amphotericin-b and Central-Nervous-System-Fungal-Infections

Topics: Adolescent; Adult; Allografts; Amphotericin B; Central Nervous System Fungal Infections; Child; Disease-Free Survival; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Survival Rate; Voriconazole

Cryptococcosis caused by Cryptococcus gattii, is a life threatening fungal infection with recently increasing prevalence. C. gattii is a species complex comprising multiple independent species. However, many biological characteristics and clinical features of cryptococcosis due to C. gattii are relatively less well defined. In this paper, we identify two cases of C. gattii infection, and laboratory findings of genotype VGI and VGII in two groups of apparently immunocompetent Chinese individuals respectively. Upon detailed review of all 35 cases of C. gattii infections, it was observed that C. gattii can cause debilitating illness in both immunocompetent and immunocompromised individuals. Cryptococcosis due to C. gattii is a serious systemic fungal infection, with pulmonary central nervous system tropism. Epidemiologically, C. gattii infection is not only restricted in tropical and subtropical regions, but also in other geographical settings.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Asian People; Central Nervous System Fungal Infections; Cryptococcosis; Cryptococcus gattii; Drug Therapy, Combination; Female; Flucytosine; Genotype; Geography; Humans; Immunocompromised Host; Male; Middle Aged; Prevalence; Recurrence; Spinal Puncture; Treatment Outcome; Treatment Refusal; Young Adult

Severely immunocompromised patients such as those with haematological malignancies and haematopoietic stem cell transplant recipients are at an increased risk of acquiring invasive mould infections. Fusarium, a ubiquitous fungus, can cause potentially fatal infections in such hosts. It usually manifests as skin lesions, fevers and sino-pulmonary infections. Brain abscesses have been reported, but are relatively uncommon. We report a case of a 50-year-old patient with acute lymphocytic leukaemia and failed autologous peripheral stem cell transplant that presented with new onset seizures and was found to have Fusarium solani brain abscess. Nasal route was the presumed mode of entry of the fungus into the cerebrum. Treatment comprised surgical excision of the lesion, and antimycotic therapy with liposomal amphotericin B and voriconazole. Despite aggressive therapy, patient succumbed to the disease. We have provided an overview of infections secondary to Fusarium, along with a review of the central nervous system involvement by this pathogenic mould.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System Fungal Infections; Fatal Outcome; Female; Fusariosis; Fusarium; Humans; Immunocompromised Host; Middle Aged; Peripheral Blood Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography; Seizures; Voriconazole

Fungal granulomas of the central nervous system are rare and have a high rate of mortality and morbidity, irrespective of treatment. The authors report their experience of managing 66 patients during 15 years and discuss the clinical, radiological, surgical, and pathologic findings. This series is among the largest reported.. A retrospective analysis was performed on patients with intracranial fungal granulomas (ICFGs), treated in the authors' institution, between January 1997 and May 2011. Only mass-forming histopathologically proven ICFGs were included in this study.. The age of the patients ranged from 7 years to 67 years (mean = 32.3 years), and most patients were in the third and fourth decades of life. The study population comprised 47 male and 19 female patients. The most common symptom was headache (41 patients), followed by vomiting (16 patients) and blurring of vision (16 patients). Only 3 patients presented with fever. The duration of symptoms was less than 6 months in all cases and less than 3 months in 39 cases. Anterior cranial fossa and frontal lobe was involved in 35 cases (54.5%), followed by middle cranial fossa in 20 cases (30.3%). Three cases had granulomas in the cerebellopontine angle. Three cases had multicompartmental involvement, and 4 had multilobar involvement. Nine patients had predisposing factors for fungal infection Based on clinical and imaging data, preoperative diagnosis of a possible fungal lesion was made in 44 (some had only computed tomography imaging) patients. All the patients were treated surgically, followed by antifungal treatment with amphotericin-B and/fluconazole/itraconazole for a period of 6 weeks. Eight patients had symptomatic recurrence of lesions 3-12 weeks after treatment and underwent reoperation. Six patients were lost to follow-up. Nine patients died in the postoperative period (within 30 days postoperatively). Fifteen patients died during follow-up because of recurrent lesions, repeat surgery, renal failure, and unrelated causes. Overall mortality was 24 (36.3%). Poor neurologic status before surgery, emergency craniotomy, severe brain edema with mass effect, and opening of ventricles during surgery were associated with poor outcome. Aspergillus species were the causative organism in an overwhelming majority of patients (n = 52) followed by Mucor in 7 cases, Cladosporium in 3 cases, eumycetoma in 2 cases, and maduramycosis and blastomycosis in 1 case each.. ICFGs have high rates of morbidity and mortality. Early diagnosis, radical surgery, and antifungal treatment for 6 weeks may improve outcome. Poor neurologic status of patients at the time of presentation, immunocompromised state, contamination of ventricular cerebrospinal during surgery, and renal failure (attributable to amphotericin-B) are associated with poor outcome.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Child; Craniotomy; Drug Therapy, Combination; Emergency Treatment; Female; Fluconazole; Granuloma; Humans; Immunocompromised Host; Itraconazole; Male; Middle Aged; Neuroimaging; Recurrence; Renal Insufficiency; Reoperation; Retrospective Studies; Risk Factors; Survival Rate

Considered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

Topics: Amphotericin B; Antifungal Agents; Azoles; Central Nervous System Fungal Infections; Drug Resistance; Humans; Naphthalenes; Paracoccidioidomycosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfonamides; Terbinafine

Rhino-orbito-cerebral mucormycosis is an acute onset and often fatal disease. Risk factors include uncontrolled diabetes mellitus, hematological malignancies, and long-term corticosteroid use. Early diagnosis and treatment are important. The underlying causes should be treated, surgical debridement should be performed and appropriate antifungal drugs should be given. In this article, we report two diabetic ketoacidosis patients who developed rhino-orbito-cerebral mucormycosis and were treated with surgical debridement and amphotericin B therapy.

Topics: Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Debridement; Diabetic Ketoacidosis; Humans; Male; Middle Aged; Mucormycosis; Nose Diseases; Orbital Diseases; Risk Factors

Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patient's head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug-resistant infection following a tsunami disaster.

Topics: Aged; Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System Fungal Infections; Delayed Diagnosis; Female; Humans; Japan; Lung Diseases, Fungal; Magnetic Resonance Imaging; Near Drowning; Pyrimidines; Scedosporium; Survivors; Tomography, X-Ray Computed; Triazoles; Tsunamis; Voriconazole

Mucormycosis is a rare fungal infection that affects immunocompromised patients, and the rhinoorbitocerebral presentation is the most common clinical form of the disease, often associated with diabetes mellitusThe treatment is complex and involves amphotericin B and surgery. Studies show increasing success without or with minimal surgeries. The authors present the case of a diabetic woman with a 1-month history of intranasal and right periorbital pain associated with progressive deficit of various cranial nerves, sudden amaurosis and homolateral ptosis. Rhizopus oryzae species was identified in pus in the nasal mucosa. She was treated with antifungal therapy and minimal surgical debridement with success. The authors decided on publication because of the rarity of this entity, alerting for the need of a high suspicion index for the diagnosis, which should be made as early as possible due to the high mortality rate, as well as presenting data about the increasing discussion of therapeutic strategies, with some new approaches that prioritise minimal surgeries.

Topics: Amphotericin B; Central Nervous System Fungal Infections; Debridement; Diabetes Mellitus, Type 2; Female; Humans; Immunocompromised Host; Middle Aged; Mucormycosis; Nose Diseases; Orbital Diseases; Rhizopus; Treatment Outcome; Turbinates

Cryptococcal infection in CNS is frequently seen in HIV patients and those with other immunosuppressed conditions. However, cryptococcal granuloma in CNS in immunocompetent patient is rare. We present one new case of cryptococcoma and review literature to illustrate diagnosis and treatment of these lesions.. We conducted literature search in Pubmed search engine of the National Center for Biotechnology Information.. Seventeen cases of CNS cryptoccoma in immunocompetent patients, including ours, have been reported to date. Of them, two patients had lesions inside spinal cord, and C. neoformans var. gattii was identified in three cases. All patients were symptomatic with normal immunocompetency although two patients had type 2 diabetes mellitus and one had torsades de pointes. Eight patients received surgical treatment and all were given antifungal agents except one suspected of teniasis.. With literature reports and our experiences, we suggest that ring shaped enhancement of mass lesion with or without cystic changes in MR scan may indicate cryptococcoma, but definitive diagnosis relies on pathology study of lesion specimen. Open surgery and anti-fungal therapy should be scheduled, and outcome of cryptococcoma is largely determined by its locations.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Child; Cryptococcosis; Female; Granuloma; Humans; Immunocompetence; Injections, Intravenous; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Tomography, X-Ray Computed; Young Adult

Blastomycosis is an endemic mycosis caused by the dimorphic fungus Blastomyces dermatitidis. Although this disease primarily involves the lungs, the clinical spectrum of blastomycosis can range from subclinical infection to extrapulmonary dissemination. The central nervous system (CNS) form of blastomycosis is primarily treated with an amphotericin B formulation, but associated toxicities of this agent preclude its use in some patients. Voriconazole is a broad-spectrum triazole antifungal that has emerged as a potential treatment option for CNS blastomycosis because of its excellent penetration into the cerebrospinal fluid and brain tissue.. To evaluate evidence for the use of voriconazole in the treatment of CNS blastomycosis.. A literature search was performed using MEDLINE, EMBASE, Cochrane Database, and PubMed (all up to April 2009). Search terms included voriconazole, blastomyces, blastomycosis, CNS, cerebral, and central nervous system.. English-language clinical trials, case reports, treatment guidelines, and background material were searched for voriconazole safety and efficacy data. References of reviewed articles were examined and used to identify additional sources.. A search of the literature yielded 2 published case reports and 2 case series documenting a total of 7 cases of CNS blastomycosis. In all cases, CNS blastomycosis was successfully treated sequentially with amphotericin B followed by voriconazole. To date, no clinical trials have evaluated the use of voriconazole in treating CNS blastomycosis. Ages of the patients with documented cases of CNS blastomycosis ranged from 14 months to 63 years. In at least 5 cases, CNS blastomycosis presented as lesions in the brain detected by magnetic resonance imaging. One case presented as focal splenic lesions. The remaining 2 were diagnosed based on neuroimaging studies or positive spinal fluid serology. Prior to receiving voriconazole, patients were treated with an amphotericin B formulation combined in some situations with either fluconazole or itraconazole. Subjects underwent treatment with voriconazole for an average of 11 months, with disease remission or stabilization detected in all cases.. Further studies are needed to fully elucidate the role of voriconazole in the treatment of CNS blastomycosis. It nonetheless may be considered as an azole option for either follow-up therapy after liposomal amphotericin B therapy or as salvage therapy in patients intolerant of amphotericin B or other azoles.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Blastomyces; Blastomycosis; Central Nervous System Fungal Infections; Child; Child, Preschool; Humans; Infant; Magnetic Resonance Imaging; Middle Aged; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole; Young Adult

Zygomycosis of the central nervous system (CNS) can manifest in three distinct clinical forms, as rhinocerebral zygomycosis, as disseminated zygomycosis with CNS involvement, and as isolated cerebral zygomycosis. We present a case of a 2-year-old boy with leukaemia and disseminated zygomycosis, caused by Absidia corymbifera, involving the brain, spinal cord, lung and liver. The child received treatment with liposomal amphotericin B and posaconazole for 6 months. Although the lesions of the lungs and liver resolved, those of the CNS persisted and the child is in a vegetative state. A review of the literature after 2004 identified ten additional cases of disseminated zygomycosis with cerebral involvement, all but one of which had concurrent lung infection. The most common underlying disease in these cases was haematological malignancy and the mortality rate was 70%. Disseminated zygomycosis with cerebral involvement is a fatal disease. Early recognition and prompt intervention with combined medical and surgical treatment may improve the outcome.

Topics: Absidia; Amphotericin B; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Child, Preschool; Humans; Liver; Lung; Male; Mucormycosis; Spinal Cord; Triazoles

Zygomycosis is an invasive fungal infection with extremely high mortality caused by filamentous fungi which belong to Class Zygomycetes (Rhizopus spp., Mucor spp., Cunninghamella spp., etc). Despite of the similarities of the ecological characteristics and of the patients' backgrounds, zygomycosis is much rarer than invasive aspergillosis. In addition to well known immunosuppressive risk factors (hematological malignancy, hematopoietic stem cell or solid organ transplant, prolonged neutropenia, corticosteroid, etc), diabetic ketoacidosis, iron overload, and administration of deferoxamine are specific factors predisposing zygomycosis. Rhinocerebral, pulmonary and disseminated disease is characteristic forms. The mainstay of the treatment is surgical resection, reversal of immunosuppressive factors, and administration of high-dose amphotericin B or its liposomal formulation. Because of the difficulty of culture detection and the absence of reliable serological diagnostic methods, premortem diagnosis and no delaying of effective treatment remain a challenge to physicians.

Topics: Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Diabetes Complications; Drug Delivery Systems; Humans; Immunocompromised Host; Iron Overload; Liposomes; Lung Diseases, Fungal; Neutropenia; Prognosis; Risk Factors; Surgical Procedures, Operative; Zygomycosis

A systemic and endemic emerging mycosis in Latin America, paracoccidioidomycosis, is characterised by its chronicity and by the severity of the disseminated form in healthy individuals, as well as in immunocompromised individuals co-infected with HIV, resulting, in the latter, in a mortality rate in the range of 30 - 45%. The long (several years) duration of treatment results from the immunosuppression induced by the disease or from the survival capacity of the fungus in tissue. A few controlled studies and case reports have shown that fast-acting azolic and sulfa derivatives are useful treatment alternatives for patients presenting milder forms of the disease. However, when using such drugs, treatment regimens of longer duration are required for the maintenance of patients with more severe forms. The search for new alternatives for treating the most severe forms is an ongoing challenge. Novel treatments may be found among new classes of drugs, drug combinations, or agents capable of modulating the immune response, such as a peptide derived from the 43-kDa Paracoccidioides brasiliensis glycoprotein.

Topics: Amphotericin B; Central Nervous System Fungal Infections; Drug Resistance; Fluconazole; Follow-Up Studies; Humans; Immunocompromised Host; Itraconazole; Ketoconazole; Paracoccidioidomycosis; Pyrimidines; Sulfonamides; Triazoles; Voriconazole

Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Itraconazole; Male; Middle Aged; Mycoses; Risk Factors; Treatment Outcome

Invasive aspergillosis is an increasing cause of morbidity and mortality in immunocompromised patients. Extension of invasive aspergillosis to the central nervous system (CNS) is associated with an exceeding high mortality which approaches 100%. One major factor contributing to this devastating outcome is a poor penetration into the CNS of frequently used antifungal drugs, such as amphotericin B or itraconazole. Voriconazole, a new triazole with broad activity against various fungi, including Aspergillus species, shows superior activity in invasive aspergillosis compared to treatment with conventional amphotericin B. Voriconazole readily penetrates the blood-brain barrier yielding fungicidal drug concentrations within the CNS. A growing number of patients with CNS aspergillosis has been successfully treated with voriconazole in recent years. The pharmacological properties, the broad antifungal activity and the promising clinical data suggest that the use of voriconazole in CNS aspergillosis might improve the outcome in this otherwise devastating clinical condition. However, additional clinical data are needed to determine more precisely the role of voriconazole in CNS aspergillosis. In this review, we have compiled the available pharmacological and clinical data on CNS aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blood-Brain Barrier; Caspofungin; Central Nervous System Fungal Infections; Echinocandins; Female; Flucytosine; Humans; Immunocompromised Host; Itraconazole; Lipopeptides; Male; Peptides; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Case-Control Studies; Central Nervous System Fungal Infections; Child; Child, Preschool; Clinical Trials as Topic; Cohort Studies; Drug Combinations; Female; Humans; Male; MEDLINE; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Prognosis

Although blastomycosis of the central nervous system (CNS) occurs in approximately 4% of patients with blastomycosis, recurrent CNS blastomycosis is very rare. We review the clinical features, treatment, and outcome of 4 previously reported cases. We also report a case of recurrent CNS blastomycosis successfully treated with surgery and liposomal amphotericin B after an inadequate response to amphotericin B therapy. This treatment may be an alternate approach for management of similar cases.

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Brain; Central Nervous System Fungal Infections; Humans; Liposomes; Magnetic Resonance Imaging; Male; Middle Aged; Radiography; Recurrence; Treatment Outcome

Recently, improved response and survival rates in patients treated with voriconazole and neurosurgery for central nervous system (CNS) aspergillosis have been reported. We assessed retrospectively the outcome in 17 patients with definite or probable CNS aspergillosis treated with amphotericin B alone (n = 15) or in combination with 5-fluorocytosine (n = 3) or itraconazole (n = 2). Four patients underwent neurosurgery. The mortality rate was 100% with a median survival of only 10 days (range: 3-60) after onset of first symptoms or first radiological evidence of CNS aspergillosis. In conclusion, treatment with amphotericin B and itraconazole has negligible efficacy in CNS aspergillosis.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Central Nervous System Fungal Infections; Child; Drug Therapy, Combination; Female; Flucytosine; Humans; Itraconazole; Male; Middle Aged; Neuroaspergillosis; Treatment Outcome

Rhinocladiella mackenziei is a highly neurotropic fungus, mainly reported from the Middle East. However, in recent years, there have been some cases from outside this region. We described an additional fatal case of R. mackenziei cerebral infection for the first time from Turkey and made a literature review of all previously reported cases. During 34 years (1988-2022), there have been 42 R. mackenziei brain abscess cases. Most patients have been reported from Saudi Arabia (n = 14, 33.3%). It is noteworthy that 40.5% of patients, including our case, were immunocompetent at initial diagnosis and mostly presented with a single lesion (n = 10, 23.8%). The most frequent comorbidities were solid organ transplant (n = 9, 21.4%), diabetes mellitus (n = 6, 14.3%), malignancy (n = 6, 14.3%) and prior surgery (n = 3, 7.1%). The most commonly used initial antifungal regimen were amphotericin B together with itraconazole (n = 9, 21.4%), combinations of lipid preparations of amphotericin B, voriconazole and/or posaconazole (n = 9, 21.4%) and amphotericin B alone (n = 8, 19%). Although both surgical procedures and antifungal medication in the majority of patients were performed, mortality rates remained high (90.4%). The area at risk of R. mackenziei cerebral abscess cases extends to other countries. Clinicians should be aware of this emerging disease and take a detailed travel history in patients with atypical and undocumented brain abscesses. Our case confirms the hypothesis that this fungus might spread more widely than previously predicted regions.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System Fungal Infections; Humans; Turkey

Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; beta-Glucans; Biomarkers; Central Nervous System Fungal Infections; Cerebrospinal Fluid; Chronic Disease; Diagnostic Tests, Routine; Female; Healthy Volunteers; Humans; Male; Mannans; Middle Aged; Retrospective Studies; Treatment Outcome; Triazoles

Cerebral abscess due to pigmented molds is a rare but usually fatal infection occasionally seen in transplant recipients. A 67-year-old man of Iraqi origin underwent a deceased donation renal transplant for renal failure and 2 months later was diagnosed with an abscess in the left posterior frontal lobe of his brain. Subsequent biopsy proved this to be due to the mold Rhinocladiella mackenziei. Further interventions included two operations to aspirate the lesion, voriconazole, then liposomal amphotericin B, then a combination of posaconazole and flucytosine which he continued for over 4 years. He also suffered from right ankle pain and was diagnosed with septic arthritis; R mackenziei was isolated from pus aspirated from the ankle joint. He responded well to the treatment and has had little loss of function, and on CT, the cerebral lesion has stabilized. Beta-D-glucan, initially at very high levels proved useful to monitor response over the 5 years and the latest sample was negative (38 pg/mL). This case is notable for the first disseminated case of this infection, its favorable outcome on a novel antifungal combination and a new approach to monitoring the course of disease.

Topics: Aged; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Ascomycota; Brain Abscess; Central Nervous System Fungal Infections; Humans; Immunocompromised Host; Invasive Fungal Infections; Kidney Transplantation; Male; Treatment Outcome; Triazoles

We present an uncommon case of isolated basal ganglia mucormycosis in a patient without any known cause of immunosuppression, but with a history of drug injection. The patient presented a good clinical and radiological response to antifungal treatment without aggressive surgical debridement (liposomal amphotericin B combined with isavuconazole for 4 weeks followed by isavuconazole as maintenance therapy for 10 months).

Topics: Amphotericin B; Central Nervous System Fungal Infections; Cocaine; Cocaine-Related Disorders; Drug Therapy, Combination; Drug Users; Humans; Magnetic Resonance Imaging; Male; Marijuana Abuse; Middle Aged; Mucormycosis; Nitriles; Pyridines; Substance Abuse, Intravenous; Triazoles

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Brain; Central Nervous System Fungal Infections; Female; Histoplasmosis; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Spinal Cord

Cryptococcal infection has become a public health challenge globally. However, information about cryptococcal infection in patients with hematological diseases remains relatively rare.. HIV-uninfected cryptococcosis cases with hematological diseases admitted to Huashan Hospital from January 2001 to December 2014 were reviewed.. In total, 33 cryptococcosis patients were enrolled, including 12 malignant and 21 non-malignant hematological cases. Twenty-six patients had central nervous system (CNS) involvement, which was observed more often in patients with non-malignancies than with malignancies (20/21 vs. 6/12, P = 0.001) Most patients (25/26) with CNS infection were confirmed by cerebrospinal fluid (CSF) culture or smear, and 100% (20/20) of them tested positive for the CSF cryptococcal antigen test. Eighteen out of 26 cryptococcal meningitis patients were treated with amphotericin B (AmB)-based therapy, 16 of them with AmB deoxycholate (d-AmB) and 2 patients with liposomal AmB. The clinical success rate was 55.6%. D-AmB was well-tolerated at 0.35-0.59 mg/kg/d (median 0.43 mg/kg/d) and only 12 patients had mild adverse events.. CNS cryptococcal infection was more frequent in patients with hematological non-malignancies, and cryptococcal antigen test as well as the CSF fungal culture or smear are suggested for early diagnosis. D-AmB could be used as an alternative therapy for CNS-infected patients with hematological diseases.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Female; Hematologic Diseases; Hematologic Neoplasms; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Tertiary Care Centers; Young Adult

Cryptococcus gattii species complex has evolved as a pathogen in the last two decades causing infection among both immunocompetent and immunocompromised hosts. We aimed to analyse the clinical features of CNS infection caused by C. gattii sensu lato, molecular and antifungal susceptibility profile of this pathogen. Cases diagnosed to have CNS cryptococcosis were included in the study. Cryptococcus recovered from patient's specimen was identified by standard protocol. Species confirmation, mating type and molecular type determination were performed by PCR based methods. Antifungal susceptibility was tested in VITEK2C to amphotericin B, 5-flucytosine, fluconazole and voriconazole. Among 199 cases, 20 (10%) were due to C. gattii, comprising of 75% cryptococcal meningitis and 25% cryptococcoma cases. Young adult males were commonly affected. Headache and vomiting were prominent symptoms and 50% were immunocompromised. Among the isolates, 75%, 20% and 5% were C. tetragattii, C. gattii sensu stricto and C. bacillisporus respectively and all had mating type α. Four (20%) isolates of C. tetragattii and the only isolate of C. bacillisporus were resistant to fluconazole. The most common species isolated from south India is C. tetragattii. The study contributes to the epidemiology of C. gattii and reiterates the need for genotyping and antifungal susceptibility testing.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Cryptococcosis; Cryptococcus gattii; Female; Fluconazole; Genes, Mating Type, Fungal; Humans; India; Male; Meningitis, Cryptococcal; Middle Aged; Prospective Studies; Young Adult

Three months after a kidney transplant, a man experienced an internuclear ophthalmoplegia. Magnetic resonance imaging found a punctuate hyperintensity of the brainstem. Afterwards, the patient presented with peripheral facial paralysis. A complete morphologic assessment showed an increase of the brainstem lesion, together with an excavated pulmonary nodule. Combination therapy with high-dose liposomal amphotericin B and voriconazole was begun for the putative aspergillosis. Owing to its atypical clinical presentation and negative detection of Aspergillus galactomannan antigen on sera, a biopsy specimen of the lung lesion was obtained. Histopathological and mycological investigations allowed the diagnosis of mucormycosis owing to Rhizopus microsporus. Accordingly, voriconazole was replaced with posaconazole. After 5 months, regression of the cerebral lesion was noted. Disseminated mucormycosis in solid-organ recipients is uncommon and mycological diagnosis is challenging. Mortality is high and is increased by diagnostic delay. Treating mucormycosis requires surgical debridement and appropriate antifungal therapy (usually intravenous liposomal amphotericin B). This report suggests that a combination of liposomal amphotericin B and posaconazole can be a therapeutic option in patients with a poor prognosis.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Diagnosis, Differential; Drug Therapy, Combination; Fatal Outcome; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Mucormycosis; Predictive Value of Tests; Rhizopus; Tomography, X-Ray Computed; Treatment Outcome; Triazoles

Rhino-orbito-cerebral mucormycosis(ROCM) is an invasive fungal infection that usually occurs in immunocompromised patients and sometimes presents as orbital apex syndrome(OAS) initially. It is rapidly fatal without an early diagnosis and treatment. We report the cases of invasive ROCM presenting with OAS initially in order to raise the attention of clinicians.. We retrospectively investigated eleven cases of invasive ROCM presenting initially with OAS admitted between January 2006 and December 2013. We analyzed clinical features, results of laboratory and radiological examinations, nasal endoscopy, aggressive surgical excision and debridement, and medical management outcomes of each case.. A total of eleven cases of invasive ROCM with OAS as an initial sign were presented. Mucormycosis was accompanied by type II diabetes mellitus in nine cases, renal transplant in one case, and injury caused by traffic accident in one case. Anterior rhinoscopy revealed palatine or nasal necrotic lesions in all patients, and transethmoidal optic nerve decompression was carried out in three patients at the same time. CT scan revealed rhino-orbital-cerebral involvement in every patient. All patients were given intravenous amphotericin B. Nine patients underwent surgical debridement of necrotic tissue. Three patients survived.. ROCM is a severe, emergent and fatal infection requiring multidisciplinary management. It may often present with OAS initially. For ophthalmologist, mucormycosis must be considered in immunocompromised patients presenting with OAS initially, and anterior rhinoscopy is imperative before hormonotherapy, even in the cases absent of ketoacidosis induced by diabetes mellitus.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Debridement; Eye Infections, Fungal; Female; Humans; Itraconazole; Magnetic Resonance Imaging; Male; Middle Aged; Mucormycosis; Orbit; Orbital Diseases; Paranasal Sinus Diseases; Retrospective Studies; Tomography, X-Ray Computed

Topics: Adolescent; Amphotericin B; Antifungal Agents; Ascomycota; Benzenesulfonates; Brain Abscess; Central Nervous System Fungal Infections; Chronic Disease; Coloring Agents; Debridement; Epidural Abscess; Frontal Lobe; Frontal Sinus; Humans; Lactic Acid; Male; Phenols; Pyrimidines; Sinusitis; Treatment Outcome; Triazoles; Voriconazole

Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4(+) T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4(+) T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Brazil; CD4-Positive T-Lymphocytes; Central Nervous System Fungal Infections; Humans; Itraconazole; Lymphocyte Count; Male; Meningoencephalitis; Paracoccidioides; Paracoccidioidomycosis; Tomography, X-Ray Computed; Viral Load

We present a case of cerebral Scedosporium apiospermum infection presenting with intestinal manifestations in a 64-year-old male patient on immunosuppression for orthotopic liver transplantation. At admission, the patient's chief complaint was chronic watery diarrhea and he was found to have colonic ulcers on endoscopy. His hospital course was complicated by a tonic-clonic seizure caused by a left frontal brain abscess, with the causative agent being identified by culture. He was treated with lobectomy, high-dose intravenous voriconazole, and liposomal amphotericin with clinical, endoscopic, and histologic improvement. To our knowledge, S. apiospermum has not been previously described as a cause of colitis. The septate branching appearance of the Scedosporium species is similar to the more common Aspergillus species. This case of gastrointestinal Scedosporium brings into question previously reported cases of isolated gastrointestinal aspergillosis diagnosed by histopathology. Clinical suspicion for S. apiospermum must be maintained in immunosuppressed patients presenting with neurologic and gastrointestinal symptoms.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System Fungal Infections; Colitis, Ulcerative; Histocytochemistry; Humans; Male; Microscopy; Middle Aged; Psychosurgery; Pyrimidines; Scedosporium; Triazoles; Voriconazole

Blastomyces dermatitidis is a dimorphic fungus which is potentially life-threatening if central nervous system (CNS) dissemination occurs. Sixteen patients with proven or probable CNS blastomycosis are presented. Median duration of symptoms was 90 days; headache and focal neurologic deficit were the most common presenting symptoms. Magnetic resonance imaging (MRI) consistently demonstrated an abnormality, compared to 58% of computed tomography scans. Tissue culture yielded the pathogen in 71% of histology-confirmed cases. All patients who completed treatment of an amphotericin B formulation and extended azole-based therapy did not relapse. Initial nonspecific symptoms lead to delayed diagnosis of CNS blastomycosis. A high index of suspicion is necessary if there is history of contact with an area where B. dermatitidis is endemic. Diagnostic tests should include MRI followed by biopsy for tissue culture and pathology. Optimal treatment utilizes a lipid-based amphotericin B preparation with an extended course of voriconazole.

Topics: Amphotericin B; Azoles; Biopsy; Blastomyces; Blastomycosis; Central Nervous System Fungal Infections; Humans; Magnetic Resonance Imaging; Pyrimidines; Tomography, X-Ray Computed; Treatment Outcome; Triazoles; Voriconazole

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Combined Modality Therapy; Debridement; Diabetes Complications; Early Diagnosis; Endoscopy; Fatal Outcome; Female; Humans; Male; Maxillary Sinus; Middle Aged; Mucormycosis; Nose Diseases; Opportunistic Infections; Oroantral Fistula; Paranasal Sinus Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Pregnancy Complications, Infectious; Sinusitis; Zygomycosis

Topics: Adult; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Eye Infections, Fungal; Female; Humans; Hyphae; Immunocompetence; Male; Maxilla; Middle Aged; Mucormycosis; Nose Diseases; Orbit; Paranasal Sinus Diseases; Pyrimidines; Triazoles; Voriconazole

We present the case of an immunocompetent male who presented with symptoms of meningitis. Yeasts were seen in two consecutive cerebrospinal fluid samples, which were identified by PCR as Sporobolomyces roseus. This yeast is rarely encountered in clinical settings, and has only previously been seen to cause infection in immunocompromised patients. This case highlights the challenges presented by the identification of an unusual pathogen in an unexpected clinical setting.

Topics: Adult; Amphotericin B; Antifungal Agents; Basidiomycota; Central Nervous System Fungal Infections; Cerebrospinal Fluid; DNA, Fungal; Humans; Male; Meningitis; Polymerase Chain Reaction

Histoplasmosis of the central nervous system (CNS) is seen in 10% to 20% of patients with disseminated histoplasmosis and/or in association with immunocompromised patients. Meningitis, arachnoiditis, and hydrocephalus are the most common clinical manifestations of CNS histoplasmosis. Patients with CNS histoplasmosis present similarly to other infectious etiologies, and confirmatory diagnosis is important in the management of these patients. However, diagnosis of CNS histoplasmosis can be difficult, and sometimes performing a parenchymal biopsy is necessary to confirm the diagnosis.. We describe the case of a 41-year-old man with HIV/AIDS who presented with the signs, symptoms, and radiologic evidence of basal meningitis and hydrocephalus. Cerebrospinal fluid (CSF) analysis from multiple lumbar punctures was negative. The patient underwent a neuroendoscopic procedure with diagnostic and therapeutic goals. Internal CSF diversion (endoscopic third ventriculostomy) and biopsy of the floor of the third ventricle and subarachnoid space were performed; surgical biopsies identified noncaseating granulomas, and ventricular CSF was positive for Histoplasmosis antibodies. The patient was treated with liposomal amphotericin B and itraconazole. The patient had resolution of his symptoms immediately after surgery, and 1-month follow-up computed tomography of the head demonstrated resolution of the hydrocephalus. At the last follow-up 12 months postoperatively, the patient has not required insertion of a ventriculoperitoneal shunt.. Clinicians should maintain a high index of suspicion for fungal basal meningitis in patients with AIDS and hydrocephalus. With nondiagnostic lumbar CSF sampling, neuroendoscopy can be considered as an alternative for diagnosis and treatment of basal meningitis and hydrocephalus.

Topics: Adult; Amphotericin B; Antibodies, Fungal; Antifungal Agents; Arachnoiditis; Biopsy; Central Nervous System Fungal Infections; Cerebral Ventricles; Histoplasmosis; HIV Infections; Humans; Hydrocephalus; Itraconazole; Male; Neuroendoscopy; Neurologic Examination; Neurosurgical Procedures; Paresis; Spinal Puncture; Subarachnoid Space; Tomography, X-Ray Computed; Ventriculostomy

A 59-year-old man with a long history of under-treated diabetes mellitus presented with severe inflammation that had spread from the sinus to the left orbital cavity. The bilateral internal carotid arteries were severely stenotic, causing multiple infarctions in the brain parenchyma. There was no β-D-glucan detected in the cerebrospinal fluid. Based on the presence of central nervous system (CNS) inflammation and vascular involvements that spread from the sinusitis, we tentatively diagnosed this patient as having invasive fungal CNS infection, i.e. zygomycosis or aspergillosis. Although the patient was treated with anti-fungal drugs such as liposomal amphotericin B and voriconazole, he died of respiratory failure. Pathological examination of the autopsied tissues demonstrated zygomycosis in the brain and heart. The prevalence of zygomycosis is generally very low (-5% of CNS infections) compared with that of other fungal infections. The lack of an appropriate diagnostic marker may lead to the under- or mis-diagnosis of zygomycosis. Moreover, it is hard to differentiate zygomycosis from aspergillosis because the two diseases share common clinical features such as the association of sinusitis and vascular involvement. The clinically diagnostic points that discriminate zygomycosis from aspergillosis are as followed; i) β-D-glucan is negative in zygomycosis but positive in aspergillosis; ii) diabetes is more frequent in patients with zygomycosis to those with aspergillosis; iii) the infectious lesion in aspergillosis shows an iso-low-intensity on T(2) weighted MRI image but shows a high intensity lesion in zygomycosis. The mortality rate of CNS zygomycosis is so high that an early diagnosis of it is warranted and the start appropriate anti-fungal treatments or surgical drainage in the early stage of the disease.

Topics: Amphotericin B; Antifungal Agents; Autopsy; Carotid Artery Diseases; Central Nervous System Fungal Infections; Diagnosis, Differential; Humans; Male; Middle Aged; Neuroaspergillosis; Zygomycosis

The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

Topics: Amantadine; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Drug Interactions; Fungi; Itraconazole; Microbial Sensitivity Tests; Naphthalenes; Selegiline; Terbinafine; Valproic Acid

We report the first case of fatal brain infection in an Indian farmer caused by Thielavia subthermophila, a dematiaceous thermophilic fungus in the order Sordariales, and present a review of previous infections from this order. The patient failed amphotericin B therapy combined with surgical excision despite the drug's low MICs in vitro.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Debridement; DNA, Fungal; DNA, Ribosomal Spacer; Fatal Outcome; Humans; India; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Phylogeny; Sequence Analysis, DNA; Sordariales

A case of a 38-year-old male farmer with a brain abscess caused by Cladophialophora bantiana is described. He had a 2 year history of non-insulin-dependent diabetes and myelodysplastic syndrome. A cranial computed tomography scan demonstrated a hypodense ring lesion with peripheral oedema and a midline shift in the left frontal lobe. A darkly pigmented mould was isolated from the brain abscess. The isolate was identified as C. bantiana based on its morphological features and DNA sequence analysis. The patient was unresponsive to burr hole aspiration and irrigation, as well as liposomal amphotericin B infusion, and died after discharge from the hospital. This is believed to be the first case of a cerebral abscess due to C. bantiana in China.

Topics: Adult; Amphotericin B; Antifungal Agents; Ascomycota; Brain Abscess; Central Nervous System Fungal Infections; China; Cladosporium; Diabetes Mellitus, Type 2; Fatal Outcome; Humans; Male; Molecular Sequence Data; Myelodysplastic Syndromes

Topics: Adult; Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Female; Humans; Paracoccidioidomycosis; Tomography, X-Ray Computed

To describe ocular involvement and response to treatment in a patient with human immunodeficiency virus (HIV) infection with severe progressive disseminated histoplasmosis (PDH).. We report a 35-year-old HIV-infected patient seen in our clinics over a period of 4 years. During antiretroviral treatment (ART), the HIV load became undetectable at 3 months; however, CD4 T-cell count increased slowly and rose to 100 cells/microl. Histoplasma capsulatum was cultured from skin pustules, cerebrospinal fluid (CF) and aqueous humour.. The patient developed central nervous system (CNS) involvement 2 months and panuveitis in both eyes 4 months after the initiation of ART. With intravenous liposomal amphotericin B followed by oral voricanozole, the chorioretinal lesions of the right eye (RE) became inactivated and magnetic resonance imaging (MRI) lesions of CNS disappeared. Relapse of the inflammation in the anterior segment of the left eye (LE) resulted in a total closure of the chamber angle and severe glaucoma. Despite medical therapy, two cyclophotocoagulations, total vitrectomy and repeated intravitreal amphotericin B injections, LE became blind. Histoplasma capsulatum was cultured from the aqueous humour after antifungal therapy of 16 months' duration.. PDH with intraocular and CNS manifestations was probably manifested by an enhanced immune response against a previous subclinical disseminated infection. It seems difficult to eradicate H. capsulatum from the anterior segment of the eye in an immunocompromised patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Aqueous Humor; CD4 Lymphocyte Count; Central Nervous System Fungal Infections; Cerebrospinal Fluid; Dermatomycoses; Drug Therapy, Combination; Eye Infections, Fungal; Female; Glaucoma, Angle-Closure; Histoplasma; Histoplasmosis; HIV-1; Humans; Magnetic Resonance Imaging; Panuveitis; Skin; Viral Load

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Diagnostic Errors; Epiglottis; Female; Granuloma; Histoplasmosis; Humans; Middle Aged; Recurrence; Spinal Cord; Tuberculosis, Meningeal

Topics: Adult; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Humans; Injections, Intralesional; Male; Paracoccidioides; Paracoccidioidomycosis; Thalamus

Nervous system infections by Cryptococcus neoformans may occur not only in congenital or acquired immunodeficiency syndromes, but also in immunocompetent hosts. Neurological manifestations of C. neoformans infection include meningitis and, less commonly, parenchymal CNS granulomatous disease. This paper provides detailed clinical descriptions of highly unusual neurological manifestations of cryptococcal nervous system infections. Medical records and diagnostic data including magnetic resonance imaging, histopathology, serology, and CSF analysis were reviewed. A conus medullaris abscess was found in a patient infected with the human immunodeficiency virus (HIV). A patient with Hodgkin's disease was diagnosed with cryptococcal meningitis and dermatitis mimicking ophthalmic zoster. An immunocompetent patient presented with recurrent cerebral infarctions in the setting of cryptococcal meningitis. Cryptococcal infections of the nervous system can cause severe neurological disability when diagnosis is delayed. Sensitive and specific tests are readily available and should be considered when an unusual clinical presentation is encountered.

Topics: Abscess; Adult; Aged; Amphotericin B; Anticoagulants; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Cryptococcosis; Cryptococcus neoformans; HIV Infections; Hodgkin Disease; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Spinal Diseases; Tomography, X-Ray Computed; Warfarin

Primary cerebral phaeohyphomycosis is caused by pigmented fungi that exhibit distinct neurotropism often in immunocompetent individuals. A 20-yr-old male presented with multiple brain abscess which was subsequently proven microbiologically to be due to Cladophialophora Bantiana. In spite of near total excision and appropriate antifungal agents succumbed to his illness. We report this case to highlight its rarity and high mortality in an immunocompetent host. There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation.

Topics: Adult; Amphotericin B; Antifungal Agents; Ascomycota; Brain Abscess; Central Nervous System Fungal Infections; Cladosporium; Craniotomy; Drug Therapy, Combination; Fatal Outcome; Flucytosine; Humans; Itraconazole; Male

Cerebral mucormycosis without rhino-orbital or systemic involvement is an extremely rare condition mostly associated with parenteral drug abuse.. We report the case of a 42-year-old woman who presented with hemiparesis of the left side and altered mental status. Neuroradiologic workup demonstrated an inflammatory lesion involving the right basal ganglia. Proton magnetic resonance spectroscopy demonstrated features consistent with a pyogenic abscess. Computed tomography-guided stereotactic biopsy led to the diagnosis of cerebral mucormycosis. Parenteral AMB-L treatment was conducted, but the patient worsened clinically, presenting with a complete hemiplegia, and cerebral magnetic resonance imaging (MRI) scans demonstrated a voluminous abscess formation. Then, under stereotactic guidance, a surgical endoscopic debridement of the abscess cavity associated with the placement of an Ommaya reservoir was performed. Systemic and intralesional treatment with AmB associated with an adjunctive immune therapy was conducted. At 3-year follow-up, the patient had recovered partially from her left hemiplegia, allowing her to walk without help, and cerebral MRI scans showed complete resorption of the abscess.. Our good results suggest that surgical endoscopic debridement associated with intravenous and intracavitary antifungal therapy might be valuable in treating voluminous deep-seated mucormycotic lesions.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System Fungal Infections; Debridement; Endoscopy; Female; Humans; Mucormycosis

We report 2 pediatric cases of cerebral fungal infection. A patient with severe aplastic anemia developed an Aspergillus species brain abscess and pulmonary aspergillosis after peripheral blood stem cell transplantation. Despite administration of micafungin, amphotericin B, and flucytosine, the patient died 2 months after the transplantation because of underlying pulmonary aspergillosis. Another patient with acute myelogenous leukemia developed a huge brain abscess with histopathologic findings suspicious of mucormycosis. This patient was cured with combination therapy of antifungal agents and intensive surgery, without sequelae. It is important to perform aggressive multimodality treatment, when indicated, including surgical intervention, even if in myelosuppression.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Central Nervous System Fungal Infections; Child; Drug Combinations; Echinocandins; Fatal Outcome; Female; Flucytosine; Follow-Up Studies; Graft Rejection; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Magnetic Resonance Imaging; Male; Micafungin; Mucormycosis; Peripheral Blood Stem Cell Transplantation; Remission Induction; Treatment Outcome

We present a case of cerebral zygomycosis that did not respond to standard treatment with amphotericin B or amphotericin B lipid complex. The patient was eventually cured through a combination of surgery and the use of high dose liposomal amphotericin B. Since penetration of the central nervous system by amphotericin B is poor the application of high dose therapy may be useful in cases of cerebral zygomycosis.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Combined Modality Therapy; Humans; Male; Middle Aged; Zygomycosis

Cryptococcal infections of the CNS are infrequent in immunocompetent hosts. When present, they usually present as meningitis and hydrocephalus or as fungal masses called cryptococcomas. We report a case in which intraventricular cryptococcal cysts clinically and radiologically simulated the racemose form of neurocysticercosis.. A 23-year-old man presented to the emergency department with a 1-week history of severe headache, dizziness, nausea, vomiting, and some lethargy. A computed tomography scan revealed significant hydrocephalus. The patient was admitted to the hospital and immediately underwent a right ventriculostomy tube placement. CSF examination showed a meningitic pattern. Magnetic resonance imaging, including FLAIR images, showed multiple large cysts in the temporal horns of both lateral ventricles in addition to hydrocephalus. When an endoscopic left temporal cyst fenestration failed to decompress his trapped right temporal horn, he underwent placement of a left lateral ventricle to peritoneal shunt and a right temporal cyst to peritoneal shunt. ELISA test results for HIV-1 and -2 antibodies in the patient's serum were negative. His CD4 and CD8 counts were within normal limits. Multiple tests for CSF anticysticercal antibody using IgG ELISA gave unequivocally negative results. Latex agglutination tests detected Cryptococcus neoformans antigen in his CSF in titers of 1:1024, which progressively decreased in response to antifungal therapy. The patient underwent treatment with IV amphotericin B for 7 weeks, IV 5-FC for 2 weeks, and oral fluconazole for 5 weeks. At discharge, 3 consecutive CSF cultures were negative for bacteria and fungi. His neurologic status returned to baseline.. Cryptococcal CNS infections in immunocompetent hosts can mimic the intraventricular form of racemose neurocysticercosis. Distinguishing between the two is essential because the medical management of the 2 conditions is distinct from each other.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Central Nervous System Cysts; Central Nervous System Fungal Infections; Cerebral Ventricles; Combined Modality Therapy; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Neurocysticercosis; Neurosurgical Procedures; Tomography, X-Ray Computed; Ventriculoperitoneal Shunt; Ventriculostomy

Ramichloridium mackenziei is a dematiaceous fungus that usually causes cerebral phaeohyphomycosis. We describe the aspiration cytology findings of a case of cerebral abscess caused by R. mackenziei in a 66-yr-old Saudi woman who had a long standing history of diabetes mellitus and a recent diagnosis of systemic lupus erythematosus. She was on long-term corticosteroid therapy. The patient developed rapidly progressive multiple brain abscesses and died despite aspiration of the abscess and administration of intravenous amphotericin B lipid complex and voriconazole.

Topics: Aged; Amphotericin B; Antifungal Agents; Ascomycota; Biopsy, Needle; Brain Abscess; Central Nervous System Fungal Infections; Combined Modality Therapy; Diabetes Complications; Diabetes Mellitus; Fatal Outcome; Female; Humans; Lupus Erythematosus, Systemic; Pyrimidines; Triazoles; Voriconazole

Blastomycosis is a chronic systemic fungal infection characteristically affecting the skin and lungs. Involvement of the central nervous system (CNS) is unusual, with cases generally presenting with meningitis, and rarely as intracranial mass lesion and solitary or multiple abscesses. Only two cases of intracranial extra-axial blastomycosis have been reported from India, and we report the third case, which presented as meningioma in a 23-year old female.

Topics: Adult; Amphotericin B; Antifungal Agents; Blastomycosis; Brain; Central Nervous System Fungal Infections; Craniotomy; Diagnosis, Differential; Female; Head; Humans; India; Magnetic Resonance Imaging; Meningioma; Radiography

Central nervous system involvement in infection with Blastomyces dermatitidis is uncommon, except in immunocompromised patients. We report a case of central nervous system blastomycosis occurring 18 months after treatment of pulmonary blastomycosis in an immunocompetent child. Our patient was successfully treated sequentially with liposomal amphotericin B followed by oral voriconazole without need for surgical resection.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Blastomyces; Blastomycosis; Central Nervous System Fungal Infections; Drug Administration Schedule; Humans; Immunocompetence; Male; Pyrimidines; Recurrence; Treatment Outcome; Triazoles; Voriconazole

We report on a 10-year-old girl with severe aplastic anaemia who developed rhinocerebral infection caused by Absidia corymbifera and a possible co-infection caused by Alternaria alternata. Despite prolonged neutropenia, therapy with liposomal amphotericin B and posaconazole improved the clinical condition. Subsequently, the girl underwent allogeneic haematopoietic stem cell transplantation (HSCT) for the underlying disease, but the fungal infection remained under control with the antifungal treatment. No severe side effect of the antifungal drugs was noted. Unfortunately, the girl died 5 months after HSCT due to disseminated adenovirus infection.

Topics: Absidia; Alternaria; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Central Nervous System Fungal Infections; Child; Female; Humans; Radiography; Sinusitis; Stem Cell Transplantation; Telencephalon; Transplantation, Homologous; Triazoles; Zygomycosis

Topics: Adult; Amphotericin B; Antifungal Agents; Benzoates; Brain Stem; Caspofungin; Cavernous Sinus; Central Nervous System Fungal Infections; Deferasirox; Diabetic Ketoacidosis; Drug Therapy, Combination; Echinocandins; Humans; Iron Chelating Agents; Lipopeptides; Magnetic Resonance Imaging; Male; Mucormycosis; Nose Diseases; Peptides, Cyclic; Salvage Therapy; Triazoles

We report a patient with a history of prostate cancer and multiple myeloma, with a solitary indolent intracerebral mass lesion without any constitutional symptoms and minimal neurologic symptoms. The radiographic appearance of the lesion was that of a tumor but resection revealed a mycetoma, consistent with Aspergillus. A brief review of the literature discusses the rarity, presentation, diagnosis, and management of primary intracerebral mycetomas.

Topics: Aged; Amphotericin B; Antifungal Agents; Brain Neoplasms; Central Nervous System Fungal Infections; Diagnosis, Differential; Humans; Itraconazole; Magnetic Resonance Imaging; Male; Mitosporic Fungi; Multiple Myeloma; Mycetoma; Neoplasm Metastasis; Prostatic Neoplasms; Treatment Outcome

Currently, few options exist to treat central nervous system (CNS) aspergillosis, which is usually fatal. We tested the efficacy of Abelcet and caspofungin, alone and in combination for treatment of this disease.. Male CD-1 mice were immunosuppressed with 200 mg/kg cyclophosphamide 2 days prior to infection and every 5 days thereafter. In the first study, mice were infected intracerebrally with 2.1 x 10(6) conidia/mouse of Aspergillus fumigatus; 10 days of once daily therapy began one day later. Groups of 10 received 0.8, 4, or 8 mg/kg of Abelcet, intravenously (iv), or caspofungin, intraperitoneally, 0.8 mg/kg of conventional amphotericin B (AmB) iv, or no treatment. In a second study, mice were challenged with 6.4 x 10(6) conidia and given no treatment, 8 mg/kg of Abelcet or caspofungin, alone or in combination. On day 14, cfu were determined in survivors by plating of organ homogenates.. In the first study, mice given any regimen of Abelcet or caspofungin had a survival rate > or =80% whereas untreated had 90% mortality. All drug regimens prolonged survival (P < or = 0.0008) and reduced cfu (P < or = 0.0001-0.003) recovered from the brains and kidneys compared with untreated. Abelcet showed an apparent dose-related reduction of cfu in the brains. Abelcet at 4 or 8 mg/kg were equivalent to AmB in reducing cfu from both organs (P > 0.05); AmB was superior to 0.8 mg/kg of Abelcet in the brain only (P < 0.02). Abelcet at 8 mg/kg or AmB at 0.8 mg/kg were superior to all regimens of caspofungin in reducing cfu (P < or = 0.05-0.001). In the second study, Abelcet alone significantly prolonged survival and reduced cfu in the organs versus the controls. Caspofungin did not significantly prolong survival or reduce cfu in comparison with the controls. In combination, Abelcet and caspofungin were equivalent to Abelcet alone.. Abelcet proved to be efficacious, but not curative, in the treatment of CNS aspergillosis and was equivalent overall to conventional AmB. Caspofungin was not as effective against the larger inoculum, but did not enhance or interfere with the efficacy of Abelcet. Since Abelcet displayed dose-responsive efficacy, it is possible higher doses could produce superior results, yet not show toxicity.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Caspofungin; Central Nervous System Fungal Infections; Drug Combinations; Drug Therapy, Combination; Echinocandins; Lipopeptides; Male; Mice; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols

Cryptococcosis is the third most common deep fungal infection in China and has not yet been reported to be associated with HIV infection there. We report the management of non-HIV-related cryptococcosis, including cutaneous cryptococcosis, pulmonary cryptococcosis and cryptococcal infection of central nervous system (CNS). Establishment of the diagnosis of cutaneous cryptococcosis and pulmonary cryptococcosis were mainly based on the histopathologic examination and mycologic culture, with CNS cryptococcal infection based on mycologic examination and latex agglutination test on cerebrospinal fluid. The treatment of cutaneous cryptococcosis included systemic administration of amphotericin B (AMB), 5-flucytosine and triazole agents such as fluconazole and itraconazole combined with topical ketoconazole cream. Treatment of pulmonary cryptococcosis included systemic use of antifungal medication combined with surgical removal of pulmonary lesions. The treatment of CNS cryptococcal infection was challenging. In this study, 53 patients with CNS cryptococcal infection were divided into three groups according to the antifungal regimens applied: eight patients (group I) received intravenous AMB alone or in combination with 5-flucytosine, five patients (group II) received intravenous fluconazole alone or with 5-flucytosine, and 40 patients (group III) received a two-phase therapy, active therapy and consolidation therapy. In active therapy, the patients received intrathecal and intravenous administration of AMB alone or with 5-flucytosine until the mycological culture of cerebrospinal fluid (CSF) became negative. Consolidation therapy followed active therapy by continuous use of oral fluconazole or itraconazole until direct microscopic examination of CSF was negative for three consecutive weeks. In group I, five patients were cured, two improved, one died and one had relapse. In group II, two patients were cured, one improved and two died. In group III, thirty-nine out of forty patients were cured without recurrence. These results indicate that the two-phase protocol was more desirable for the treatment of non-HIV associated cryptococcal infection of CNS.

Topics: Administration, Oral; Adolescent; Adult; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Child; Child, Preschool; China; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Injections, Intravenous; Injections, Spinal; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged; Retrospective Studies; Skin Diseases; Treatment Outcome; Triazoles

Central nervous system (CNS) aspergillosis is a severe disease that responds poorly to current therapies. The current studies examined the efficacies of several antifungal agents alone or in combination with a murine model of CNS aspergillosis. Immunosuppressed mice were infected intracerebrally with Aspergillus fumigatus and treated with an amphotericin B preparation, an echinocandin, or voriconazole (VCZ) given alone or in combination. Monotherapy studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences, Inc.) were efficacious. However, doses of AmBi above 15 mg/kg of body weight showed reduced efficacy. Neither MICA nor CAS showed dose responsiveness at the doses tested (1, 5, or 10 mg/kg). Only the 40-mg/kg dose of VCZ was effective. AmBi and ABLC showed dose responsiveness, with 10-mg/kg doses causing a significant reduction in fungal burden; they had equivalent activities at the 10-mg/kg dose. Suboptimal dosages of AmBi in combination with MICA, CAS, or VCZ were effective in prolonging survival. However, significantly enhanced activity was demonstrated only with AmBi and VCZ in combination. AmBi in combination with MICA or CAS showed a trend toward enhanced activity, but the combination was not significantly superior to monotherapy. The use of AmBi with CAS or VCZ at optimal doses did not improve efficacy. Cure was not attained with any dosage combinations. These results indicate that AmBi in combination with VCZ may be superior for treatment of CNS aspergillosis; combinations of AmBi and MICA or CAS were not antagonistic and may have a slight benefit.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Caspofungin; Central Nervous System Fungal Infections; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Echinocandins; Lipopeptides; Lipoproteins; Liposomes; Micafungin; Mice; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Mucormycosis is a rare fungal infection that can involve the sino-orbito-cerebral region. Sino-orbito-cerebral mucormycosis is most common in patients who are immunocompromised or have diabetes mellitus, severe malnutrition or burns. This condition can be fatal if it is not diagnosed early and treated aggressively. This article presents 4 cases of mucormycosis, including 2 with orbital apex syndrome, 1 with cavernous sinus syndrome, and 1 with multiple cranial nerve involvement. All of the patients were presented with painful ophthalmoplegia. The predisposing factors for mucormycosis included diabetes mellitus (three patients) and chronic leukemia (one patient). In all cases, mucormycosis was diagnosed by examining endoscopic sinus drainage material and was treated with surgical debridement and amphotericin B. Two patients with central nervous system involvement died. The others have survived, but still exhibiting various neurologic abnormalities after aggressive treatment. Patients with mucormycosis rarely present with orbital apex syndrome. The possibility of mucormycosis should be investigated in any patient with painful ophthalmoplegia, and prompt otorhinolaryngologic examination is recommended to ensure rapid diagnosis and treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Cavernous Sinus; Central Nervous System Fungal Infections; Chronic Disease; Cranial Nerve Diseases; Debridement; Diabetes Complications; Female; Humans; Leukemia; Male; Middle Aged; Mucormycosis; Ophthalmoplegia; Orbital Diseases

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Topics: Adult; Age Distribution; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Cause of Death; Central Nervous System Fungal Infections; Critical Illness; Female; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Neuroaspergillosis; Opportunistic Infections; Retrospective Studies; Risk Assessment; Sex Distribution; Survival Analysis; Thailand

Human central nervous system (CNS) aspergillosis has >90% mortality. We compared posaconazole with other antifungals for efficacy against murine CNS aspergillosis. All tested regimens of posaconazole were equivalent to those of amphotericin B and superior in prolonging survival and reducing CFU to those of itraconazole and caspofungin and to vehicle controls. No antifungal regimen effected cure. No toxicity was noted. Overall, posaconazole shows potential for treating CNS aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Central Nervous System Fungal Infections; Male; Mice; Survival; Survival Analysis; Triazoles

The outcome of central nervous system (CNS) histoplasmosis is often unfavorable. Although fluconazole plays an integral role in treatment of fungal meningitis, its role in the treatment of histoplasmosis is hampered by reduced activity and potential development of resistance. A murine model of CNS histoplasmosis was used to evaluate the hypothesis that a combination of amphotericin B and fluconazole therapy would be superior to amphotericin B monotherapy. Groups of B6C3F(1) mice were infected by injection of Histoplasma capsulatum into the subarachnoid space. The addition of fluconazole hindered the antifungal effect of amphotericin B, as determined by measurement of fungal burden, suggesting antagonism in the brain. Fluconazole was less effective as a single agent than was amphotericin B, despite the greater penetration of fluconazole into brain tissues. The hypothesis that amphotericin B-fluconazole combination therapy would be superior to amphotericin B monotherapy for treatment of CNS histoplasmosis was not supported by this study.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Disease Models, Animal; Drug Therapy, Combination; Female; Fluconazole; Histoplasmosis; Mice; Spleen

Cryptococcal infection is common in immunocompromised patients, often presenting with meningitis or meningoencephalitis. We report an unusual presentation of cryptococcal infection in an immunocompetent patient presenting with headache and hemiplegia. CT demonstrated a large ring-enhancing lesion in the parietal region with intralesional calcification.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Cryptococcosis; Follow-Up Studies; Humans; Male; Parietal Lobe; Tomography, X-Ray Computed

This is the first reported case of cerebral blastomycosis successfully treated with amphotericin B lipid complex.

Topics: Adult; Amphotericin B; Antifungal Agents; Blastomycosis; Central Nervous System Fungal Infections; Cerebellar Diseases; Drug Combinations; Female; Humans; Itraconazole; Phosphatidylcholines; Phosphatidylglycerols; Recurrence

Of the 21 patients with aspergillosis of central nervous system seen during the years 1990-1997, 16 (76%) had aspergillosis of sino-cranial origin. The occupation in patients with sino-cranial aspergillosis was either agricultural or manual work and predisposing risk factors were present in only two (12.5%) patients. Skull-base syndromes were the presenting features in 13 patients and three patients presented with features of intracranial space-occupying lesion. Paranasal sinus mass lesions were seen in all the 16 patients. Computerized tomography showed intracranial extradural-enhancing mass lesions in the anterior, middle or posterior cranial fossa in nine (68%) patients, intracranial and orbital lesions in four and orbital lesions in three. Well-formed granuloma with dense fibrosis was the histological feature. Survival rates were not good even after surgical and antifungal chemotherapy. Surgical treatment was subradical in our series. The majority of cases of sinocranial aspergillosis are reported from countries with temperate climates and the high incidence in these regions is probably related to constant exposure to the high spore content of pathogenic Aspergillus species in the 'mouldy' work environment.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Biopsy; Brain Diseases; Central Nervous System Fungal Infections; Climate; Female; Flucytosine; Granuloma; Humans; India; Male; Middle Aged; Occupational Diseases; Orbital Diseases; Risk Factors; Sinusitis; Tomography, X-Ray Computed

Because the neurotoxic effects of the antifungal drug amphotericin B (AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes. AMB caused a dose-dependent increase of NO generation in interferon-gamma (IFN-gamma)-stimulated rat and mouse astrocytes, as well as in IFN-gamma + tumor necrosis factor-alpha (TNF-alpha)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor IRF-1. The activation of transcription factor NF-kappaB was apparently required for AMB-induced iNOS mRNA expression, as the latter was abolished by NF-kappaB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-gamma + AMB treatment led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity toward IFN-gamma-stimulated astrocytes was dependent on both AMB and NO action, since AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial dysfunction. These results suggest that the enhancement of cytokine-induced iNOS activation in astrocytes and the subsequent release of high amounts of NO might be at least partly responsible for AMB neurotoxicity.

Topics: Amphotericin B; Animals; Animals, Newborn; Antifungal Agents; Astrocytes; Cell Respiration; Central Nervous System Fungal Infections; DNA-Binding Proteins; Drug Interactions; Enzyme Inhibitors; Interferon Regulatory Factor-1; Interferon-gamma; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Mice; Mitochondria; Nerve Degeneration; Neurotoxins; NF-kappa B; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Phosphoproteins; Rats; RNA, Messenger; Sialoglycoproteins; Transcription, Genetic; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

We report the first documented case of brain abscess due to the dematiaceous fungus Microascus cinereus, an organism common in soil and stored grain. M. cinereus was isolated from brain abscess material from a bone marrow transplant recipient. The patient responded well to treatment by amphotericin B lipid complex, itraconazole, and a craniotomy but later died from secondary complications caused by graft-versus-host disease.

Topics: Adult; Amphotericin B; Ascomycota; Bone Marrow Transplantation; Brain Abscess; Central Nervous System Fungal Infections; Craniotomy; Drug Combinations; Female; Graft vs Host Disease; Humans; Itraconazole; Phosphatidylcholines; Phosphatidylglycerols

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Central Nervous System Fungal Infections; Drug Therapy, Combination; Fluconazole; Follow-Up Studies; Homosexuality, Male; Humans; Male; Pneumonia, Pneumocystis; Spinal Puncture; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Ramichloridium obovoideum ("Ramichloridium makenziei") is a rare cause of lethal cerebral phaeohyphomycosis. It has been, so far, geographically restricted to the Middle East. BALB/c mice were inoculated with two strains of R. obovoideum intracranially. Therapy with amphotericin B, itraconazole, or the investigational triazole SCH 56592 was conducted for 10 days. Half the mice were monitored for survival and half were killed for determination of the fungal load in brain tissue. Recipients of SCH 56592 had significantly prolonged survival and lower brain fungal burden, and this result was found for mice infected with both of the fungal strains tested. Itraconazole reduced the brain fungal load in mice infected with one strain but not the other, while amphotericin B had no effect on brain fungal concentrations. This study indicates a possible role of SCH 56592 in the treatment of the serious cerebral phaeohyphomycosis due to R. obovoideum.

Topics: Amphotericin B; Animals; Antifungal Agents; Ascomycota; Central Nervous System Fungal Infections; Disease Models, Animal; Female; Itraconazole; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mycoses; Triazoles

The central nervous system (CNS) distribution and antifungal efficacy of all 4 approved formulations of amphotericin B (AmB) were investigated in a rabbit model of hematogenous Candida albicans meningoencephalitis. Treatment with AmB deoxycholate (1 mg/kg/day) or liposomal AmB (5 mg/kg/day) yielded the highest peak plasma concentration (C(max)), area under concentration versus time curve from zero to 24 h (AUC(0-24)), and time during dosing level tau Ttau>minimum inhibitory complex (MIC) values and led to complete eradication of C. albicans from brain tissue (P<.05 vs. untreated controls). By comparison, AmB colloidal dispersion and AmB lipid complex (5 mg/kg/day each) were only partially effective (not significant vs. untreated controls). There was a strong correlation of C(max), AUC(0-24), C(max)/MIC, AUC(0-24)/MIC, and Ttau>MIC with clearance of C. albicans from brain tissue (P

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Central Nervous System Fungal Infections; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Delivery Systems; Female; Lipids; Microbial Sensitivity Tests; Rabbits; Treatment Outcome