All consecutive A, B, and O group donors who consented to participate were included in the study. All samples were consecutively tested by CTT, CAT, and HA/SPRCA. Results A total of 300 (100 each from A, B, and O blood groups) donors were included. IgG titers were higher than IgM titers in most group O individuals. This difference was more evident with the use of CAT. The correlation between CTT and CAT was found to be strong, whereas the correlation between CTT and HA/SPRCA was found to be variable for anti-A and anti-B IgG and IgM titers. When measured by CTT and CAT, median anti-A and anti-B titer results for group O individuals were similar. Anti-A and anti-B median titer results obtained by CTT and CAT for group A and B individuals were also similar. Conclusion Semi-automated method (CAT) shows higher ability in detecting ABO isoagglutinins than the manual method (CTT) and automated method (HA/SPRCA). These methods cannot be used interchangeably.
Article
Background and Aims Titration is a time-consuming procedure even when automated. The aim of the present study was to identify the variation in ABO titers with donor characteristics in Group O individuals. Materials and Methods This was a prospective, observational study conducted from January 2019 to March 2020. All consecutive O group donors were included. All samples were tested by conventional tube technique (CTT). Demographic and anthropometric details of the donors such as gender, age, religion, height, weight, first-time/repeat donor, and state of residence were recorded. The high-titer group included individuals with anti-A and anti-B ≥128, and the low-titer group included individuals with anti-A and anti-B <128. Results A total of 2000 Group O whole blood donors were included. A higher percentage of donors were older than 30 years of age (55.3%), males (90.7%), Hindu (87.15%), belonging to Uttar Pradesh (70.85%), height more than 160 cm (88.85%), weight more than 65 kg (82.2%), body mass index (BMI) more than 23 (86.15%), body surface area more than 1.7 m ² (89.95%), and first-time donors (68.4%). The donor age, height, weight, BMI, and body surface area were found to have a weak correlation with anti-A and anti-B titers performed by CTT. The correlation between female and male gender was poor in high- as well as low-titer category. Conclusion A definite variation in antibody titers is seen with a change in donor demographics and anthropometrics. However, none of the variables helps as a screening tool for identifying the North Indian healthy donors who possess a high or low titer.
Article
We report long-term survival in a child who developed Cladophialophora bantiana brain abscess after liver transplantation with prolonged antifungal medications. A 6-year-old boy developed a left frontal abscess 1 month after orthotopic liver transplantation. Computed tomography-guided stereotactic aspiration was done which grew C. bantiana . The child was started on voriconazole and amphotericin B. Two months later, he underwent left frontal craniotomy with debridement for increase in intracranial lesions. Amphotericin B was administered for 3 weeks. He was discharged on oral posaconazole. On stopping posaconazole after 6 months, the child developed convulsions. Hence, it was restarted. Posaconazole was continued for 6 years and stopped. He is 11 years post liver transplant doing well. C. bantiana brain abscess in a child after liver transplant is very rare and is associated with high mortality. Improved survival mandates surgical evacuation of abscess and prolonged antifungal therapy.
Article
Background and Aims When determining ABO antibody titers, IgG antibodies can be masked by immunoglobulin M (IgM) antibodies. Hence, the measurement of actual concentration of IgG requires methods such as heat inactivation (HI) of plasma. This study was aimed at determining the effects of HI on IgM and IgG titers performed by conventional test tube (CTT) technique and column agglutination technique (CAT). Materials and Methods This was a prospective, observational study conducted from October 2018 to March 2020. All consecutive O group donors who gave consent for participation were included in the study. All samples were consecutively tested by CTT and CAT, before and after HI (pCTT and pCAT). Results A total of 2005 donors were included. IgG titers were found to be more than IgM titers. pCTT IgG results are similar or lower when compared to results obtained by solid-phase red cell adherence (SPRCA), whereas pCAT IgG titers were higher with pCAT when compared to hemagglutination (HA)/SPRCA. The results of titers obtained by pCTT were lower as compared to pCAT and HA/SPRCA, with majority giving results <64. The median IgG and IgM titers for both anti-A and anti-B were highest in pCAT, whereas the median IgG and IgM anti-A and anti-B titers were similar to HA and pCTT. Conclusion Results obtained by HA/SPRCA were closer to results obtained by pCTT, with the advantage of less time consumption, automation requiring less expertise, and no interobserver variation. Titers obtained by pCAT were higher in comparison to HA/SPRCA and pCTT results, due to high sensitivity.
Article
A 75-year-old immunocompetent male presented with a right orbital cellulitis after a foreign body penetrating injury. He was taken for orbitotomy with foreign body removal and started on broad-spectrum antibiotics. Intra-operative cultures were positive for Cladophialophora bantiana, a mold known for causing brain abscesses with no prior reports of orbital invasion in the literature. Following culture results, the patient was managed with voriconazole and required multiple orbitotomies and washouts for infection control.
Article
Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58–81% of concentrations measured by HPLC, whereas only 15–41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.
Article
Bacterial brain abscesses occur in approximately 1500 to 2500 patients each year in the United States. Multiple abscesses have been noted in 10 to 50% of these patients. The goal of this study was to better define the roles of surgery and medical management in patients harboring multiple brain abscesses and to develop an algorithmic approach to the treatment of these complex patients. Between 1976 and 1992, 16 patients with multiple brain abscesses were treated by a single physician (M.L.R.). The ages of the patients ranged from 1.5 to 73 years (median, 47 yr). In all patients, a diagnosis of multiple abscesses was made by computed tomography (15 patients) or magnetic resonance imaging (1 patient) brain scans. The number of abscesses per patient ranged from 2 to 30, and the abscesses were located in all regions of the brain. Thirteen received a combination of antibiotics and surgical drainage, and three received antibiotics only. Surgery was performed on abscesses larger than 2.5 cm or on those situated in critical areas of the brain or causing significant mass effect. Excision and open aspiration via craniotomy and stereotactic aspiration were analyzed on the basis of the location of the lesion and infecting organism. Any abscess that enlarged after 2 weeks of antibiotics or that failed to shrink after 3 to 4 weeks of antibiotics was again aspirated or excised. Forty-three surgical procedures were performed in 13 patients, and 8 (62%) of the patients operated on required more than one surgical procedure. No significant morbidity was observed in any of the surgical procedures. Antibiotics were administered intravenously for an average of 6 to 8 weeks and were adjusted according to organism type and sensitivity to antibiotics. One patient (6%) died, and the remaining 15 patients had resolution of all abscesses and good neurological recovery within 6 months. On the basis of these results, we propose a combined surgical and medical approach to the treatment of patients with multiple brain abscesses. We recommend the aggressive surgical drainage of all abscesses larger than 2.5 cm in diameter, combined with 6 to 8 weeks of intravenous antibiotics. Biweekly computed tomography or magnetic resonance imaging is necessary to closely monitor patients for evidence of abscess growth or failure to resolve despite antibiotics, prompting another operation. The application of this combined approach should yield cure rates of more than 90% in patients with multiple brain abscesses, a result similar to that expected when treating patients with solitary lesions.
Article
The oral azole drugs--ketoconazole, fluconazole, and itraconazole--represent a major advance in systemic antifungal therapy. Among the three, fluconazole has the most attractive pharmacologic profile, including the capacity to produce high concentrations of active drug in cerebrospinal fluid and urine. Ketoconazole, the first oral azole to be introduced, is less well tolerated than either fluconazole or itraconazole and is associated with more clinically important toxic effects, including hepatitis and inhibition of steroid hormone synthesis. However, ketoconazole is less expensive than fluconazole and itraconazole--an especially important consideration for patients receiving long-term therapy. All three drugs are effective alternatives to amphotericin B and flucytosine as therapy for selected systemic mycoses. Ketoconazole and itraconazole are effective in patients with the chronic, indolent forms of the endemic mycoses, including blastomycosis, coccidioidomycosis, and histoplasmosis; itraconazole is also effective in patients with sporotrichosis. Fluconazole is useful in the common forms of fungal meningitis--namely, coccidioidal and cryptococcal meningitis. In addition, fluconazole is effective for selected patients with serious candida syndromes such as candidemia, and itraconazole is the most effective of the azoles for the treatment of aspergillosis.
Article
The dematiaceous fungi appear to be an increasing cause of human disease. At The Methodist Hospital, in Houston, Texas, five cases of serious disease caused by these fungi occurred between 1987 and 1992. Cerebral abscesses with Xylohypha bantiana followed treatment for lymphoma. An infection of the lower extremity with Exophiala jeanselmei var. castellanii followed cardiac surgery. Peritoneal growth of Alternaria tenuissima was a complication of peritoneal dialysis. Cerebral abscesses with Dactylaria gallopava occurred in a liver transplantation patient. A traumatic ankle wound contaminated with dirt led to an infection with Phialophora repens. All patients except the last were immunocompromised at the time of the infection; diabetics and patients on steroids may be at particular risk.
Article
Neurologic complications occur in about 30% of renal transplant patients, infections being the most common. We encountered three such patients and present our experience in the management of such cases. Three cases of brain abscess in renal transplant recipients are reported. These patients presented from 9-60 months after the transplant. One patient had a pyogenic abscess; in the second the organism identified was Nocardia asteroides; in the third, a fungal infection was responsible. In two patients excision of the abscess was done, while in one repeated aspirations with intracavitary antibiotics were used. All received systemic antimicrobial therapy. Central nervous system (CNS) complications, specifically infections, are quite common in renal transplant recipients, but reports of brain abscesses in these patients are very rare. The treatment options for such patients are discussed.
Article
Cladophialophora bantiana (Cladosporium trichoides) is a black fungus recorded rarely as a cause of brain abscess. Only 21 cases have been reported in the literature world-wide. We describe the first case seen in Brazil. A 30 year old, previously healthy female, HIV negative, came to the hospital with a clinical diagnosis of brain tumor. After biopsy and culture of the lesion, it was found that she had an abscess due to Cladosporium trichoides. During the following five months, the patient underwent three more surgical brain interventions to totally remove the area of compromised tissue. In addition to surgery, amphotericin B, both intravenously and intrathecally, was used followed by itraconazole orally, without success. Six months after the first surgical intervention, the patient died. The worldwide experience with diagnosis and treatment of patients with this diseases is reviewed.
Article
Cerebral phaeohyphomycosis caused by Cladophialophora bantiana, a dematiaceous fungus, is a rare disease. The majority of cases have been reported among immunocompetent patients; only 4 cases have been published that describe transplantation patients. The overall prognosis is poor. Surgical therapy in combination with chemotherapy with itraconazole is recommended. We report the case of a heart transplant recipient with cutaneous, cerebral, and lung manifestation of Cladophialophora bantiana who died despite surgical and systemic, high-dosage itraconazole treatment.