amphotericin-b and Central-Nervous-System-Diseases

Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Endocarditis; Histoplasmosis; Humans; Lung Diseases, Fungal; Mediastinitis

Topics: Amphotericin B; Candidiasis; Central Nervous System Diseases; Cross Infection; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Prognosis

Topics: Amphotericin B; Antifungal Agents; Antimalarials; Antiprotozoal Agents; Antitrichomonal Agents; Central Nervous System Diseases; Chloroquine; Humans; Mefloquine; Metronidazole; Quinine

We report a fatal case of invasive pulmonary aspergillosis in a severely ill neonate and review 43 additional cases of invasive aspergillosis reported from 1955 through 1996 that occurred during the first 3 months of life. Eleven of the 44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary aspergillosis, and 14 had disseminated disease. Most infections were nosocomial in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections (23%) accounted for the majority of underlying conditions. At least 41% of the patients had received corticosteroid therapy before diagnosis, but only one patient had been neutropenic. Among patients who received medical and/or surgical treatment, outcome was relatively favorable, with an overall survival rate of 73%. Invasive aspergillosis may occur in neonates and young infants and warrants consideration under certain circumstances. Current therapeutic approaches consist of high-dose amphotericin B and appropriate surgical interventions.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Central Nervous System Diseases; Critical Illness; Cross Infection; Dermatomycoses; Fatal Outcome; Gastrointestinal Diseases; Humans; Infant; Infant, Newborn; Lung Diseases; Male

Cerebral and cerebellar masses occurred in patients with paracoccidioidomycosis. Correct diagnosis was delayed due to overlooking the abnormal lung roentgenograms and the history of previous disease in a different localization. The fungus was identified through biopsy and direct examination of the samples. In two patients necropsy confirmed the diagnosis. None of the patients responded to amphotericin B or cotrimoxazole. A 10 year English and Latin American literature review on neuroparacoccidioidomycosis was performed through a MEDLINE and LILACS (Latin American Literature Search System) data base systems.

Topics: Amphotericin B; Central Nervous System Diseases; Humans; Male; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Eye Infections, Fungal; Fluconazole; Humans; Lung Diseases, Fungal; Male; Prostatic Diseases

Topics: Adolescent; Adult; Africa; Amphotericin B; Asia, Southeastern; Australia; Central Nervous System Diseases; Cryptococcosis; Cytosine; Drug Therapy, Combination; Europe; Female; Flucytosine; Humans; Japan; Male; United States

In the past 20 years, there has been a marked increase in the number of reported cases of meningitis and brain abscess due to fungi and yeasts. This increase is due in part to better diagnostic techniques and greater awareness of the possibility of fungal invasion of the nervous system; but the increase can also be attributed to a growing pool of severely compromised hosts, many of whom are undergoing treatment with adrenal glucocorticoids or immunosuppressive agents. The diagnosis and treatment of aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, infections caused by dematiaceous fungi, histoplasmosis, paracoccidioidomycosis, petriellidosis, and sporotrichosis, as well as relatively rare infections of the central nervous system caused by other fungi, are discussed. The efficacy of amphotericin B and 5-fluorocytosine in the treatment of CNS fungal and yeast infections is also evaluated.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Central Nervous System Diseases; Chromoblastomycosis; Cladosporium; Coccidioidomycosis; Cryptococcosis; Female; Fungi; Histoplasmosis; Humans; Male; Meningitis; Meningoencephalitis; Middle Aged; Mucormycosis; Mycoses; Paracoccidioidomycosis; Phialophora; Sporotrichosis

Blastomycosis is the infection caused by the dimorphic fungus Blastomyces dermatitidis. The fungus was believed to be limited in distribution to North America but is found in Africa and northern South America, too. The exact natural habitat of B. dermatitidis is still uncertain with only rare reported isolation of the fungus from the environment. The inability to recover the organism from nature along with the absence of both a reliable skin test antigen and a sensitive serological test have significantly restricted our understanding of the epidemiology and the full clinical spectrum of blastomycosis. An accidental laboratory infection and several common source epidemics have enabled us to recognize that blastomycosis may be a self-limited pulmonary infection. Endogenous reactivation and opportunistic infections have been newly appreciated as clinical presentations of blastomycosis. This report will review blastomycosis with particular emphasis on these recent developments.

Topics: Adult; Amphotericin B; Animals; Antibodies, Fungal; Arthritis, Infectious; Blastomyces; Blastomycosis; Bone Diseases; Central Nervous System Diseases; Child; Dermatomycoses; Disease Outbreaks; Female; Humans; Lung Diseases, Fungal; Male; United States; Urologic Diseases

The recent development of new antifungal antimicrobials that can be administered in combination with amphotericin B or as alternatives to it has expanded the dimensions of treatment for fungal infections of the central nervous system. These disorders have acquired increasing importance as patients with malignant and other illnesses associated with immunosuppression survive longer and as renal transplantation is more widely applied. Amphotericin B has remained the most effective therapeutic preparation for most types of neurological fungal disease, although important roles for 5-fluorocytosine, miconazole, and, more recently, ketoconazole are being recognized.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Chemical Phenomena; Chemistry; Flucytosine; Humans; Kidney Diseases; Miconazole; Mycoses

Topics: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Burns; Candida albicans; Candidiasis; Catheterization; Central Nervous System Diseases; Diabetes Complications; Diagnosis, Differential; Fluorescent Antibody Technique; Fluorouracil; Hemagglutination Inhibition Tests; Humans; Hydrogen-Ion Concentration; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lung Diseases, Fungal; Nystatin; Pneumonia, Pneumocystis; Pyelonephritis; Respiratory Hypersensitivity; Sepsis; Serologic Tests

Determining the extent of cryptococcal disease (CD) is key to therapeutic management. Treatment with fluconazole is only recommended for localised pulmonary disease. Induction therapy with amphotericin B (AmB) and flucytosine is recommended for disease at other sites, irrespective of central nervous system (CNS) involvement, but this is not often followed in patients without meningitis. In this study, we compared treatment and mortality between patients with CD of the CNS and other extrapulmonary (OE) sites.. This is a retrospective, single-centre study of all hospitalised patients with nonpulmonary cryptococcal infection from 2002 to 2015 who underwent lumbar puncture. Demographics, predisposing factors, comorbidities, clinical presentation, laboratory values, antifungal treatment and mortality data were collected to evaluate 90-day mortality and treatment differences between patients with OE and CNS CD. Survival analysis was performed using multivariable Cox regression analysis.. Of 193 patients analysed, 143 (74%) had CNS CD and 50 (26%) had OE CD. Ninety-day mortality was 23% and similar between the OE and CNS CD groups (22% vs 23%, p = .9). In the comorbidity-adjusted multivariable Cox regression model, mortality risk was similar in the OE and CNS groups. Fewer patients with OE CD received induction therapy with AmB and flucytosine compared to those with CNS disease (28% vs 71.3%, p < .001).. Patients with OE CD had similar 90-day mortality compared to those with CNS disease. Despite current guideline recommendations, patients with OE disease were less likely to receive appropriate induction therapy with AmB and flucytosine compared to patients with CNS disease.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Missouri; Treatment Outcome

Treatment options for Exserohilum rostratum meningoencephalitis and other causes of phaeohyphomycosis of the central nervous system (CNS) are limited, while mortality and morbidity remain high. We therefore evaluated isavuconazole, a new antifungal triazole in comparison to liposomal amphotericin B (LAMB), in vitro and in the rabbit model of Exserohilum rostratum meningoencephalitis. We hypothesized that isavuconazole alone or in combination with LAMB or micafungin may be alternative options for treatment of CNS phaeohyphomycosis. We therefore investigated the in vitro antifungal activity of isavuconazole alone or in combination with amphotericin B deoxycholate (DAMB) or micafungin and efficacy of treatment with isavuconazole and LAMB in a rabbit model of experimental E. rostratum meningoencephalitis. Combination checkerboard plates were used to determine the minimum inhibitory concentrations, minimal lethal concentrations, fractional inhibitory concentration indices, and Bliss surface analysis of isavuconazole and amphotericin B deoxycholate (DAMB), either alone or in combination. As there were no in vitro synergistic or antagonistic interactions for either combination of antifungal agents against the E. rostratum isolates, in vivo studies were conducted with isavuconazole and LAMB as monotherapies. Rabbits were divided in following groups: treated with isavuconazole at 60 mg/kg/d (ISAV60), LAMB at 5.0 (LAMB5), 7.5 (LAMB7.5), and 10 mg/kg/d (LAMB10), and untreated controls (UC). In ISAV60-, LAMB5-, LAMB7.5-, and LAMB10-treated rabbits, significant reductions of fungal burden of E. rostratum in cerebral, cerebellar, and spinal cord tissues (P < 0.01) were demonstrated in comparison to those of UC. These antifungal effects correlated with significant reduction of CSF (1→3)-β-D-glucan levels vs UC (P < 0.05). These data establish new translational insights into treatment of CNS phaeohyphomycosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Ascomycota; Central Nervous System Diseases; Disease Management; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Microbial Sensitivity Tests; Nitriles; Phaeohyphomycosis; Pyridines; Rabbits; Triazoles

Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known.. We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis.. Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline (P = .94 ). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (P = .034), renal failure at baseline (P = .016), and fungemia (P = .003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P = .007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P = .349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P = .047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P = .004 ) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; P = .008).. Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Drug Compounding; Female; Humans; Lipids; Male; Middle Aged; Prospective Studies; Transplants; Treatment Outcome

We report a fatal case of a rhino-cerebral zygomycosis, caused by Rhizopus arrhizus (oryzae). The patient was suffering from idiopathic thrombopenic purpura, diagnosed 1 year earlier. He was already treated with methylprednisolone 5 months prior to his admission to the hospital for a loss of vision and pain in the left eye as well as left orbital cellulitis. After an initial empirical treatment with broad spectrum antibiotics and voriconazole (infection of unknown origin), the patient was treated with liposomal amphotericin as soon as a positive fungal culture revealed a zygomycete. Unfortunately, the mould was resistant to amphotericin B (MIC: 16 microg ml(-1)) and probably to posaconazole (MIC: 4 microg ml(-1)), which was co-administrated a few days later.

Topics: Aged; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Central Nervous System Diseases; Drug Resistance, Fungal; Fatal Outcome; Humans; Male; Methylprednisolone; Purpura, Thrombocytopenic, Idiopathic; Pyrimidines; Rhinitis; Rhizopus; Triazoles; Voriconazole; Zygomycosis

Cryptococcosis is a life-threatening fungal infection among human immunodeficiency virus (HIV)-positive patients and also occurs frequently in HIV-negative patients. A retrospective cohort study was conducted among patients with cryptococcosis. Clinical manifestations, laboratory findings, treatment, and outcomes for 149 HIV-positive and 29 HIV-negative patients were compared. Neurological involvement occurred more frequently in HIV-positive patients (91.9 versus 20.7%, P<0.001), whereas pulmonary involvement was more frequently observed in HIV-negative patients (34.5 versus 2.7%, P<0.001). Ninety percent of HIV-positive patients and 74% of HIV-negative patients had positive serum cryptococcal antigen (P=0.119). HIV-positive patients were more likely to have a cerebrospinal fluid (CSF) preparation that is positive for India ink staining (81 versus 50%, P<0.001) and a CSF cryptococcal antigen titer of > or =1:1,024 (61.1 versus 16.7%, P=0.038). Most of the patients in both groups received amphotericin B as the primary therapy. Cryptococcosis-related mortality was high and did not differ between the two groups (22.2 versus 34.5%, P=0.162). Kaplan-Meier analysis revealed that HIV-positive patients had a higher relapse rate (P=0.011), especially among those lacking antiretroviral therapy. In conclusion, clinical presentation of cryptococcosis among HIV-negative patients varies and differs from that of HIV-positive patients. Awareness and prompt management are crucial for establishing a diagnosis and initiating proper treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antigens, Fungal; Antiretroviral Therapy, Highly Active; Central Nervous System Diseases; Cerebrospinal Fluid; Cohort Studies; Cryptococcosis; Cryptococcus neoformans; Female; HIV Seronegativity; HIV Seropositivity; Humans; Kaplan-Meier Estimate; Lung Diseases, Fungal; Male; Middle Aged; Recurrence; Retrospective Studies; Thailand

Histoplasmosis is an important cause of morbidity and death in HIV-infected patients. Significant developments concerning the diagnosis, treatment, follow-up, and prophylaxis of histoplasmosis are discussed. Itraconazole is highly effective at both inducing and maintaining remission in mild to moderate cases of disseminated histoplasmosis. In cases of moderate to severe disease, amphotericin B remains the therapy of choice. A table presents comparative results of treating mild to moderate disseminated histoplasmosis with the drugs itraconazole versus fluconazole. Currently, no resistance of Histoplasmosis capsulatum to itraconazole has emerged from prolonged therapy. Maintenance therapy for life is recommended for patients with CD4 counts less than 100; however, feasibility studies are evaluating the possibility of its discontinuance. While no prophylaxis recommendations currently exist, patients with CD4 counts less than 100 who are exposed to histoplasmosis are recommended to begin oral itraconazole (200 mg daily).

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Clinical Trials as Topic; Dosage Forms; Fluconazole; Histoplasmosis; Itraconazole; Ketoconazole; Remission Induction

The microbiology, epidemiology, clinical features, and treatment of aspergillosis are discussed. Aspergillosis is a fungal infection that is increasingly found in patients with advanced HIV disease. The lung is involved in almost 75 percent of aspergillus infections. The central nervous system is the second most commonly infected site, occurring in about 10 to 15 percent of reported cases. Sinus involvement is recognized as a feature of aspergillosis, accounting for about 75 percent of all cases of fungal sinusitis seen in AIDS patients. While these infections are more than likely localized, dissemination to many organs can occur. The prognosis of patients with aspergillosis is poor, and its treatment is difficult. Treatment with amphotericin B is considered the gold standard, but responses are limited, with only 20 to 30 percent of patients responding in most cases. Itraconzole is approved as a second-line therapy. Surgery may also be appropriate for some cases of aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Central Nervous System Diseases; HIV Infections; Humans; Itraconazole; Lung Diseases; Sinusitis

Infection is still the most common complication of shunt procedures in children. However, fungal infection is still considered to be rare. We found that fungi accounted for 17% of shunt infections (8 of 48) in a retrospective study. All of the patients were premature babies and had received a ventriculoperitoneal shunt because of hydrocephalus. The clinical manifestations were subtle and insidious. The time of onset of infection ranged from 1 month to 1 year after the insertion of the shunt. Examination of the cerebrospinal fluid of infected patients showed mild pleocytosis with an elevated protein concentration. Candida species (including Candida albicans, Candida parapsilosis, and Candida tropicalis) or Torulopsis glabrata were isolated. In all but one case, shunts were removed and systemic therapy with amphotericin B was administered. Amphotericin B was given intrathecally to two patients, who did not respond to systemic therapy. Treatment with fluconazole failed for one patient. We suggest performing fungal cultures in cases of shunt infection, especially those involving premature infants. Extraventricular drainage, systemic therapy with amphotericin B, and insertion of a new shunt remain the principal components of the treatment regimen for fungal shunt infections in children.

Topics: Amphotericin B; Candidiasis; Central Nervous System Diseases; Female; Humans; Hydrocephalus; Infant; Infant, Newborn; Infant, Premature; Injections, Intravenous; Injections, Spinal; Male; Retrospective Studies; Ventriculoperitoneal Shunt

Eleven patients with CNS cryptococcal infection are reviewed. The most prominent symptom was headache, present in all patients. The clinical manifestations were the direct result of the meningitis itself or a consequence of intracranial cryptococcal granulomata or hydrocephalus, these latter 2 complications being demonstrable on CT head scan. In the 2 patients who also had MRI scans, additional parenchymal lesions were revealed which had not been detected by CT. Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice, but in 3 patients fluconazole was also used. Chronic oral therapy with this agent has maintained a good clinical response in one patient who failed to respond to traditional antifungal therapy.

Topics: Adult; Aged; Amphotericin B; Central Nervous System Diseases; Cryptococcosis; Female; Fluconazole; Flucytosine; Humans; Male; Middle Aged; Tomography, X-Ray Computed

Thirty-five cases of cryptococcosis of the central nervous system (CNS) were studied, 17 of them submitted to renal transplantation. The objective was to evaluate the therapeutic responses observed in the group of kidney transplant patients with CNS cryptococcosis. They were submitted to amphotericin B therapy, with emphasis to the renal function. The results in this group were compared with the outcome in the group of patients with the same infection, submitted to the same therapeutic scheme, but without previous impairment of renal function. Among the 35 patients, 20 were male; the age varied between 4 and 76 years. Associated clinical conditions were noticed in 25 patients, 17 of them with renal transplantation. Among 35 patients, 10 died in the first days of the treatment; 25 patients were effectively treated for CNS cryptococcosis, 18 of them with associated clinical conditions; 15 were kidney transplant patients. The drugs used in the treatment of CNS cryptococcosis were, as possible, the amphotericin B by intravenous and intrathecal route (lumbar puncture) associated with 5-fluorocytosine. Seven patients died during the treatment; then, of the 35 patients who were initially evaluated, 17 died and 18 were successfully treated, with a death rate of 48.57%. Various intercurrencies were observed with the use of amphotericin B and 5-fluorocytosine. The clinical and therapeutic results recorded in this study were compared with the information met in literature. The analysis of the results emphasizes the need of the discovery of better and less toxic drugs than those currently used. Amphotericin B still is the most important drug in the treatment of CNS cryptococcosis and the therapeutic scheme currently recommended consists in the association of amphotericin B and 5-fluorocytosine, and there has been also advantage in the simultaneous use of intravenous and intrathecal amphotericin B. Statistical analysis of the results showed that there is no harm with the use of intravenous amphotericin B in renal transplanted patients with cryptococcosis of the central nervous system.

Topics: Adolescent; Adult; Aged; Amphotericin B; Central Nervous System Diseases; Child; Child, Preschool; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Prognosis; Retrospective Studies

Involvement of the central nervous system (CNS) by Histoplasma capsulatum is a rare event. It is usually not included in the differential diagnosis of CNS lesions in patients with acquired immunodeficiency syndrome (AIDS). Herein are described four patients with AIDS and progressive disseminated histoplasmosis who had CNS involvement. Histoplasmosis in the CNS may produce meningitis, single or multiple brain abscesses, and may present with either a clinical picture of obtundation or a deteriorating space-occupying CNS lesion. Three of the four patients were treated with amphotericin B and had initial clinical response, but ultimately, all experienced a relapse and died from their infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Central Nervous System Diseases; Histoplasmosis; Humans; Male

The pathogenesis, clinical signs and symptoms, laboratory manifestations, and laboratory diagnosis of cryptococcal infection of the central nervous system are reviewed, as well as the interaction between the organism and the immune system of the host. In addition, based on our own experience and that of others, the therapy and prognosis of cryptococcal meningitis are discussed.

Topics: Amphotericin B; Central Nervous System Diseases; Cryptococcosis; Flucytosine; Humans; Meningitis; Prognosis

The clinical and pathologic findings in 32 patients with central nervous system (CNS) coccidioidomycosis were studied. Seventeen patients had received more than 1.5 g of amphotericin B (AMB), chiefly intravenously, during treatment periods of up to eight years. Eight patients had received 246 mg to 1.3 g of AMB, and three patients had received only brief treatment (one to three days; total dose, no more than 100 mg). Fifteen patients had not received AMB. Significant clinical differences between the patients treated with and without AMB were longer survival time following diagnosis of illness (P less than 0.05) and more frequent cranial nerve signs in the treated patients (P = 0.089). The wide spectrum of macroscopic and microscopic lesions in the CNS included meningitis, ventriculitis, hydrocephalus, and cerebritis. Long-standing infections were associated with disseminated discrete foci of gliosis and infarcts in the brain, particularly in the basal ganglia and deep white matter, related to endarteritis obliterans in basilar meninges. In contrast to patients with CNS and systemic mycoses treated with amphotericin B methyl ester (J Infect Dis 146:125, 1982), no diffuse lesions of white matter were found in patients treated with or without AMB. Histopathologic patterns observed in this study included leptomeningitis alone, leptomeningitis with cerebritis, leptomeningitis with cerebritis and infarcts, and the unusual pattern of disseminated miliary granulomas. The frequency and extent of CNS lesions in the groups treated with and without AMB were not significantly different. It is concluded that AMB therapy, while prolonging survival, does not alter the spectrum of pathologic findings in CNS coccidioidomycosis infection.

Topics: Adolescent; Adult; Aged; Amphotericin B; Central Nervous System; Central Nervous System Diseases; Child, Preschool; Coccidioidomycosis; Endarteritis; Female; Humans; Hydrocephalus; Male; Meningitis; Middle Aged

The clinical courses in 27 infants with culture or autopsy evidence of systemic candidiasis were reviewed. Twenty-two infants (group 1) had persistent signs of sepsis and clinical deterioration or died before institution of antifungal therapy. Five infants (group 2) improved markedly before culture results were reported, and recovered without systemic antifungal therapy. Fourteen infants in group 1 (64%) had central nervous system infection. Of four patients in whom CNS involvement was diagnosed only postmortem, antemortem cerebrospinal fluid from three was abnormal despite sterile cultures; no antemortem CSF was obtained in the other. In meningitis caused by susceptible organisms addition of flucytosine sterilized CSF within 5 days, although prior amphotericin monotherapy had been unsuccessful. Of 14 patients in group 1 who received systemic antifungal therapy, only one died with Candida infection. Toxicity from antifungal agents occurred in 11 of 13 successfully treated infants, but was reversible in every case except one by modifying the dosage. Our data indicate that (1) CNS infection is very common in infants with systemic candidiasis, (2) combined flucytosine-amphotericin therapy may facilitate treatment of CNS infection and should be the initial therapy for systemic candidiasis in infants, (3) Gram stains of CSF and urine enhance early diagnosis, (4) isolation of Candida from normally sterile body fluids in high-risk infants should be considered pathogenic and therapy initiated unless the clinical course strongly suggests otherwise, and (5) toxicity from antifungal agents is common but usually reversible.

Topics: Amphotericin B; Candidiasis; Central Nervous System Diseases; Female; Flucytosine; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male

Candida has become the most prevalent cerebral mycosis at autopsy, indicating a significant incidence coupled with inadequate eradication. Of 29 patients with systemic candidiasis, 48 percent (14 of 29) also had central nervous system involvement. Of these patients, however, only 21 percent (three of 14) had antemortem diagnosis, and only one of these three patients remains alive; the two patients with antemortem diagnosis who died had a meningeal form that, although easier to document on the basis of cerebrospinal fluid examination, is now distinctly rarer than other forms of the disease in adults. The lone surviving patient was treated with amphotericin B for endocarditis and mycotic aneurysms of the cerebral vessels. One clue to central nervous system candidal infection was the striking correlation between cardiac and cerebral involvement; 80 percent of patients with myocardial or valve infection also had central nervous system candidiasis. Most forms of immunosuppression represent a risk factor for both the systemic and cerebral mycoses. Neuropathologically, there is a spectrum of disease entities associated with Candida, including two previously unrecognized lesions reported herein: fungus balls of both white and gray matter and mycotic aneurysms secondary to Candida parapsilosis. Other parenchymal presentations include thrombosis, vasculitis, abscess, hemorrhage, and demyelination. For drug therapy such as amphotericin B to be more effective, earlier diagnosis of these parenchymal infections must be sought.

Topics: Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Candidiasis; Central Nervous System Diseases; Female; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged

Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 micrograms/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (+/- SD) was 1.9% +/- 0.8% for ventricular fluid and 5.4% +/- 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Coccidioidomycosis; Drug Therapy, Combination; Humans; Imidazoles; Ketoconazole; Piperazines

Topics: Amphotericin B; Central Nervous System Diseases; Humans; Leukoencephalopathy, Progressive Multifocal

Topics: Amphotericin B; Brain Diseases; Central Nervous System Diseases; Cryptococcosis; Flucytosine; Humans

Results obtained in the treatment of cryptococcosis of the central nervous system with amphotericin-B, 5-fluorocytosine and miconazole are evaluated. The evaluation is based upon 18 cases. Emphasis is given to data pertinent to aspects proper to 7 of them, submitted to chronic immunosuppressive treatment due to previous kidney transplantation. Side effects varied from case to case in the patients submitted to amphotericin-B and 5-fluorocytosine treatment. The intrathecal and the intraventricular administration of amphotericin-B was followed by complications of several types. Miconazole was used in one case. Its intravenous and its intrathecal administration did not provoke remarkable side effects.

Topics: Adolescent; Adult; Amphotericin B; Central Nervous System Diseases; Child, Preschool; Cryptococcosis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Humans; Imidazoles; Injections, Intraventricular; Injections, Spinal; Kidney Transplantation; Male; Miconazole; Middle Aged; Transplantation, Homologous

Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.

Topics: Adolescent; Adult; Amphotericin B; Central Nervous System Diseases; Female; Humans; Kidney Transplantation; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Peritoneal Diseases; Pneumonia; Postoperative Complications; Surgical Wound Infection; Transplantation, Homologous

A case of central nervous system histoplasmosis complicated by obstruction of the fourth ventricle is described. The patient rarely exhibited systemic symtoms of infection despite positive cultures for Histoplasma capsulatum from bone marrow, blood and urine. Infection recurred despite the administration of a total of 5 g of systemic amphotericin B. An additional course combined with intrathecal amphotericin B was terminated because of transverse myelitis.

Topics: Adolescent; Amphotericin B; Central Nervous System Diseases; Histoplasmosis; Humans; Hydrocephalus; Male

Treatment of a transplantable leukemia in AKR mice with both amphotericin B and 1,3-Bis(2-chloroethyl)-1-nitrosourea cured a significant percentage of animals with advanced disease. Some long-term survivors developed paralysis, and they invariably demonstrated central nervous system (CNS) leukemia. Some of these animals had a systemic relapse of their leukemia, and the CNS appeared to act as a focus for systemic dissemination. The occurrence patterns and histopathologic features of the CNS leukemia in the long-term survivors were strikingly similar to those observed in humans with acute lymphoblastic leukemia.

Topics: Amphotericin B; Animals; Brain; Carmustine; Central Nervous System Diseases; Disease Models, Animal; Female; Leukemia, Experimental; Leukemia, Lymphoid; Meninges; Mice; Mice, Inbred AKR; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paralysis; Spinal Cord

Topics: Adult; Amphotericin B; Brain Diseases; Central Nervous System Diseases; Cryptococcosis; Cytosine; Fluorine; Granuloma; Humans; Male; Meningitis; Microscopy, Phase-Contrast; Middle Aged; Spinal Cord Diseases; Temporal Lobe

Topics: Amebiasis; Amebicides; Amoeba; Amphotericin B; Brain; Brain Stem; Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Encephalitis; Humans; Leukocyte Count; Lymphocytosis; Male; Middle Aged; Necrosis; Temporal Lobe; Water Pollution

Topics: Amphotericin B; Candida albicans; Candidiasis; Candidiasis, Oral; Central Nervous System Diseases; Culture Media; Digestive System; Female; Gastroenteritis; Gentian Violet; Humans; Infant, Newborn; Mustard Compounds; Nystatin; Urinary Tract Infections

Topics: Adolescent; Adult; Age Factors; Aged; Amphotericin B; Central Nervous System Diseases; Child; Cryptococcosis; Cryptococcus; Female; Humans; Leukocyte Count; Lung Diseases, Fungal; Male; Middle Aged; Neurologic Manifestations; Sex Factors

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Amphotericin B; Anti-Bacterial Agents; Candida; Central Nervous System; Central Nervous System Diseases; Child; Humans

Topics: Adult; Amphotericin B; Blepharoptosis; Blindness; Central Nervous System Diseases; Chronic Disease; Diabetes Complications; Follow-Up Studies; Fungi; Humans; Male; Mycoses; Ophthalmoplegia; Orbit

Topics: Adult; Amphotericin B; Central Nervous System Diseases; Cryptococcosis; Humans; Male

(1) A survey of cryptococcal infections of the nervous system in Queensland, Australia, revealed the nine year prevalence rate for the Australian aboriginal to be some 17 times greater than that of the white population. Uncommon in the first decade of life, the disease was developed by 79% of 29 patients between 20 and 59 years, males being affected twice as commonly as females. (2) Cryptococcosis appears to be more common in Australia than in the United Kingdom, and in Queensland the nine year incidence of neurological cryptococcosis was 4·7 per 100,000 in the tropical north compared with 1·8 per 100,000 in the southern parts of the State. Because of this, and since 20 of the 29 patients were regarded as having outdoor occupations, it is suggested that a high environmental exposure to the fungus may be associated with an animal reservoir and with dry, dusty conditions. It is also possible that geographical and occupational factors rather than racial predisposition account for the high incidence of the disease in the Australian aborigine. However, individual resistance and susceptibility are probably also important factors, since the clinical disease appears to be positively correlated with certain other diseases, or with steroid therapy, which would impair the immune responses of the body. (3) Headache is the outstanding symptom of neurological cryptococcosis and fever or evidence of meningeal reaction, though often present, may be absent. An awareness of the possibility of neurological cryptococcosis in the differential diagnosis of various intracranial disorders should lead to identification of the encapsulated C. neoformans in the cerebrospinal fluid. Although in eight of 26 patients the lumbar cerebrospinal fluid was sterile on repeated examination, in five cases C. neoformans was found on direct examination of cerebrospinal fluid obtained by ventricular puncture. The remaining three died before further investigations could be performed. (4) Before the introduction of amphotericin B, neurological cryptococcosis was almost invariably fatal. At the present time, the infection can be eradicated in some 80% of patients. Intravenous administration of amphotericin B is generally adequate, but the intrathecal route should be used for cases in relapse or in critically ill patients. In addition to the toxic effects of the drug, the possibility of later deterioration in the patient's condition due to meningeal reaction-for example, occult hydrocephalus-merits

Topics: Adolescent; Adult; Aged; Amphotericin B; Australia; Central Nervous System Diseases; Child; Cryptococcosis; Female; Headache; Humans; Injections, Intravenous; Injections, Spinal; Male; Middle Aged; Occupations; Sex Factors

Topics: Amphotericin B; Blastomycosis; Central Nervous System Diseases; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Humans; Meningitis; Mycoses; Penicillins; Sputum; Sulfonamides

Topics: Agglutination; Amphotericin B; Animals; Antigens; Antigens, Fungal; Blood; Body Fluids; Central Nervous System Diseases; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Fluorescent Antibody Technique; Hodgkin Disease; Latex Fixation Tests; Lung Diseases; Microspheres; Rabbits; Research; Rubber

Topics: Amphotericin B; Central Nervous System Diseases; Cerebrospinal Fluid; Cryptococcosis; Humans; Laboratories; Medicine

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Humans

Topics: Amphotericin B; Antifungal Agents; Autopsy; Central Nervous System Diseases; Cryptococcosis; Cryptococcus neoformans; Humans

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Fungicides, Industrial

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Cryptococcosis; Female; Humans; Pregnancy; Pregnancy Complications