amphotericin-b and Cryptococcosis

Cryptococcosis is an opportunistic mycosis that mainly affects immunosuppressed patients. The treatment is a combination of three antifungal agents: amphotericin B, 5-flucytosine and fluconazole. However, these drugs have many disadvantages, such as high nephrotoxicity, marketing bans in some countries and fungal resistance. One of the solutions to find possible new drugs is pharmacological repositioning. This work presents repositioned drugs as an alternative for new antifungal therapies for cryptococcosis. All the studies here were performed

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Off-Label Use

Cryptococcosis is a fungal disease of public health relevance that affects numerous animal species and humans, causing respiratory and neurological impairment. Hence, we conducted a systematic review that included publications from 1975 to 2021 and covered 132 articles that addressed reports of cryptococcosis in domestic and wild animals, its main clinical manifestations, pathological findings, etiology, diagnosis, and therapeutic protocols. We found that the highest number of reports of cryptococcosis is in domestic species, especially cats. Among the wild and/or exotic animals, koalas and ferrets are the most affected, being important carriers of Cryptococcus spp. Pulmonary and neurological involvement is predominant in all species, although nonspecific clinical manifestations have been reported in various species, making clinical suspicion and diagnosis difficult. The countries with the most reports are Australia, the United States, Brazil, and Canada, with C. gattii VGI and VGII standing out. The therapies were based on azoles, amphotericin B, and 5-flucytosine, although there is no standard treatment protocol. Although, several diagnostic methods have been described, in a significant number of reports the diagnosis was made after a necropsy. Professionals are warned about diverse and nonspecific clinical manifestations in different animal species, which underlines the importance of cryptococcosis in the differential diagnosis in clinical practice. Furthermore, it is necessary to encourage the use of laboratory and molecular tools to improve the diagnosis of cryptococcosis. We also emphasize the urgent need for standardized therapeutic protocols to guide veterinary clinicians.. This review compiles studies on cryptococcosis in domestic and wild animals. Most reports occurred in cats and koalas. Pulmonary and neurological involvement was predominant in all affected species, and C. gattii VGI and VGII stood out in the etiology of the disease.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Ferrets; Flucytosine; Humans

Cryptococcosis is a neglected tropical disease and the main cause of fungal-related deaths in HIV-positive persons in Africa. It is an AIDS-defining illness that has almost surpassed tuberculosis (TB) in mortality despite wide coverage with antiretroviral therapy. What is known about the cryptococcosis burden in Africa is from estimations based on data from a few studies on the infection burden and associated complications. Consequently, the projected implications of cryptococcosis in Africa have been based on these estimations. This systematic review is aimed at providing unique and up-to-date data on the burden of cryptococcosis in Africa using published hospital-based research data on cryptococcosis in HIV infected and uninfected persons. The review also focused on providing temporal data on the availability of diagnostic and therapeutic options for cryptococcosis in Africa. From our results, about 40 948 cases of cryptococcosis were reported in Africa from 1969 to 2021, and the highest prevalence of cryptococcosis was from southern Africa. The most isolated species was Cryptococcus neoformans 42.4% (17 710/41 801) and only 1.3% (549/41 801) isolates were C. gattii. C. neoformans (serotype A) VN I 64.5% (918/1522) was the most prevalent serotype in Africa, while C. gattii (serotype C) VG IV was thought to pose a huge danger. However, C. neoformans (serotype A) VN I continued to be the major threat in Africa. Due to the limited availability of molecular typing methods and the widespread use of culture, direct microscopy, and serological techniques for diagnosis, 23 542 isolates were uncharacterised. Amphotericin B and flucytosine combination therapy is highly recommended for treatment of cryptococcal meningitis. However, these drugs are expensive and remain largely unavailable in most African countries. Amphotericin B requires laboratory facilities to monitor for toxicity. Although fluconazole monotherapy is the readily available treatment option for cryptococcosis, drug resistance, and high mortality have been recorded in majority of cases in Africa. The lack of awareness and paucity of published data on cryptococcosis are likely to have contributed to the underestimation of cases in Africa and led to underprioritisation of this important disease.. Cryptococcosis is a neglected tropical disease that manifests greatly in immunocompromised persons especially those with HIV infection. Our data show that managing cryptococcosis will require an integrated multidisciplinary approach that should include the utilisation of cryptococcal antigen (CrAg) testing, which is highly sensitive and cost-effective for diagnosing this disease.

Topics: Africa; Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans

There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Flucytosine; Humans

Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; HIV Infections; Humans; Meningitis, Cryptococcal

Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.. A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.. This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cellulitis; Coinfection; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Male; Mycobacterium haemophilum; Mycobacterium Infections; Nitriles; Opportunistic Infections; Primary Myelofibrosis; Pyrazoles; Pyrimidines

Cryptococcal meningoencephalitis was first described over a century ago. This fungal infection is preventable and treatable yet continues to be associated with excessive morbidity and mortality. The largest burden of disease resides in people living with HIV in low-income and middle-income countries. In this group, mortality with the best antifungal induction regimen (7 days of amphotericin B deoxycholate [1·0 mg/kg per day] and flucytosine [100·0 mg/kg per day]) in a clinical trial setting was 24% at 10 weeks. The world is now at an inflection point in terms of recognition, research, and action to address the burden of morbidity and mortality from cryptococcal meningoencephalitis. However, the scope of interventional programmes needs to increase, with particular attention to implementation science that is specific to individual countries. This Review summarises causes of excessive mortality, interventions with proven survival benefit, and gaps in knowledge and practice that contribute to the ongoing high death toll from cryptococcal meningoencephalitis. TRANSLATIONS: For the Vietnamese and Chichewa translations of the abstract see Supplementary Materials section.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Databases, Factual; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Meningoencephalitis

Cryptococcosis has become an important infection in both immunocompromised and immunocompetent hosts. Although

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Immunocompromised Host; Lung Diseases, Fungal; Radiography

Colonic cryptococcal infection is unusual in people living with HIV (PLWH) and even more so without concomitant neurological compromise. Published case reports describe diarrhea and other intestinal manifestations that are often confused with systemic tuberculosis infection. We describe an Peruvian woman living with HIV on antiretroviral therapy who presented hypotensive with a 6-month history of fever and epigastric pain, in addition to episodes of sporadic diarrhea. Due to the suspicion of systemic tuberculosis, antituberculosis treatment was started. Days later, without clinical improvement, colonoscopy revealed ulcers in the transverse colon. Histopathological examination of biopsied tissue was compatible with

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; HIV Infections; Humans; Hypotension; Immunosuppression Therapy; Pain; Treatment Outcome

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

Cryptococcus albidus, synonymous with Naganishia albida, rarely causes opportunistic infection in immunocompromised individuals. Its clinical features, particularly in children, are not well defined. Here, we report a case of C albidus fungemia in an immunosuppressed child; we also present results of a systematic review, for which we searched PubMed, Embase, and Web of Science using the keywords "cryptococcus" and "albidus." Our goal was to describe the spectrum of disease, diagnostic approaches, therapies, and outcomes. We identified 20 cases of invasive infection, only 2 of which involved children, and 7 cases of noninvasive infection. The reports originated in the Americas, Europe, and Asia. Of those with invasive infection, 16 (80%) patients had an underlying chronic disorder or had received immunosuppressive therapy, 8 (40%) had fungemia, and 6 (30%) had a central nervous system infection. The attributable case fatality rate was 40%. C albidus is an opportunistic yeast that can rarely cause life-threatening fungemia and central nervous system infection in individuals of any age, especially those who are immunocompromised.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Cryptococcus; Female; Fluconazole; Humans; Immunocompromised Host; Infant, Newborn; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Takayasu Arteritis; Transplantation, Autologous

We report two cases of cryptococcosis, associated with anti-granulocyte-macrophage colony-stimulating factor antibodies. We review this recently identified acquired form of autoimmune immune deficiency and discuss the potential applications of granulocyte-macrophage colony-stimulating factor antibody testing by enzyme-linked immunosorbent assay.

Topics: Adult; Amphotericin B; Antifungal Agents; Autoantibodies; Brain; Cryptococcosis; Cryptococcus neoformans; Enzyme-Linked Immunosorbent Assay; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lung Diseases, Fungal; Magnetic Resonance Imaging; Male; Meningitis, Cryptococcal; Middle Aged; Tomography, X-Ray Computed

Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis.. We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient's treatment, but unfortunately, he died three days later. Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy.. Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Antifungal Agents; Antigens, Fungal; China; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Male; Meningitis; Middle Aged; Opportunistic Infections; Treatment Outcome

To describe a case of bilateral endogenous cryptococcal endophthalmitis in an immunocompetent host and to review adjunctive ophthalmic imaging patterns and treatment.. A retrospective case report.. A 45-year-old female patient with two distinct presentations of endogenous cryptococcal endophthalmitis in each eye presented initially with progressive blurred vision in the left eye, beginning more than 10 years after a craniotomy with ventriculoperitoneal shunt. Complete ophthalmic imaging was conducted and compared with data from previous literature. Administration of amphotericin-B had poorly responded; however, consolidation of fluconazole resulted in disease stabilization.. Bilateral intraocular cryptococcal infection can present with two distinct patterns of posterior segment findings. A review of ophthalmic imaging patterns found consistency in some characteristics of A-scan ultrasonogram and fundus fluorescein angiogram. Besides conventional treatment, voriconazole is likely to play an important role in the management of cryptococcal endophthalmitis.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Endophthalmitis; Eye Infections, Fungal; Female; Fluorescein Angiography; Fundus Oculi; Humans; Immunocompromised Host; Injections, Intravenous; Intravitreal Injections; Middle Aged; Multimodal Imaging; Ultrasonography

We report a case of

Topics: Adenine; Aged; Amphotericin B; Antibodies, Monoclonal, Murine-Derived; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cryptococcosis; Cryptococcus neoformans; Cyclophosphamide; Doxorubicin; Empyema, Pleural; Fluconazole; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Piperidines; Prednisone; Pyrazoles; Pyrimidines; Rituximab; Vincristine

Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations. Disseminated C. neoformans infection in immunocompetent population is rare and usually involves lung and central nerve system. Cryptococcus from biologic samples can easily grow on routine fungal and bacterial culture media. Besides, cryptococcal latex agglutination test has been established as a reliable diagnostic tool with overall sensitivities of 93-100%.. We report a rare disseminated cryptococcosis case which presented with chronic recurrent multiple abscess in an immunocompetent male involving skin, lung, spine and iliac fossa without evidence of central nerve system involving. The results of serum cryptococcal latex agglutination tests and standard microbial cultures were negative. The patient underwent empirical anti-bacterial and anti-tuberculosis therapy which turned out to be effectless. Finally, bedside inoculation of the pus was carried out and revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction. After the administration of anti-fungal drugs including liposomal amphotericin B, the patient recovered from fever and paraplegia.. This case reveals an uncommon pattern of disseminated C. neoformans infection in immunocompetent population presented with chronic multiple abscess and without central nerve system involving. Negative routine microbial cultures may not necessarily rule out cryptococcosis, especially in early stage. Besides, cryptococcal latex agglutination test does have a chance of false negative, which might be related with "capsule-deficiency". Moreover, this phenomenon could be related with low-grade virulence and relative long illness duration.

Topics: Abscess; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Immunocompromised Host; Latex Fixation Tests; Male; Spine

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Hematologic Neoplasms; Humans; Lymphoma; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections

Cryptococcus neoformans is a fungal pathogen associated with advanced HIV disease and other disorders associated with immune dysfunction. The pulmonary and the central nervous system are the most common manifestations of the disease. Localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. Herein, we present five cases of Cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. We also identified 84 additional cases of isolated cryptococcal osteomyelitis in the literature. Using these data, we have made some general recommendations regarding an approach to treatment of this uncommon clinical entity.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Female; Hepatitis C; HIV Infections; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Sarcoidosis; Tomography, X-Ray Computed; Young Adult

Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, primarily caused by Cryptococcus neoformans and Cryptococcus gattii. In China, C. neoformans var. grubii (especially molecular type VNI) is the most common variety in the environment and responsible for the majority of cryptococcal infections. C. gattii infections are quite rare in China and the primary molecular type is VGI, which is closely related to C. gattii isolates in Australia. Interestingly, the majority of cryptococcosis in China were reported in the HIV-uninfected patients (especially immunocompetent hosts). This unique phenomenon may be attributed to multiple polymorphisms in the genes encoding mannose-binding lectin (MBL) and Fc-gamma receptor 2B (FCGR2B) in the Han population, the major ethnic group in China. Compared to immunocompromised patients, immunocompetent patients with cryptococcal meningitis often presented with more intense inflammatory responses and more severe neurological complications, but less fungal burdens and disseminated infection. The overall prognosis, which is independently associated with amphotericin B-based initial therapy, is similar between immunocompetent and immunocompromised patients. In addition, intrathecal administration of amphotericin B has been proved to be an effective adjunctive treatment for cryptococcosis in China.

Topics: Amphotericin B; Antifungal Agents; China; Cryptococcosis; Cryptococcus neoformans; Genotype; HIV Infections; Humans; Injections, Spinal; Molecular Epidemiology; Mycological Typing Techniques; Survival Analysis; Treatment Outcome

Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline.

Topics: Acitretin; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Azoles; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Doxycycline; Granuloma Inguinale; Histoplasmosis; Humans; Keratolytic Agents; Lymphogranuloma Venereum; Mycoses; Pyoderma; Sexually Transmitted Diseases; Sporotrichosis

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Coccidioides; Coccidioidomycosis; Colon; Cryptococcosis; Cryptococcus; Duodenal Ulcer; Endemic Diseases; Female; Histoplasma; Histoplasmosis; Humans; Itraconazole; Job Syndrome; Male; Middle Aged; Mutation; STAT3 Transcription Factor; Treatment Outcome; Triazoles; United States

Cryptococcus neoformans infection usually presents as chronic meningitis and is increasingly being recognized in immunocompromised patients. Presentation with pleural effusion is rare in cryptococcal disease; in fact, only 4 cases of pleural effusion as the initial clinical presentation in cryptococcosis have been reported in English-language literature to date. We report the first case of pleural effusion as the initial clinical presentation in a renal transplant recipient who was initially misdiagnosed with tuberculous pleuritis but who then developed fungaemia and disseminated cryptococcosis. The examination of this rare manifestation and the accompanying literature review will contribute to increased recognition of the disease and a reduction in misdiagnoses.. We describe a 63-year-old male renal transplant recipient on an immunosuppressive regimen who was admitted for left pleural effusion and fever. Cytological examinations and pleural fluid culture were nonspecific and negative. Thoracoscopy only found chronic, nonspecific inflammation with fibrosis in the pleura. After empirical anti-tuberculous therapy, the patient developed an elevated temperature, a severe headache and vomiting and fainted in the ward. Cryptococci were specifically found in the cerebrospinal fluid following lumbar puncture. Blood cultures were twice positive for C. neoformans one week later. He was transferred to the respiratory intensive care unit (RICU) immediately and was placed on non-invasive ventilation for respiratory failure for 2 days. He developed meningoencephalitis and fungaemia with C. neoformans during hospitalization. He was given amphotericin B liposome combined with 5-flucytosine and voriconazole for first 11 days, then amphotericin B liposome combined with 5-flucytosine sustained to 8 weeks, after that changed to fluconazole for maintenance. His condition improved after antifungal treatment, non-invasive ventilation and other support. Further pathological consultation and periodic acid-Schiff staining revealed Cryptococcus organisms in pleural sections, providing reliable evidence for cryptococcal pleuritis.. Pleural effusion is an unusual manifestation of cryptococcosis. Cryptococcal infection must be considered in the case of patients on immunosuppressives, especially solid-organ transplant recipients, who present with pleural effusion, even if pleural fluid culture is negative. Close communication between the pathologist and the clinician, multiple special biopsy section stains and careful review are important and may contribute to decreasing misdiagnosis.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Flucytosine; Fungemia; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pleural Effusion; Voriconazole

Cryptococcosis occurring within 30 days after transplant is unusual. We present a case of cryptococcosis diagnosed within 2 weeks of liver transplant and cryptococcal infection transmitted by liver transplant is considered as the cause. A 63-year-old woman with hepatitis C virus-related cirrhosis and hepatocellular carcinoma had an orthotopic liver transplant from a 45-year-old donor. The immediate postoperative course was smooth, although she was confused with a fever, tachycardia, respiratory failure of 1 week's duration after the orthotopic liver transplant. A liver biopsy was performed for hyperbilirubinemia 2 weeks after the orthotopic liver transplant that showed a Cryptococcus-like yeast. Her blood culture was reexamined, and it was confirmed as Cryptococcus neoformans that had been misinterpreted as candida initially. At the time of the re-examination, her sputum was clear. We checked her preoperative blood sample, retrospectively, for serum cryptococcal antigen with negative result. She was on liposomal amphotericin treatment for 1 month when her blood culture became negative. She was discharged home, with good liver function and a low antigen titer for cryptococcal infection. Cryptococcal disease usually develops at a mean of 5.6 months after transplant. However an early occurrence is rare. Apart from that, its variable clinical presentations make early detection difficult. It might be an early reactivation or a donor-derived infection. The latter usually occurs in unusual sites (eg, the transplanted organ as the sole site of involvement). Our case presented as cryptococcoma and liver involvement was diagnosed by an unintentional liver biopsy.

Topics: Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Hyperbilirubinemia; Liver; Liver Transplantation; Middle Aged; Time Factors; Tissue Donors; Treatment Outcome

Although therapeutic first-line approaches have been established in severely immunosuppressed patients with a high risk of invasive fungal infections, treatment modalities for cases with unsatisfactory outcome have not been well defined, especially for the pediatric age gap. Therapy with coadministration of two or three antifungals has been applied by clinicians in difficult-to-treat infections, which still have no support from randomized, controlled clinical trials. The most prevailing reason for a combination regimen is to broaden the antimycotic spectrum, which may even result in antagonistic interaction. The experience and recommendations of combinational antifungal therapy for cryptococcal infections, systemic candidiasis, invasive aspergillosis and other rare mold infections have been presented in this review, giving some information on mechanism of action and principles in combined use of mycotic anti-infectives. Most experience of combination therapy approaches are in adult patients; but in fact, there is no conclusive data documenting definite benefits of this approach, either in adults or children.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Caspofungin; Child; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Echinocandins; Humans; Lipopeptides; Pyrimidines; Triazoles; Voriconazole

Invasive fungal infections (IFIs) are important causes of morbidity and mortality in immunocompromised children. The increased incidence and high mortality rates associated with IFIs has led to development of novel antifungal agents to expand the breadth and effectiveness of treatment options available to clinicians. Since its initial approval in 1958, conventional amphotericin B deoxycholate had been considered the standard in treatment for IFIs. However, because of the dose-limiting toxicity of conventional amphotericin B deoxycholate, lipid formulations of amphotericin have been developed to potentially improve outcomes and mitigate the adverse effects associated with antifungal therapy. While less frequently employed today as prophylaxis (given the expanded availability of safer alternatives), amphotericin B is still considered a treatment option in select cases of severe or life-threatening IFIs. This article reviews the clinical use of amphotericin B for the prevention and treatment of IFIs.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis, Invasive; Chemistry, Pharmaceutical; Child; Cryptococcosis; Humans; Lipids; Zygomycosis

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

Cryptococcus neoformans usually involves the central nervous system and the respiratory tract. We report a case of disseminated cryptococcosis with a liver abscess and meningoencephalitis in a patient with myelodysplastic syndrome. Computed tomography of the abdomen showed a 3-cm low-attenuated lesion in the left lobe of liver. Cultures from specimens of blood, the liver abscess, and the cerebrospinal fluid all yielded C. neoformans. The cryptococcal antigen titers for the serum and cerebral fluid were both 1:32. The patient was successfully treated with 1,335 mg of amphotericin-B followed by fluconazole. Most cryptococcal liver infections present as hepatitis, cholangitis, or microabscesses.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Liver Abscess; Tomography, X-Ray Computed; Ultrasonography

Expanding access to antiretroviral treatment has dramatically improved the long-term prognosis of patients with HIV-associated cryptococcal disease who survive the acute infection. However, the incidence and acute mortality of HIV-associated cryptococcal meningitis remain high. In this context, this review summarizes urgently needed recent work aimed at improving the acute management of cryptococcal infection in immunocompromised hosts.. Studies have started to optimize antifungal regimens and address the complications of raised cerebrospinal fluid pressure and cryptococcal immune reconstitution syndrome. Amphotericin B at 1 mg/kg per day has been shown to be more rapidly fungicidal than the standard dose of 0.7 mg/kg per day, and new data support the importance of combination therapy with flucytosine. Amphotericin B and fluconazole at 800 mg is an alternative combination that appears superior to amphotericin B alone. At a dosage of 400 mg per day, fluconazole alone is much less rapidly fungicidal than amphotericin B and is associated with the development of secondary resistance.. Recent findings support the use of rapidly fungicidal initial antifungal therapy with amphotericin B-based combination treatment. Where amphotericin B treatment is not yet feasible, studies are needed to optimize oral regimens. Based on accumulating data on rate of clearance of infection, the most promising new regimens in terms of fungicidal activity and safety could be selected for clinical endpoint trials.

Topics: Amphotericin B; Antifungal Agents; Case Management; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Immunocompromised Host

Cryptococcosis is a common fungal infection that caused by Cryptococcus neoformans in immunocompetent individuals as well as in immunosuppressive patients with such as the HIV infection. Measurements of the values of glucuronoxylomannan structuring capsule of C. neoformans in serum or cerebrospinal fluid are quite useful to diagnosis of pulmonary cryptococcosis and cryptococcal meningitis as major two forms of cryptococcosis. Azole anti-fungal agents including fulconazole, itraconazole for pulmonary cryptococcosis, and amphotericin B plus flucytosine for cryptococcal meningitis are recommended as first line therapy in Japanese guideline for the diagnosis and treatment of deep seated mycosis revised in 2007. The clinical appearance, diagnostic methods, treatment and prognosis of pulmonary cryptococcosis and cryptococcal meningitis are described based on the Japanese guideline in this manuscript.

Topics: Amphotericin B; Antifungal Agents; Azoles; Biomarkers; Cryptococcosis; Cryptococcus neoformans; Diabetes Complications; Drug Therapy, Combination; Humans; Immunocompromised Host; Lung Diseases, Fungal; Meningitis, Cryptococcal; Polysaccharides; Practice Guidelines as Topic; Prognosis; Tomography, X-Ray Computed

Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age > or =45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.

Topics: Amphotericin B; Cryptococcosis; Drug Resistance, Fungal; Humans; Risk Factors

Although cryptococcal infections due to Cryptococcus neoformans are frequently reported in the immunosuppressed patients, infections related to other Cryptococcus spp. are rarely reported. We are reporting a case of pulmonary infection and ARDS due to C. albidus in a patient receiving immunosuppressive therapy because of Still's disease. The diagnosis was made by tissue biopsy and culture. The patient responded to treatment with amphotericin B lipid complex 400 mg/day. The case is significant in that it reminds of yeasts as a cause of community acquired infection in the immunosuppressed patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus; Drug Combinations; Humans; Lung; Male; Phosphatidylcholines; Phosphatidylglycerols; Pneumonia; Respiratory Distress Syndrome

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following transplantation are relatively common due to the transplant recipients overall immunosuppressed status. The incidence of invasive mycoses following solid organ transplant ranges from 5 to 42% depending on the organ transplanted. These mycoses are associated with high overall mortality rates. Candida and Aspergillus spp. produce most of these infections. This article will review the risk factors, clinical presentation and treatment of invasive fungal infections in solid organ transplant patients, and evaluate the role of prophylactic therapy in this group of patients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Clinical Trials as Topic; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Echinocandins; Fluconazole; Humans; Incidence; Lipopeptides; Organ Transplantation; Peptides, Cyclic; Postoperative Complications; Premedication

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcosis; Humans; Male; Oral Ulcer; Palate; Scalp; Skin Diseases, Infectious

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Fluconazole; Humans; Immunity, Cellular; Immunocompromised Host; Melanins; Polysaccharides; Prognosis; Virulence Factors

The increase in the incidence of fungal infections and the emergence of resistance call for the development of techniques for measuring in vitro antifungal susceptibility that are useful for predicting clinical outcome in patients suffering from these infections. In the past, the lack of standardized testing techniques led to poor intra- and interlaboratory reproducibility. Recently, the National Committee for Clinical Laboratory Standards (NCCLS) has developed a reference method for antifungal susceptibility testing, document M27A. This document is a necessary and important step towards the standardization of antifungal susceptibility testing, which has important implications in the analysis of clinical and microbiological data. This article provides a comprehensive review of studies correlating in vitro antifungal susceptibility testing and clinical outcome. In general, it is possible to predict the therapeutic outcome, especially in HIV infected patients with oropharyngeal candidiasis treated with fluconazole. However, in other more heterogeneous groups of patients it is more difficult to correlate the in vitro and in vivo data.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cryptococcosis; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests

Cryptococcus neoformans, an encapsulated yeast is responsible for life-threatening infection in patients with cellular immune defect especially those with AIDS. The most frequent presentation of cryptococcosis is a disseminated meningoencephalitis without acute onset. The diagnosis is based on direct examination with India ink staining, detection of soluble capsular polysaccharide in body fluids, culture of the micro-organism or histology. Looking for other localisations and for factors of poor prognosis is mandatory before selecting the right treatment regimen. In case of meningitis, one should prefer a combination of amphotericin B and 5 fluorocytosin, followed by a triazole, usually fluconazole until sterilisation of all infected sites is achieved or even for life-time maintenance therapy in case of sustained immune defect.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Child; Cryptococcosis; Female; Flucytosine; Humans; Male; Meningitis, Cryptococcal; Mycology; Prognosis; Risk Factors; Time Factors

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV; HIV Infections; Humans; Itraconazole; Lung Diseases, Fungal; Meningitis, Cryptococcal; Randomized Controlled Trials as Topic

Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fluconazole; Flucytosine; Fungemia; Histoplasmosis; Humans; Immunocompromised Host; Mycoses; Zygomycosis

A case of cryptococcal rib osteomyelitis in a pediatric patient is described. Isolated cryptococcal osteomyelitis in pediatric patients is a rare entity, and only 10 cases have been reported in the literature. The radiological findings are reviewed to include chest films, nuclear bone scan, and computed tomographic imaging scan. Because of its rarity, the management of isolated cryptococcal osteomyelitis is controversial. Although antifungal antibiotics and surgery are the two therapeutic options, the treatment of cryptococcal osteomyelitis has not been standardized yet. This patient was treated successfully with limited resection of the involved rib and antifungal chemotherapy. This article describes the second case in the literature of cryptococcal rib osteomyelitis in a pediatric patient, reviews the literature of similar cases, and evaluates the current role of surgery in its treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Cryptococcosis; Cryptococcus neoformans; Disease-Free Survival; Female; Humans; Osteomyelitis; Ribs

Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Hodgkin Disease; Humans; Male; Middle Aged; Opportunistic Infections

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Azoles; Clinical Trials as Topic; Cryptococcosis; Drug Interactions; Flucytosine; Humans

Topics: Amphotericin B; Animals; Antifungal Agents; Columbidae; Cryptococcosis; Humans; Immunocompromised Host; Lung Diseases, Fungal; Pneumonia; Zoonoses

Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Fluconazole; Humans; Middle Aged; Mucormycosis; Opportunistic Infections

The availability of standard guidelines (NCCLS M27 document) for antifungal susceptibility testing has facilitated the establishment of tentative interpretive breakpoints for fluconazole and itraconazole by the NCCLS. Based on correlations of MIC values with the outcomes of patients with mostly Candida infections, fluconazole MICs of > or = 64 and itraconazole MICs of > or = 1.0 microgram/mL are considered resistant. Fluconazole MICs of 16 to 32 micrograms/mL and itraconazole MICs of 0.2 to 0.5 microgram/mL were categorized as "susceptible dependent upon dose" (S-DD), that is, clinical response may be obtained with increased doses. Susceptible breakpoints for fluconazole and itraconazole correspond to < or = 8 and < or = 0.12 microgram/mL, respectively. For flucytosine, resistant and susceptible breakpoints for Candida were set at > or = 32 micrograms/mL and 4 micrograms/mL, respectively, based on historical data and the drug's pharmacokinetics for Candida. Although no breakpoints have been established for amphotericin B, clinical failure has been associated with MICs > 1.0 microgram/mL.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cryptococcosis; Drug Resistance, Microbial; Fluconazole; Flucytosine; Humans; Itraconazole; Mycoses

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Azoles; Cryptococcosis; Female; Histoplasmosis; HIV Infections; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mouth Diseases; Mucormycosis; Mycoses; Sinusitis

Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.

Topics: Amphotericin B; Animals; Aspergillosis; Blastomycosis; Candidiasis; Cell Death; Cell Membrane; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Detergents; Drug Carriers; Drug Delivery Systems; Drug Industry; Histoplasmosis; Immunity, Active; Leishmania; Leishmaniasis, Visceral; Lipoproteins; Mice; Molecular Structure; Phospholipids; Rabbits

Cryptococcosis is a major cause of illness and death among persons infected with human immunodeficiency virus (HIV). Its management must include both initial and maintenance treatment. Although most authorities favor an initial period of therapy with amphotericin B for acute cryptococcosis, the triazoles play a role in both the management of acute disease and subsequent maintenance therapy. AIDS surveillance data collected by the Centers for Disease Control and Prevention document the occurrence of cryptococcosis in more than 17,000 (6.2%) of adults with AIDS in the United States, although this figure is known to be an underestimate. The risk of cryptococcosis among HIV-infected persons is highest at CD4+ lymphocyte counts of < 100/microL. Although cryptococcosis is especially frequent among AIDS patients who are black, male, or injection drug users, the explanations for these patterns remain unclear. Whether geographic differences in rates of cryptococcosis result from variations in the environmental distribution of Cryptococcus neoformans as well as in the distribution of HIV infection is also unclear. Although exposure to pigeon feces is the best known of the putative exposure-related risk factors, proof is lacking that avian excreta are the primary environmental source of the organism in most cases of cryptococcosis. Prophylaxis with triazoles can prevent cryptococcosis and may be considered for adults and adolescents with CD4+ counts of < 50/microL. However, it is uncertain whether prophylaxis will affect survival, be cost-effective, or have an adverse impact on the susceptibility of a variety of fungi to antifungal drugs. Vaccines and monoclonal antibodies designed to prevent or modify cryptococcosis in HIV-infected persons are in the experimental stage.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; HIV Infections; Humans; Incidence; Male; Risk Factors; United States

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antifungal Agents; Clinical Trials as Topic; Cryptococcosis; Fluconazole; Flucytosine; Humans; Immunotherapy; Itraconazole; Meningitis, Cryptococcal; Mice; Multicenter Studies as Topic; Vaccination

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Candidiasis, Chronic Mucocutaneous; Clinical Trials as Topic; Cryptococcosis; Double-Blind Method; Fluconazole; Humans; Itraconazole; Ketoconazole; Mucormycosis; Mycoses; Neutropenia; Nystatin; Primary Prevention; Recurrence; Retrospective Studies

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Candidiasis, Oral; Candidiasis, Vulvovaginal; Child; Clinical Trials as Topic; Cryptococcosis; Drug Resistance, Microbial; Esophageal Diseases; Female; Fluconazole; Fungi; Humans; Ketoconazole; Male; Retrospective Studies

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Fluconazole; Flucytosine; Hematologic Diseases; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney; Mycoses; Thrombophlebitis

To assess the role of azole therapy in the treatment and prophylaxis of cryptococcosis in HIV-seropositive individuals.. Retrospective case review.. A dedicated HIV unit in London, UK.. Fifty individuals with a positive cryptococcal antigen or culture from any site between 1 January 1985 and 31 December 1992.. Thirty-eight patients initially presented with meningitis and 12 with alternative disease, five of whom subsequently developed meningeal disease. The 12 patients who presented without meningitis received chronic suppressive therapy after the diagnosis of cryptococcal disease. Two patients receiving itraconazole developed meningitis as did three out of four treated with 200 mg fluconazole daily, but none of the six receiving 400 mg fluconazole daily. Treatment of cryptococcal meningitis was successful in 17 of the 19 patients given fluconazole but only three of the six receiving itraconazole. Following successful treatment of meningitis five out of seven patients given itraconazole and five out of seven given 200 mg fluconazole daily relapsed compared with three out of 25 receiving 400 mg fluconazole daily.. Fluconazole is an effective treatment for cryptococcal meningitis. For prophylaxis following meningitis, a dose of 400 mg fluconazole is the preferred treatment; lower doses are associated with a higher relapse rate.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Fluconazole; Fungemia; Humans; Itraconazole; London; Meningitis, Cryptococcal; Recurrence; Retrospective Studies; Survival Analysis

In patients with AIDS with cryptococcosis, prompt diagnosis is essential. Poor results with conventional therapy (amphotericin-5FC) have led to exploration of the azoles. Both fluconazole and itraconazole have given good short-term results with less toxicity. However, cure is achieved far less often than in other compromised hosts. Fluconazole is also useful to prevent relapse after successful initial amphotericin therapy, particularly from genitourinary foci. In both histoplasmosis and aspergillosis, itraconazole has produced impressive therapeutic results, and in histoplasmosis, secondary prophylaxis as well. In coccidioidomycosis results thus far have not been better than conventional amphotericin therapy, especially in initial treatment.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Coccidioidomycosis; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Histoplasmosis; Humans; Itraconazole; Meningitis, Cryptococcal

The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol. Early studies of its efficacy in an open design showed that remissions could be induced in candidosis and aspergillosis and that doses of up to 5 mg/kg could be used. Adverse events were infrequent, with the main abnormality seen being hypokalaemia in about 18% of patients. Subsequent developments have extended this work. AmBisome has been used in two open studies of patients with invasive aspergillosis; in one of these remission was achieved in 77% of 17 patients with confirmed infection who had failed to respond to conventional amphotericin B. In AIDS patients with cryptococcosis AmBisome given for 6 weeks at 3 mg/kg daily produced mycological remission of meningitis in 67%. Other infections treated with the drug include zygomycete (mucormycosis) and Fusarium infections. AmBisome has also been used as preventative therapy in bone marrow transplant recipients and was found to reduce fungal colonisation rates. There were fewer systemic fungal infections in the treated versus placebo groups although this did not achieve statistical significance. Lack of renal and liver toxicity or anaemia has been confirmed in subsequent studies. In addition febrile reactions to the AmBisome are rare. The drug has also been used effectively in children, including infants, with systemic fungal infections. In visceral leishmaniasis patients, including HIV positive individuals, remissions have been obtained using drug regimens of 1-2 mg/kg of 2.1 days and 3 mg/kg for 10 days.

Topics: Amphotericin B; Aspergillosis; Clinical Trials as Topic; Cost-Benefit Analysis; Cryptococcosis; Drug Carriers; Humans; Liposomes; Mycoses

Cryptococcosis is a common opportunistic fungal disease in immunocompromised patients and also may occur in normal hosts. Cryptococcal disease most frequently involves the lungs and central nervous system. Management remains controversial, especially in patients with life-threatening disease and those with underlying T-cell dysfunction due to AIDS, neoplasia, or corticosteroid therapy. While amphotericin B, usually in combination with flucytosine, generally is recommended as primary therapy for patients with severe forms of disease, especially cryptococcal meningitis, alternative treatment regimens have been developed or are under investigation. These include the use of an oral triazole alone (fluconazole or itraconazole), an all-oral combination of fluconazole and flucytosine, and a novel induction-consolidation regimen using several drugs. Patients with AIDS are at high risk of relapse; consequently, chronic maintenance therapy is indicated. For patients with cryptococcal meningitis who have hydrocephalus or other central nervous system complications, aggressive adjunctive measures such as ventricular shunting must be employed.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Lung Diseases, Fungal; Meningitis; Triazoles

A patient developed cryptococcal peritonitis with systemic dissemination during continuous ambulatory peritoneal dialysis (CAPD). This case prompted a search of the literature for cases of cryptococcal peritonitis; 19 previously reported cases were identified. On the basis of their clinical characteristics, these cases were divided into two groups. Group 1 included 10 cases developing during CAPD. Treatment consisted of removal of the peritoneal dialysis catheter and administration of a short course of amphotericin B. Eight of the 10 cases had a benign course, and nine patients survived. Group 2 comprised 10 cases developing in patients with severe underlying illnesses, such as chronic liver disease, AIDS, systemic lupus erythematosus, and leukemia. Disseminated cryptococcosis was documented in eight of the nine patients in this group for whom relevant information was available. Seven patients died, some despite antifungal therapy. Cryptococcal disease may have protean manifestations and an insidious course. Accordingly, the diagnosis of cryptococcal peritonitis may well be delayed. An awareness of this entity may lead to earlier diagnosis and treatment and possibly to improved outcome.

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Infusions, Intravenous; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

Cryptococcal infection is the most common fungal infection of the central nervous system. More than 50% of the cases of cryptococcal infection are superimposed on an immunosuppressive or other general debilitating condition. Cerebral cryptococcosis usually presents as meningitis or meningoencephalitis, although cerebral granuloma has also been reported. Hydrocephalus is the most common neurosurgical complication of cerebral cryptococcosis. The majority of patients require only medical treatment with antifungal drugs. However, when complications ensue, surgical intervention is mandatory. We suggest that chronic meningitis be ruled out in all patients prior to the placement of shunts. In the two cases reported here treatment of cryptococcal meningitis was a combination of amphotericin B and flucytosine for six weeks. Fluconazole is a new alternative and at least as effective as amphotericin B.

Topics: Adolescent; Adult; Agammaglobulinemia; Amphotericin B; Brain Abscess; Brain Diseases; Cryptococcosis; Female; Flucytosine; HIV Seronegativity; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Opportunistic Infections

Topics: Amphotericin B; Animals; Cross Infection; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Humans; Opportunistic Infections

C albidus and mucormycosis were cultured simultaneously from the pleural space of a patient with end-stage renal disease receiving long-term hemodialysis. There have been only nine previous reports of infection with C albidus, with only one involving the lung. This organism has never before been isolated from the pleural space, and none of the previously reported cases included a coinfection with mucormycosis. We have reviewed and compared all known cases of infection with C albidus.

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus; Empyema, Pleural; Humans; Kidney Failure, Chronic; Male; Middle Aged; Mucormycosis; Renal Dialysis

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: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Fluconazole; Flucytosine; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal

Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy. Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy. Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings. The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Drug Resistance, Microbial; Humans; Infusions, Intravenous; Mycoses

Cryptococcus neoformans is an opportunistic fungus with a predilection for infecting the meninges. Ocular sequelae of cryptococcal infections of the CNS usually include cranial nerve palsies or papilledema secondary to increased intracranial pressure. Intraocular cryptococcosis occurs less frequently, and over the last 23 years, only 27 cases have been reported, including the case presented here. Intraocular infection was most often manifested by chorioretinal lesions and vitritis. Underlying diseases were detected in only 11 (41%) of the 27 patients. Of note, ocular lesions preceded symptomatic meningitis in six (27%) of 22 patients with CNS involvement. For seven patients, the diagnosis was made by histologic examination of specimens of aqueous or vitreous humor; for another eight patients, the diagnosis was made after enucleation or at autopsy. Ocular involvement frequently led to severe visual loss; return of vision to normal was unusual. Early recognition and treatment may improve outcome for these patients.

Topics: Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Endophthalmitis; Eye Infections, Fungal; Female; Flucytosine; Humans; Treatment Outcome

Cryptococcosis is currently the most common life threatening mycoses found in patients with the acquired immunodeficiency syndrome (AIDS). Extrapulmonary involvement is most frequently seen, especially in the central nervous system and skin. Clinical findings are non-specific, even in patients with meningitis. Threshold for diagnosis of this infection should be low, with serum cryptococcal antigens, blood, urine and sputum cultures for Cryptococcus neoformans performed in febrile AIDS patients. Lumbar puncture should also be performed if unexplained headaches are included in a patient's complaints. There is currently no consensus for the most appropriate treatment strategy and the role of oral azoles versus amphotericin B or amphotericin B with flucytosine remains a serious question in need of further controlled studies. Patients eligible for multicentered trials should be encouraged to participate. Therapy for others should be individualized. This review will address some of these issues.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Fluconazole; Flucytosine; Humans

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Dermatomycoses; Diagnosis, Differential; Fluconazole; Humans; Injections, Spinal; Meningitis; Molluscum Contagiosum; Opportunistic Infections; Prognosis

Cryptococcosis is the most common life-threatening mycosis with AIDS. The combination therapy based on amphotericin B and flucytosine is furthermore the therapy of first choice, even after introduction of fluconazole. With a therapy maintained over a period of 6 weeks the combination is nearly always successful; a shorter treatment period leads to minor treatment success. Since no elimination of the pathogen is possible in cryptococcosis with AIDS a permanent relapse prevention is necessary. In this prevention strategy fluconazole is highly effective and at present the drug of first choice; it is as effective as amphotericin B. An additional advantage is the possibility of oral application.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans

Invasive fungal infections are common in immunocompromised patients. Early diagnosis is still difficult and prophylactic modalities seems mandatory but are yet to be defined. Standard therapy of invasive fungal infections relies on the administration of intravenous amphotericin B. This agent is difficult to administer and toxic. Recently, new antifungal agents have been developed and are currently under investigation. Those new agents included itraconazole and fluconazole as well as new galenic preparations of amphotericin B such as liposomes. All these studies should provide optimal management of invasive fungal infections and improve the prognosis of those patients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Fluconazole; Humans; Itraconazole; Ketoconazole; Mycoses

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Meningitis; Recurrence

Cryptococcus neoformans has become an increasingly important pathogen. Cryptococcosis is an important cause of morbidity and mortality in immunocompromised hosts and is the second most common fungal infection complicating AIDS. In recent years, research has focused on the host defenses against Cryptococcus and has led to an improved understanding of the capsular virulence of the organism, the mechanisms of T-cell defenses, and the role of phagocytic cells in the fungistasis and killing of cryptocci. Amphotericin B with or without flucytosine has clearly improved treatment of cryptococcosis, but therapy is associated with significant toxicity. Current investigation is focused on the triazoles, which may offer improved therapy for cryptococcosis. In this report, we review recent developments in the understanding of the host defenses against Cryptococcocus and discuss current recommendations for the management of cryptococcosis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Immune Tolerance; Prognosis; Triazoles; Virulence

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections

Cutaneous cryptococcosis occurs in 10 to 15% of patients with cryptococcosis. Because the cutaneous crytpococcosis may precede clinical signs of central nervous system disease, early recognition may lead to more successful outcomes. This article reviews the mycology, epidemiology, pathology, clinical manifestations, and treatment of this disease, focusing primarily on the cutaneous aspects.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Biopsy; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Drug Therapy, Combination; Flucytosine; Humans; Immune Tolerance

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Histoplasmosis; Humans; Immune Tolerance; Immunity, Cellular; Mycoses; Opportunistic Infections

Genitourinary fungal infections have become increasingly common in clinical practice. We review the literature on such infections, emphasizing recognition of fungal disease, predisposing factors, pathogenesis, and approaches to therapy.

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Female; Genital Diseases, Female; Genital Diseases, Male; Histoplasmosis; Humans; Infant, Newborn; Male; Mycoses; Urinary Tract Infections

The deep mycoses are increasing in importance both as opportunistic infections and from exposure in geographically defined areas. Diagnosis may be difficult in both groups. Mucosal involvement may be non-specific (e.g., in disseminated candidiasis) or highly predictive of disseminated disease (e.g., histoplasmosis, blastomycosis and paracoccidioidomycosis). Skin involvement is generally uncommon in disseminated aspergillosis, mucormycosis and cryptococcosis but is more common in candidemia and coccidioidomycosis. Manifestations of mucosal and cutaneous lesions of the deep mycoses are reviewed and the need for an aggressive diagnostic approach stressed. Culture is more specific than histopathologic examination alone but the latter may have to suffice in some cases. Control of underlying disease and administration of amphotericin B remain the mainstays of therapy. Ketoconazole is being evaluated as an alternative in therapy of some deep mycoses.

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Candidiasis, Cutaneous; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Histoplasmosis; Humans; Immunosuppression Therapy; Ketoconazole; Miconazole; Mouth Diseases; Mouth Mucosa; Mucormycosis; Mycoses; Paracoccidioidomycosis; Sporotrichosis; Travel

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

Mycotic pneumonias are common problems seen in small companion animals because of the wide environmental distribution of fungi and their use of airborne spores for reproduction. This article outlines the important clinical features and pathogenesis of mycotic pneumonias and includes a detailed discussion of the therapeutic approach to patients with these infections.

Topics: Amphotericin B; Animals; Aspergillosis; Blastomycosis; Cat Diseases; Cats; Coccidioidomycosis; Cryptococcosis; Dog Diseases; Dogs; Histoplasmosis; Ketoconazole; Lung Diseases, Fungal; Pneumonia

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

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Imidazoles; Ketoconazole; Lung Diseases, Fungal; Miconazole; Mycoses; Nausea; Piperazines; Vomiting

The main antifungal agents used for deep-seated mycotic infections are the broad-spectrum antifungal drug amphotericin B, the narrow-spectrum agent flucytosine, and the newer broad-spectrum agents miconazole and ketoconazole. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. 2-Hydroxystilbamidine is used only in indolent cases of blastomycosis; however, this condition is usually treated with amphotericin B. Clinical experience with the newer agents is limited. Not all patients from whom fungal agents have been isolated require treatment; the extent of the fungal infection should be determined, when possible, for evaluation of the need for treatment.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cryptococcosis; Flucytosine; Humans; Imidazoles; Mycoses; Stilbamidines

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Imidazoles; Mucormycosis; Mycoses; Prognosis

Topics: Adult; Aged; Amphotericin B; Arthritis, Infectious; Cryptococcosis; Female; Flucytosine; Histoplasmosis; Humans; Male; Middle Aged

Topics: Amphotericin B; Animals; Cat Diseases; Cats; Cryptococcosis; Diagnosis, Differential; Female; Flucytosine; Male

Flucytosine is a systemic antifungal drug that is readily absorbed from the gastrointestinal tract. The most clearly documented therapeutic effect has been in cryptococcosis, candidiasis, and chromomycosis. An important limitation of the use of flucytosine in all three diseases has been drug resistance arising during therapy. The addition of low-dose, intravenous amphotericin B to flucytosine therapy of cryptococcosis has appeared to decrease the frequency of secondary flucytosine resistance. In addition, the two drugs have an additive or slightly synergistic effect against flucytosine susceptible isolates of Cryptococcus and Candida. The combination is probably the treatment of choice in cryptococcal meningitis and offers promise in the therapy of systemic candidiasis and nonmeningeal cryptococcosis.

Topics: Amphotericin B; Candidiasis; Chromoblastomycosis; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Mycoses

We reviewed the published reports of skeletal cryptococcosis and added three cases to the fifty-six in the literature. Eight of the patients in the reported cases probably did not have primary skeletal cryptococcosis. The potential toxicity of antifungal drugs in current use and the apparent effectiveness of surgical treatment for patients who only have a single focus of infection in bone, without involvement of other tissues, should be noted. The association of cryptococcosis with other diseases and the difficulty in differentiating purely skeletal involvement from more extensive disease are emphasized.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bone Diseases; Cryptococcosis; Diagnosis, Differential; Female; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Sarcoidosis

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candida; Candidiasis; Cryptococcosis; Humans; Lung Diseases, Fungal; Meningitis; Serologic Tests

Topics: Acute Disease; Adrenal Cortex Hormones; Amphotericin B; Aspergillosis; Blood Transfusion; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Iron; Leukemia; Leukemia, Lymphoid; Lymphoma; Mucor; Multiple Myeloma; Mycoses; Neutropenia; Rhizopus

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Complement Fixation Tests; Cryptococcosis; Fluorouracil; Histoplasmosis; Humans; Lung Diseases, Fungal; Skin Tests; Stilbamidines

Topics: Amphotericin B; Antifungal Agents; Child; Clotrimazole; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Estrogens; Female; Flucytosine; Humans; Immunologic Techniques; Male; Meningoencephalitis; Miconazole; Middle Aged; Phagocytosis; Rifampin; Transfer Factor

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Blastomycosis; Candicidin; Candidiasis; Coccidioidomycosis; Colistin; Cryptococcosis; Dermatomycoses; Drug Resistance, Microbial; Emetine; Flucytosine; Griseofulvin; Histoplasmosis; Humans; Imidazoles; Minocycline; Natamycin; Nystatin; Polyenes; Tolnaftate

Topics: Amphotericin B; Brain Diseases; Candidiasis; Coccidioidomycosis; Cryptococcosis; Herpes Zoster; Humans; Immunity, Cellular; Immunity, Maternally-Acquired; Leprosy; Lymphocyte Activation; Lymphokines; Male; Meningitis; Middle Aged; Subacute Sclerosing Panencephalitis; T-Lymphocytes; Tuberculosis; Wiskott-Aldrich Syndrome

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Infant, Newborn; Male; Meningitis; Pregnancy; Pregnancy Complications, Infectious

Topics: Actinomycosis; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Mucormycosis; Mycoses; Nocardia Infections; Sporotrichosis

Topics: Administration, Oral; Adolescent; Aged; Amphotericin B; Anemia; Anterior Chamber; Blastomycosis; Bronchi; Child; Cryptococcosis; Drug Resistance, Microbial; Fungi; Histoplasmosis; Humans; Injections; Injections, Intravenous; Injections, Spinal; Kidney Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Thrombophlebitis; Water-Electrolyte Balance

Topics: Amphotericin B; Cryptococcosis; Fluorescent Antibody Technique; Humans; Lung Diseases, Fungal; Radiography; Serologic Tests; Sputum

Topics: Amphotericin B; Aspergillosis; Candida; Candidiasis; Child; Child, Preschool; Coccidioidomycosis; Coccidiosis; Cryptococcosis; Endocarditis; Granuloma; Histoplasmosis; Humans; Infant; Kidney; Kidney Function Tests; Meningitis; Mycoses; Pneumonia

Topics: Amphotericin B; Animals; Columbidae; Communicable Disease Control; Cryptococcosis; Granuloma; Humans; Meningitis; Refuse Disposal

Topics: Actinomycosis; Adolescent; Adult; Amphotericin B; Animals; Aspergillosis; Basidiomycota; Blastomycosis; Candidiasis; Cephalosporins; Child; Chromoblastomycosis; Coccidioidomycosis; Conjunctiva; Cryptococcosis; Drug Synergism; Eye Diseases; Female; Fungi; Geotrichosis; Guinea Pigs; Histoplasmosis; Humans; Male; Mucor; Mycetoma; Mycoses; Natamycin; Nystatin; Penicillium; Pityriasis; Rabbits; Rhinosporidiosis; Sporotrichosis; Tinea

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Candidiasis; Cryptococcosis; Griseofulvin; Histoplasmosis; Humans; Nystatin; Penicillins

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Griseofulvin; Histoplasmosis; Humans; Iodides; Mucormycosis; Mycoses; Nocardia Infections; Nystatin; Penicillins; Sporotrichosis; Stilbamidines; Sulfadiazine; Surgical Procedures, Operative; Toxicology

Topics: Amphotericin B; Blastomycosis; Cryptococcosis; Histoplasmosis; Humans

Antifungal prophylaxis for liver transplant recipients (LTRs) is common among patients considered at high risk of infection, but optimal prophylaxis duration and drug has not been defined. This study aimed to assess the effects of 14 days of antifungal therapy prophylaxis in reducing proven invasive fungal infections (IFI) in high-risk subjects. Eligible subjects who met 2 or more risk criteria were randomized 1:1 to the treatment arms (liposomal amphotericin B or fluconazole) and were followed for 100 days post transplantation for evidence of IFI. The study was designed to enroll 300 subjects, but was closed early for insufficient enrollment. A total of 71 subjects were enrolled and randomized. Two-thirds of subjects completed 14 days of study therapy. Ten subjects developed proven or probable IFI with Candida species (9 subjects) and Cryptococcus neoformans (1 subject); rates were similar in the 2 treatment arms. Eleven subjects died, but no death was attributed to study drug or IFI. In summary, high-risk LTRs tolerated antifungal prophylaxis well, and rates of IFI were lower than previously reported in untreated high-risk LTRs.

Topics: Adult; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candida; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Double-Blind Method; Female; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Mycoses; Treatment Outcome

The combination of flucytosine and amphotericin B is first choice treatment for active cryptococcosis. Because of innate or acquired resistance of Cryptococcus neoformans to flucytosine, in vitro testing is mandatory. Yeast nitrogen base (YNB) at pH 7.0 is the recommended medium for the broth microdilution test (NCCLS M27-A) and for the E-test. In order to verify if minimum inhibitory concentrations (MICs) were able to predict treatment outcome, the susceptibility of 24 isolates from 21 patients treated with flucytosine alone or in combination was tested by the broth microdilution, agar dilution and E-test using YNB either at pH 7.0 or at pH 5.4. Only those MICs obtained on YNB pH 5.4 proved to correlate with treatment outcome. The present study suggests that in vitro susceptibility to flucytosine of C. neoformans isolates should be evaluated on YNB pH 5.4 and the test should be standardized accordingly.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Culture Media; Drug Therapy, Combination; Female; Flucytosine; Humans; Hydrogen-Ion Concentration; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcosis; Fluconazole; Flucytosine; Humans; Male

The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Creatinine; Cryptococcosis; Drug Combinations; Female; Humans; Male; Mycoses; Phosphatidylcholines; Phosphatidylglycerols

The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v. plus flucytosine at doses of 100 mg kg-1 day-1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o. indefinitely. During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up. The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Chronic Disease; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Follow-Up Studies; Humans; Itraconazole; Meningitis, Cryptococcal

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Female; Fluconazole; Follow-Up Studies; Humans; Itraconazole; Male; Meningitis, Cryptococcal; Middle Aged; Reproducibility of Results

To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis.. A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented.. Hospital-based HIV units.. Twenty-three HIV-1-seropositive patients.. Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically.. AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Body Fluids; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; HIV-1; Humans; Leukocyte Count; Life Tables; Liposomes; Male; Meningitis, Cryptococcal; Middle Aged; Survival Analysis

To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis.. Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses.. Los Angeles County-University of Southern California Medical Center.. Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis.. Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27).. Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis; Opportunistic Infections; Prospective Studies; Randomized Controlled Trials as Topic

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

Because of the increasing numbers of patients with acquired immunodeficiency syndrome (AIDS) who will require treatment for cryptococcosis and because of the problems associated with long-term administration of intravenous amphotericin B, an alternative therapeutic approach in the form of an efficacious and easily administered oral antifungal drug would be of great benefit. Fluconazole, a new triazole antifungal agent, represents such an alternative. We therefore conducted an open, non-randomized trial of oral fluconazole as maintenance suppressive therapy of disseminated cryptococcosis in patients with AIDS.. Twenty patients with AIDS, 19 of whom had cryptococcal meningitis, were studied. Patients were followed for up to 21 months. All patients received amphotericin B as primary therapy, from 20 to 257 days prior to entry (500 to 5,080 mg total dose). Eight also received flucytosine. After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, Cryptococcus neoformans was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient. Fluconazole was given once daily, in doses of 50 to 200 mg/day.. Following initiation of fluconazole, results of CSF and blood cultures continued to be negative, except for the CSF culture in one patient who had a relapse in the 32nd week of therapy. Fluconazole therapy has been successfully continued in nine patients, for a median of 11 months (nine to 21 months). Seven patients died; five had no evidence of active cryptococcosis at the time of death. Two patients had a relapse, although the CSF culture showed growth of the fungus in only one patient. One patient was lost to follow-up after five months of therapy and one was unevaluable. Fluconazole had to be discontinued in only one patient in whom thrombocytopenia developed, and then resolved when the drug was stopped.. We conclude that oral fluconazole represents a significant advance in the management of cryptococcal meningitis and should be useful in the long-term suppressive therapy of this opportunistic infection in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Antigens, Fungal; Clinical Trials as Topic; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Male; Triazoles

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antigens, Fungal; Child; Clinical Trials as Topic; Cryptococcosis; Drug Administration Schedule; Drug Therapy, Combination; Female; Flucytosine; Heart Transplantation; Humans; Kidney Transplantation; Male; Meningitis; Middle Aged; Prospective Studies; Random Allocation; Recurrence

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Child; Clinical Trials as Topic; Creatinine; Cryptococcosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Flucytosine; Humans; Male; Meningitis; Middle Aged; Prospective Studies; Random Allocation; Time Factors

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Topics: Adolescent; Adult; Aged; Amphotericin B; Cryptococcosis; Cytosine; Drug Evaluation; Drug Therapy, Combination; Flucytosine; Humans; Meningitis; Middle Aged; Prospective Studies; Time Factors

Therapeutic effectiveness of 5-fluorocytosine (5-FC), amphotericin B (Am B) and both in combined administration were retrospectively assessed and compared with one another in 28 patients with cryptococcal meningitis. Combined administration was significantly superior to Am B alone and to 5-FC alone, and these agents were suggested to afford a synergetic effect in combined administration. Adverse reactions associated with combined administration did not essentially differ from those with Am B or 5-FC alone. Combined administration was able to decrease the incidence and severity of adverse reactions by employing lower doses of Am B, and this combined administration reduced the duration of treatment. An appropriate dose for each agent in combined administration was deemed to be about 0.350 mg/kg/day Am B i.v. and 150 mg/kg/day 5-FC p. o. based on the results of this study.

Topics: Adult; Aged; Amphotericin B; Clinical Trials as Topic; Cryptococcosis; Cytosine; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Flucytosine; Gastrointestinal Diseases; Hematologic Diseases; Humans; Injections, Intravenous; Male; Meningitis; Middle Aged; Time Factors

Topics: Adult; Amphotericin B; Blastomycosis; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Male; Middle Aged; Sporotrichosis

The simultaneous occurrence of cerebral toxoplasmosis and cryptococcosis is rare. The infections continue to be treated with sulfadiazine and amphotericin-B-based regimens (preferred therapy), respectively. Both these drugs are linked to some serious adverse drug reactions (ADRs). We report such a unique instance of both; the CNS co-infections and adverse drug reactions to the preferred therapy.. A 44-year-old Asian-Indian female was diagnosed with cerebral toxoplasmosis, impending cryptococcal meningoencephalitis, and acquired immune deficiency syndrome (AIDS). The preferred therapy of opportunistic CNS co-infections commenced. Within a week, she had an occurrence of fall in hemoglobin concentrations (11.3 g/dL to 5.6 g/dL; grade IV), reticulocytosis (1% to 3.2%), and indirect hyperbilirubinemia (0.5 mg/dL to 2.8 mg/dL; grade IV) after sulfadiazine administration. The drug was discontinued and the patient was treated with hematocrit transfusions. After amphotericin-B deoxycholate (AmBd) administration, the patient developed hypokalemia (serum potassium; 4.5 mmol/L to 2.7 mmol/L) and increased serum creatinine (1.0 to 2.2 mg/dL; stage-I) levels. Hence, AmBd was discontinued and potassium correction was given. The patient got diagnosed with sulfadiazine induced hemolytic anemia and AmBd induced acute renal failure. He was switched to alternative therapy regimens for the treatment of cerebral toxoplasmosis and cryptococcosis. Radiological investigations were followed up to confirm the clinical outcomes of alternative therapy. Complete recovery from the ADRs and opportunistic infections was observed.. The preferred therapy regimens for toxoplasmosis and cryptococcosis are accompanied by potential adverse drug reactions, thus continuous monitoring is vital, especially in the initial phases of therapy. Discontinuation of the treatment should be the preliminary intervention in the management. Having said that, alternative therapy regimens had an optimal clinical response in the present case.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Potassium; Sulfadiazine; Toxoplasmosis, Cerebral

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Microbial Sensitivity Tests; Peptides; Structure-Activity Relationship

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.. This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Cryptococcosis; Female; Humans; Lipids; Male; Organ Transplantation; Retrospective Studies

Cryptococcus gattii and Cryptococcus neoformans are the main etiological agents of cryptococcosis, an invasive mycosis treated with amphotericin B, 5-fluorocytosine, and fluconazole. This limited arsenal is toxic and is associated with antifungal resistance. Cryptococcosis and malaria pathogens are eukaryotic organisms that have a high incidence in Sub-Saharan Africa. The antimalarials (ATMs) halofantrine (HAL) and amodiaquine (AQ) block Plasmodium heme polymerase, and artesunate (ART) induces oxidative stress. Considering that Cryptococcus spp. is susceptible to reactive oxygen species and that iron is essential for metabolism, the repurposing of ATMs for treating cryptococcosis was tested. ATMs reduced fungal growth, induced oxidative and nitrosative stresses, and altered ergosterol content, melanin production, and polysaccharide capsule size in C. neoformans and C. gattii, revealing a dynamic effect on fungal physiology. A comprehensive chemical-genetic analysis using two mutant libraries demonstrated that the deletion of genes involved in synthesizing components of the plasma membrane and cell wall, and oxidative stress responses are essential for fungal susceptibility to ATMs. Interestingly, the amphotericin B (AMB) fungicidal concentrations were ∼10 times lower when combined with ATMs, demonstrating a synergistic interaction. Further, the combinations showed reduced toxicity to murine macrophages. Finally, HAL+AMB and AQ+AMB efficiently reduced lethality and fungal burden in the lungs and brain in murine cryptococcosis. These findings provide perspectives for further studies with ATMs against cryptococcosis and other fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Antimalarials; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Fluconazole; Mice; Microbial Sensitivity Tests

Here we tested the correlation between minimum inhibitory concentrations (MICs) of major antifungal agents and sequence types (STs) within Cryptococcus neoformans VNI isolates, and explored the ERG11 gene of included strains.. We analysed 23 C. neoformans strains categorised into two groups according to the distribution of the ST profile in Kinshasa clinics (Democratic Republic of Congo): major ST [ST93 (n = 15)], and less common STs [ST659 (n = 2), ST5 (n = 2), ST4 (n = 1), ST 53 (n = 1), ST31 (n = 1), and ST69 (n = 1)]. The MICs of the major antifungal agents [amphotericin B (AMB), 5-fluorocytosine (5FC) and fluconazole (FCZ)] were determined following EUCAST guidelines. ERG11 gene sequences were extracted from whole genome sequence of the isolates and compared with the wild-type gene sequence of the C. neoformans VNI.. Although major ST isolates appeared to have lower median MICs for AMB and 5FU than less common ST isolates (0.50 vs. 0.75 mg/L for AMB, 2 vs. 4 mg/L for 5FU, respectively), FCZ susceptibility was similar in both groups (4 mg/L) (p-value >0.05). The susceptibility profile of C. neoformans strains separately considered did not significantly affect the patients' clinical outcomes (p-value >0.05). Furthermore, two structural modalities of the ERG11 gene were observed: (1) that of the reference gene, and (2) that containing two exonic silent point substitutions, and one intronic point substitution located in a sequence potentially involved in pre-mRNA splicing (c.337-22C > T); with no association with the MICs of the isolates (p-value >0.05).. The lack of association/correlation found in this study calls for further investigations to better understand the mechanisms of C. neoformans resistance to antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Democratic Republic of the Congo; Drug Resistance, Fungal; Fluconazole; Flucytosine; Fluorouracil; HIV Infections; Humans; Microbial Sensitivity Tests; Polymorphism, Genetic

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Meningitis, Cryptococcal; Meningoencephalitis; Mice

DectiSomes are anti-infective drug-loaded liposomes targeted to pathogenic cells by pathogen receptors including the Dectins. We have previously used C-type lectin (CTL) pathogen receptors Dectin-1, Dectin-2, and DC-SIGN to target DectiSomes to the extracellular oligoglycans surrounding diverse pathogenic fungi and kill them. Dectin-3 (also known as MCL, CLEC4D) is a CTL pathogen receptor whose known cognate ligands are partly distinct from other CTLs. We expressed and purified a truncated Dectin-3 polypeptide (DEC3) comprised of its carbohydrate recognition domain and stalk region. We prepared amphotericin B (AmB)-loaded pegylated liposomes (AmB-LLs) and coated them with this isoform of Dectin-3 (DEC3-AmB-LLs), and we prepared control liposomes coated with bovine serum albumin (BSA-AmB-LLs). DEC3-AmB-LLs bound to the exopolysaccharide matrices of Candida albicans, Rhizopus delemar (formerly known as R. oryzae), and Cryptococcus neoformans from one to several orders of magnitude more strongly than untargeted AmB-LLs or BSA-AmB-LLs. The data from our quantitative fluorescent binding assays were standardized using a CellProfiler program, AreaPipe, that was developed for this purpose. Consistent with enhanced binding, DEC3-AmB-LLs inhibited and/or killed C. albicans and R. delemar more efficiently than control liposomes and significantly reduced the effective dose of AmB. In conclusion, Dectin-3 targeting has the potential to advance our goal of building pan-antifungal DectiSomes.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Cryptococcosis; Humans; Liposomes

Cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis and cryptococcal meningitis, which conventional treatment involves antifungal drugs such as polyenes, flucytosine, azoles, and their combinations. However, the high cost, toxicity, and increase in fungi resistance to antifungal agents stimulate the search for therapeutic strategies such as drug repurposing and combination therapy. This study evaluated the activity of the antihypertensive verapamil (VEH) alone and combined with amphotericin B (AmB) against C. neoformans. VEH exhibited antifungal activity against C. neoformans with minimum inhibitory concentration and minimum fungicidal concentration of 118 µg per mL. The combination of VEH and AmB exhibited synergism, reducing at least eightfold both drugs' concentrations. Moreover, the combination decreased the size and glucuronoxylomannnan content of C. neoformans capsule. However, no difference was observed in ergosterol levels of C. neoformans after treatment with VEH and AmB in combination. Altogether, VEH in combination with AmB exhibits potential as a candidate as for the development of anti-cryptococcal drug.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Microbial Sensitivity Tests

BACKGROUND Pulmonary cryptococcosis is an uncommon infection mainly affecting immunocompromised individuals. Presentation of cryptococcal disease ranges from asymptomatic pulmonary colonization to severe pneumonia. It can progress to acute respiratory failure and life-threatening meningoencephalitis. CASE REPORT A 55-year-old woman with a history of a kidney transplant, on immunosuppressive therapy, presented to the hospital with persistent low-grade fever, headache, weight loss, and fatigue for 2 weeks. On arrival, she was tachycardic, normotensive, and saturating 99% on room air. Her chest X-ray showed right middle lung opacity measuring 1.9×2.8 cm. She was admitted and started on broad-spectrum antibiotics for suspected pneumonia. Her chest computed tomography (CT) scan showed a 3.0×1.7 cm hypo-dense opacity at the right upper lobe. Overnight, she developed a severe headache and neck stiffness. Her serum cryptococcal antigen and cerebrospinal fluid culture results were positive. The patient was started on intravenous liposomal amphotericin B plus flucytosine. A CT-guided lung biopsy was performed to rule out malignancy. Cultures came back positive for Cryptococcus neoformans. She completed a 2-week course of amphotericin and flucytosine and was switched to oral fluconazole to complete an 8-week course. CONCLUSIONS Prompt diagnosis and effective management of the cryptococcal disease can decrease morbidity and mortality. Diagnosis requires CT-guided lung biopsy, with culture growing mucoid colonies of Cryptococcus neoformans. Antifungal therapy with intravenous liposomal amphotericin B plus flucytosine is the mainstay of treatment. Clinicians should be aware of the various presentations of pulmonary cryptococcosis, especially in immunocompromised patients.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; Headache; Humans; Immunocompromised Host; Lung; Middle Aged

Topics: Adaptation, Physiological; Amphotericin B; Aneuploidy; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Microbial Sensitivity Tests; Serogroup

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

Cryptococcus neoformans is a yeast that mainly affects immunocompromised individuals and causes meningoencephalitis depending on the immune status of the host. The present study aimed to validate the efficacy of selective serotonin reuptake inhibitors, fluoxetine hydrochloride (FLH) and paroxetine hydrochloride (PAH), alone and in combination with amphotericin B (AmB) against C. neoformans. Susceptibility tests were conducted using the broth microdilution method and synergistic effects of combining FLH and PAH with AmB were analyzed using the checkerboard assay. Effects of minimum inhibitory concentration (MIC) and synergistic concentration were evaluated in biofilms by quantifying the biomass, measuring the viability by counting the colony-forming units (CFU/mL) and examining the size of the induced capsules. Cryptococcus neoformans was susceptible to FLH and PAH and the synergistic effect of FLH and PAH in combination with AmB reduced the MIC of AmB by up to 8-fold. The isolated substances and combination with AmB were able to reduce biofilm biomass and biofilm viability. In addition, FLH and PAH alone or in combination with AmB significantly decreased the size of the yeast capsules. Collectively, our results indicate the use of FLH and PAH as a promising prototype for the development of anti-cryptococcal drugs.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Drug Therapy, Combination; Fluoxetine; Humans; Meningoencephalitis; Microbial Sensitivity Tests; Microbial Viability; Paroxetine; Selective Serotonin Reuptake Inhibitors

Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of antifungals allowed the selection of resistant pathogens posing threats to global public health. Histone deacetylase genes are involved in Cryptococcus virulence, and in pathogenicity and resistance to azoles in Candida albicans. Aiming to assess whether histone deacetylase genes are involved in antifungal response and in synergistic drug interactions, we evaluated the activity of amphotericin B, fluconazole, sulfamethoxazole, sodium butyrate or trichostatin A (histone deacetylase inhibitors), and hydralazine or 5- aza-2'-deoxycytidine (DNA methyl-transferase inhibitors) against different Cryptococcus neoformans strains, C. neoformans histone deacetylase null mutants and Cryptococcus gattii NIH198. The drugs were employed alone or in different combinations. Fungal growth after photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion, alone or in combination with the aforementioned drugs, was assessed for the C. neoformans HDAC null mutant strains. Our results showed that fluconazole was synergistic with sodium butyrate or with trichostatin A for the hda1Δ/hos2Δ double mutant strain. Sulfamethoxazole was synergistic with sodium butyrate or with hydralazine also for hda1Δ/hos2Δ. These results clearly indicate a link between HDAC impairment and drug sensitivity. Photodynamic therapy efficacy on controlling the growth of the HDAC mutant strains was increased by amphotericin B, fluconazole, sodium butyrate or hydralazine. This is the first study in Cryptococcus highlighting the combined effects of antifungal drugs, histone deacetylase or DNA methyltransferase inhibitors and photodynamic therapy in vitro.

Topics: Amphotericin B; Antifungal Agents; Bacterial Proteins; Butyric Acid; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Emulsions; Epigenesis, Genetic; Fluconazole; Gene Expression Regulation, Bacterial; Histone Deacetylases; Humans; Hydroxamic Acids; Indoles; Nanoparticles; Organometallic Compounds; Photochemotherapy; Sulfamethoxazole

Amphotericin B (AmB) is a very effective antifungal agent, and resistance in clinical isolates is rare. However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB-rimonabant polytherapies for fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidemia; Cell Membrane Permeability; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Fungi; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Oxidative Stress; Rimonabant; Small Molecule Libraries

Crazy-paving patterns are rarely reported as radiological manifestations of pulmonary cryptococcosis.. Herein, we presented a very rare case of a crazy-paving pattern as a radiological manifestation of pulmonary cryptococcosis in a patient with primary ciliary dyskinesia. The diagnosis of pulmonary cryptococcosis and primary ciliary dyskinesia was ultimately confirmed by bronchoscopic biopsy, fungus culture, whole exome sequencing of blood, etc. The patient received flucytosine (PO, 5 g per day) and amphotericin B (IV, 70 mg per day) during hospitalization and sequential therapy with voriconazole (PO, 200 mg twice a day) after discharge. He recovered during follow-up.. We concluded that pulmonary cryptococcosis should be considered a possible cause of crazy-paving patterns in chest CT scans.

Topics: Amphotericin B; Antifungal Agents; Bronchoscopy; Cryptococcosis; Flucytosine; Humans; Lung Diseases, Fungal; Male; Middle Aged; Tomography, X-Ray Computed; Voriconazole

Cryptococcus is an encapsulated yeast that causes fungal meningitis, most commonly in HIV patients, with high mortality rates. Thus, the study of new treatment options is relevant. Antifungal activity of organoselenium compounds attributed to their pro-oxidative effect in fungal cells has been shown given that few data regarding its anti-Cryptococcus activity are available, this in vitro study was conducted with 40 clinical isolates of Cryptococcus neoformans. Diphenyl diselenide (DD) alone, and its interaction with amphotericin B or fluconazole, was tested by microdilution and checkerboard assays. All Cryptococcus neoformans were inhibited by DD in concentrations ≤ 32 μg/mL, and fungicidal concentrations were ≤ 64 μg/mL. Advantageous interaction between fluconazole occurred in 40% of the isolates, respectively. This study contributes with data of DD alone and in combination with classical drugs of choice for cryptococcosis treatment. Further studies focused on DD antifungal mechanism of action, and in vivo experiments are necessary.

Topics: Amphotericin B; Antifungal Agents; Benzene Derivatives; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Microbial Sensitivity Tests; Organoselenium Compounds

Amphotericin B (AmB) is used to treat cryptococcal meningoencephalitis. However, the mortality rate remains high. Higher doses of AmB in deoxycholate buffer (AmBd) are toxic to human red blood cells (hRBC) and have no effect on brain organism load in mice. Here we show that while AmBd lysed 96% of hRBC, AmB complexed with gold nanoparticles (AuNP-SA-AmB) lysed only 27% of hRBC. In vitro growth of C. neoformans was inhibited by 0.25 μg/ml AmBd and 0.04 μg/ml of AuNP-SA-AmB. In mice infected with C. neoformans, five daily treatments with AuNP-SA-AmB containing 0.25 mg/kg AmB significantly lowered the fungal burden in the brain tissue compared to either untreated or treatment with 0.25 mg/kg of AmBd. When a single dose of AmBd was injected intravenously into BALB/c mice, 81.61% of AmB cleared in the α-phase and 18.39% cleared in the β-phase at a rate of 0.34% per hour. In contrast, when AuNP-SA-AmB was injected, 49.19% of AmB cleared in the α-phase and 50.81% of AmB cleared in the β-phase at a rate of 0.27% per hour. These results suggest that AmB complexed with gold nanoparticles is less toxic to hRBC, is more effective against C. neoformans and persists longer in blood when injected into mice resulting in more effective clearing of C. neoformans from the brain tissue.. Amphotericin B (AmB) was complexed with gold nanoparticles (AuNP-SA-AmB) to improve brain delivery. AuNP-SA-AmB was more effective than AmB alone in clearing of Cryptococcus neoformans from the brain tissue of infected mice. This may be due to longer plasma half-life of AmB as AuNP-SA-AmB.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain Diseases; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Erythrocytes; Gold; Humans; Mice; Rodent Diseases

X-linked hyper-IgM syndrome (XHIM) caused by CD40L mutations is a primary immunodeficiency condition that increases susceptibility to opportunistic infections. Disseminated cryptococcosis in XHIM is rarely reported in children. Here, we report two related boys who have a novel hemizygous frameshift c.208delC mutation of CD40L. They live in the western region of Thailand and developed disseminated cryptococcosis while receiving regular intravenous immunoglobulin supplementation.

Topics: Amphotericin B; Antifungal Agents; CD40 Ligand; Child; Cryptococcosis; Fluconazole; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulins, Intravenous; Male; Mutation

Iron chelator has previously demonstrated fungicidal effects. This study aimed to investigate the antifungal activity of the iron chelators deferoxamine (DFO) and deferasirox (DSX) against Cryptococcus.. Cryptococcus neoformans and Cryptococcus gattii were used to determine the minimal inhibitory concentrations (MICs) of DFO and DSX, and the fractional inhibitory concentration index (FICI) of DFO and DSX when combined with amphotericin B (AMB). Expression of cryptococcal CFT1, CFT2, and CIR1 genes was determined using real-time polymerase chain reaction (PCR).. Neither DFO nor DSX alone showed antifungal activity against Cryptococcus strains. When combined with AMB, the MICs of DFO and DSX decreased from>200μg/mL to 6.25 or 12.5μg/mL. The MIC of AMB decreased one-fold dilution in most strains when combined with iron chelators. The FICI of DFO+AMB and DSX+AMB was 0.5 and 1, respectively. C. neoformans showed significant growth retardation when incubated with a combination of sub-MIC concentrations of AMB and DFO; whereas, C. gattii demonstrated lesser growth retardation in DFO+AMB. No cryptococcal growth retardation was observed when DSX was combined with AMB. When C. neoformans was grown in DFO, the CFT1, CFT2, and CIR1 proteins were expressed 1.7, 2.0, and 0.9 times, respectively. When C. neoformans was grown in DSX, the CFT1, CFT2, and CIR1 genes were expressed 0.5, 0.6, and 0.3 times, respectively.. Synergistic antifungal activity of combination DFO and AMB was observed in Cryptococcus. Relatively increased CFT1 and CFT2 expression may be associated with the effect of DFO that inhibits the growth of fungi.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Deferasirox; Deferoxamine; Drug Synergism; Fungal Capsules; Gene Expression Regulation, Fungal; Humans; Invasive Fungal Infections; Iron; Iron Chelating Agents; Iron Overload; Metabolic Networks and Pathways; Microbial Sensitivity Tests; Virulence Factors

Cryptococcosis is a common opportunistic infection in patients with advanced HIV infection and may also affect immunocompetent patients. The available antifungal agents are few and other options are needed for the cryptococcosis treatment. In this work, we first analyzed the virulence of twelve C. neoformans and C. gattii strains assessing capsule thickness, biofilms formation, and survival and morbidity in the invertebrate model of Galleria mellonella and then we evaluated the antifungal activity of voriconazole (VRC) in vitro and in vivo also using G. mellonella. Our results showed that all Cryptococcus spp. isolates were able to produce capsule and biofilms, and were virulent using G. mellonella model. The VRC has inhibitory activity on planktonic cells with MIC values ranging from 0.03 to 0.25 μg/mL on Cryptococcus spp.; and these isolates were more tolerant to fluconazole (ranging from 0.25 to 16 μg/mL), the triazol agent often recommended alone or in combination with amphotericin B in the cryptococcosis therapy. In contrast, mature biofilms were less susceptible to the VRC treatment. The VRC (10 or 20 mg/kg) treatment of infected G. mellonella larvae significantly increased the larval survival when compared to the untreated group for the both Cryptococcus species and significantly decreased the fungal burden and dissemination in the larval tissue. Our findings corroborate with the literature data, supporting the potential use of VRC as an alternative for cryptococcosis treatment. Here, we emphasize the use of G. mellonella larval model as an alternative animal model for studies of antifungal efficacy on mycosis, including cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Cryptococcosis; Cryptococcus gattii; Disease Models, Animal; Fluconazole; Humans; Larva; Microbial Sensitivity Tests; Moths; Voriconazole

Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis.

Topics: Acetylcysteine; Amphotericin B; Animals; Antifungal Agents; Brain; Creatinine; Cryptococcosis; Cryptococcus; Deoxycholic Acid; Disease Models, Animal; Drug Combinations; Drug Repositioning; Female; Kidney; Lung; Macrophages; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Reactive Oxygen Species

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud's dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.

Topics: Adenocarcinoma; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Immunocompromised Host; Male; Prostatic Neoplasms

Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that have a minor effect on

Topics: Amphotericin B; Animals; Antifungal Agents; Auranofin; Candida albicans; Candidiasis; Cell Line; Ciclopirox; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation, Preclinical; Drug Repositioning; Drug Synergism; Erythromycin; Flucytosine; Humans; Mice; Microbial Sensitivity Tests; Opportunistic Infections; RAW 264.7 Cells; Zebrafish

The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs.. A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved.. This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.

Topics: Acyclovir; Amphotericin B; Autoantibodies; Coinfection; Cryptococcosis; Fluconazole; Herpesvirus 3, Human; Humans; Immunologic Deficiency Syndromes; Interferon-gamma; Lymphadenopathy; Male; Middle Aged; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Varicella Zoster Virus Infection

Brain infections with

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Fluconazole; Meningitis, Cryptococcal; Mice

Pulmonary cryptococcosis develops not only in immunocompromised patients but also in immunocompetent patients. However, lymph node involvement is relatively rare in immunocompetent patients. We herein report the case of an 80-year-old man who was not in an apparent immunocompromised state but was diagnosed with pulmonary cryptococcosis with mediastinal lymphadenopathy. The patient was resistant to fluconazole and voriconazole monotherapy; thus, his lung lesions significantly worsened. He eventually responded well to a combination therapy of amphotericin B and flucytosine, which was administered according to the treatment strategy for disseminated diseases.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Drug Tolerance; Flucytosine; Humans; Lymphadenopathy; Male; Respiratory Tract Infections

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB). Brown, red or black melanin pigments can be produced by the polyketide pathway (DHN-melanin) or from dihydroxyphenols, such as L-DOPA (L-3,4-dihydroxyphenylalanine) and L-tyrosine by polyphenoloxidases. Among several pathogenic fungi, Cryptococcus neoformans is a melanized yeast that causes pneumonia and meningoencephalitis in immunocompromised patients. The knockout of the laccase genes or other interruptions on melanin biosynthetic pathway generates cryptococcal strains with attenuated virulence in an animal model. In this study 16 analogues of coumaric and cinnamic acid were evaluated as possible tyrosinase inhibitors. We have identified some valuable inhibitors of C. neoformans growth and melanin biosynthesis disruption agents. The results showed that coumaric acid derivatives (1a-c), the ketones (3a-b) and 2-allylphenol (7c) are significant inhibitors of tyrosinase and melanization of the fungus. Two analogues (1b and 3b) were selected as promising antimelanogenic agents to be combined with AmB, showing to promote 16-fold reduction in the AmB fungicidal concentration with no appreciable cytotoxicity to mammalian cells. The data suggest that inhibition of the melanin biosynthesis by these compounds may increase the susceptibility of the cells to the oxidative stress generated by AmB. In summary, our data show that C. neoformans can be a suitable model system to test novel inhibitors that target melanin biosynthesis, and novel compounds for adjunct therapy against C. neoformans were identified.

Topics: Amphotericin B; Animals; Antifungal Agents; Coumaric Acids; Cryptococcosis; Cryptococcus neoformans; Humans; Melanins

The purpose of this case report was to report a case of Cryptococcus laurentii infection in the left knee of a previously healthy 29 year old male patient.. After an initial misdiagnosis and 7 months of failed treatment, the patient received nearly a month of treatment with voriconazole (200 mg IV q12 h) and knee irrigation with amphotericin B until the infection was controlled. The treatment continued with fluconazole for nearly 7 months and approximately 5 weeks of antibiotic treatment for a skin bacterial coinfection. In the end, the patient's symptoms disappeared completely, the left knee recovered well, and there was no recurrence of infection.. The key points of successful treatment in this case were the thorough debridement, the adequate course of knee irrigation with antifungal drugs and more than 6 months of oral antifungal drugs that were able to eradicate the infection.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Cryptococcosis; Cryptococcus; Debridement; Diagnostic Errors; Fluconazole; Focal Infection; Humans; Knee; Male; Skin Diseases, Bacterial; Voriconazole

Idiopathic CD4 lymphocytopenia (ICL) is a rare disease characterized by marked loss of CD4 T-cells without human immunodeficiency virus infection. CD4 T-cells play an important role in granuloma formation in cryptococcal infection. Thus far, among ICL patients, it has not been concluded definitely whether granuloma is formed or not. We report the case of a 39-year-old woman with ICL and disseminated cryptococcal infection with granuloma formation. She was referred to our department because of a lung mass, osteolytic lesion, and a subcutaneous mass identified on a computed tomography scan, and an elevated C-reactive protein level. Cryptococcus neoformans was isolated from the tissues. She also had marked CD4 lymphocytopenia (33 cells/μL), without human immunodeficiency virus infection. In a biopsy specimen of the lung mass, granulomas containing CD4 T-cells were observed. The cryptococcosis was treated with liposomal amphotericin B followed by fluconazole and she was found to be cured. The CD4 T-cell count was persistently low. This case showed that granulomas containing CD4 T-cells can be formed in ICL patients with cryptococcal infection despite very low CD4 T-cell counts.

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; CD4 Lymphocyte Count; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Granuloma; Humans; Lung; Sjogren's Syndrome; T-Lymphocytopenia, Idiopathic CD4-Positive; Tomography, X-Ray Computed; Treatment Outcome

We found a novel role of Myo5, a type I myosin (myosin-I), and its fortuitous association with d-amino acid utilization in

Topics: Actins; Amino Acids; Amphotericin B; Antifungal Agents; Cell Membrane; Cell Membrane Permeability; Cryptococcosis; Cryptococcus gattii; Endocytosis; Flucytosine; Fungal Proteins; Humans; Mutation; Myosin Type I; Phenotype

Topics: Administration, Intravenous; Administration, Oral; Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cellulitis; Cryptococcosis; Cryptococcus gattii; Debridement; Fluconazole; Humans; Immunocompromised Host; Male; Treatment Outcome

Genetic diversity analyses were performed by sero-genotyping and multi-locus sequence typing on 252 cryptococcal isolates from 13 HIV-positive Ivorian patients followed-up for cryptococcal meningitis. Antifungal susceptibility analyses were performed according to the CLSI M27A3 method. The majority (67.8%) of the isolates belonged to the Cryptococcus neoformans (serotype A) species complex, with 93% being VNI and 7% being VNII. Cryptococcus deuterogattii VGII (serotype B) represented 16.7% of the strains, while C. neoformans/C. deneoformans VNIII (serotype AD) hybrids accounted for 15.1% of the strains. One strain (0.4%) was not identifiable. Nine different sequence types (STs 5, 6, 23, 40, 93, 207, 311, and a new ST; 555) were identified in the C. neoformans population, while the C. deuterogattii population comprised the single ST 173. The distribution of the strains showed that, while the majority of patients (9/13) harboured a single sequence type, 4 patients showed mixed infections. These patients experienced up to 4 shifts in strain content either at the species and/or ST level during their follow-up. This evolution of diversity over time led to the co-existence of up to 3 different Cryptococcus species and 4 different ST within the same individual during the course of infection. Susceptibility testing showed that all strains were susceptible to amphotericin B while 3.6% of them had a none-wild type phenotype to 5-flucytosine. Concerning fluconazole, 2.9% of C.neoformans serotype A strains and 2.4% of C. deuterogattii had also respectively a none-wild type phenotype to this molecule. All C. neoformans x C. deneoformans serotype AD hybrids had however a wild type phenotype to fluconazole. The present study showed that mixed infections exist and could be of particular importance for care outcomes. Indeed, (i) the different Cryptococcus species are known to exhibit different virulence and different susceptibility patterns to antifungal drugs and (ii) the strains genetic diversity within the samples may influence the susceptibility to antifungal treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; Follow-Up Studies; Genetic Variation; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Mycological Typing Techniques

Cryptococcosis following kidney transplantation (KT) is rare but is associated with considerably increased risk of mortality. At present, data on the association between cryptococcosis and KT in mainland China remain relatively limited.. This study aims to review our experience related to the management of cryptococcosis following KT at a Chinese tertiary hospital.. All patients with cryptococcosis following KT admitted to our hospital from January 2010 to December 2018 were reviewed.. A total of 37 patients with cryptococcosis were enrolled (males: 62.2%). The mean age of the patients was 49.5 ± 9.38 (20-64) years. The average time to infection following KT was 7.0 ± 5.50 years (5 months to 21 years), and 30 patients (81.1%) had cryptococcosis onset >2 years following transplantation. The most common site of infection was the central nervous system, followed by the pulmonary system and skin. Most patients received fluconazole or voriconazole with or without flucytosine as their initial treatment regimen at our hospital. The 2-week mortality rate was 8.1% (3/37), and five patients (13.5%) died within 6 months of being diagnosed with cryptococcosis. Remarkably, all patients who received high-dose fluconazole (800 mg daily) or voriconazole ± flucytosine survived.. Cryptococcosis in kidney transplant recipients is typically a late-occurring infection, with most patients having cryptococcosis onset >2 years following KT at our hospital. The central nervous system, pulmonary system, and skin are the main sites of infection. Voriconazole or high-dose fluconazole can be used as an alternative therapy for post-KT cryptococcosis.

Topics: Adult; Amphotericin B; Antifungal Agents; China; Cryptococcosis; Cryptococcus; Female; Fluconazole; Humans; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Tertiary Care Centers; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Female; Fluconazole; Humans; Immunocompetence; Lung; Lung Diseases, Fungal; Tomography, X-Ray Computed; Young Adult

A rare case of 70-year-old woman with adult T-cell leukemia/lymphoma who developed multifocal choroiditis from a dissemination of Cryptococcus neoformans is reported. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. Sequential optical coherence tomographic images disclosed the involvement of the choroid and the consecutive changes in its architecture during the course of treatment. The recognition of these ocular manifestations may be important for the rapid diagnosis of C. nerformans-disseminated diseases. Rapid diagnosis and prompt therapy with intravitreal injection as well as systemic fosfluconazole and liposomal amphotericin B led to clinical improvement of intraocular cryptococcosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Cryptococcus neoformans; Eye; Eye Infections, Fungal; Fatal Outcome; Female; Fluconazole; Humans; Intravitreal Injections; Leukemia-Lymphoma, Adult T-Cell; Multifocal Choroiditis; Organophosphates; Tomography, Optical Coherence

Cryptococcosis by Cryptococcus gattii occurs mainly in immunocompetent hosts, however, during the last decades, a growing number of cases in immunocompromised individuals have been noticed around the world. This report presents epidemiological, clinical and outcome aspects of patients with cryptococcosis caused by this species from a non-endemic area in Brazil. Of 278 Cryptococcus spp. clinical isolates recovered during the same period, 267 (96%) were molecularly identified as Cryptococcus neoformans VNI genotype and 11 (4%) as C. gattii VGII genotype by URA-5 RFLP. Of the 11 C. gattii patients, eight were male, mean age of 47.5 years. Of these, four were HIV-infected, one was kidney transplanted, one presented low CD4

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Brazil; Cryptococcosis; Cryptococcus gattii; DNA, Fungal; Female; Fluconazole; Genotype; Humans; Invasive Fungal Infections; Male; Meningitis; Middle Aged; Polymorphism, Restriction Fragment Length; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult

Early diagnosis, efficient clinical support, and proper antifungal therapy are essential to reduce death and sequels caused by cryptococcosis. The emergence of resistance to the antifungal drugs commonly used for cryptococcosis treatment is an important issue of concern. Thus, the in vitro antifungal susceptibility of clinical strains from northern Brazil, including C. neoformans VNI (n = 62) and C. gattii VGII (n = 37), to amphotericin B (AMB), 5-flucytosine, fluconazole, voriconazole, and itraconazole was evaluated using the Etest and Vitek 2 systems and the standardized broth microdilution (CLSI-BMD) methodology. According to the CLSI-BMD, the most active in vitro azole was voriconazole (C. neoformans VNI modal MIC of 0.06 μg/ml and C. gattii VGII modal MIC of 0.25 μg/ml), and fluconazole was the least active (modal MIC of 4 μg/ml for both fungi). Modal MICs for amphotericin B were 1 μg/ml for both fungi. In general, good essential agreement (EA) values were observed between the methods. However, AMB presented the lowest EA between CLSI-BMD and Etest for C. neoformans VNI and C. gattii VGII (1.6% and 2.56%, respectively, P < .05 for both). Considering the proposed Cryptococcus spp. epidemiological cutoff values, more than 97% of the studied isolates were categorized as wild-type for the azoles. However, the high frequency of C. neoformans VNI isolates in the population described here that displayed non-wild-type susceptibility to AMB is noteworthy. Epidemiological surveillance of the antifungal resistance of cryptococcal strains is relevant due to the potential burden and the high lethality of cryptococcal meningitis in the Amazon region.

Topics: Amphotericin B; Antifungal Agents; Brazil; Clinical Laboratory Techniques; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Disk Diffusion Antimicrobial Tests; Drug Resistance, Fungal; Flucytosine; Humans; Microbial Sensitivity Tests; Voriconazole

Fungal central nervous system (CNS) infections show a high mortality rate and only a few antifungal agents are available to treat these infections. We hypothesize that the different biochemical properties of human cerebrospinal fluid (CSF) compared to the standard growth medium lead to the altered activity of antifungal agents in CSF. We investigated the in vitro activity of two of these agents, i.e., amphotericin B (AmB) and voriconazole (VOR), against three different fungi in CSF in comparison to sabouraud-dextrose broth (SDB).. CSF samples from patients who did not receive any antibiotics were collected. Time-kill curves were performed in CSF and SDB using static antibiotic concentrations of AmB and VOR against ATCC strains of Candida albicans, Candida krusei, and Cryptococcus neoformans.. In our experiments, both AmB and VOR showed superior activity in SDB compared to CSF. Nevertheless, AmB achieved fungicidal activity in CSF after 24 h against all test strains. Voriconazole only achieved fungistatic activity against C. albicans and C. neoformans in CSF.. In summary, our data demonstrate that growth of fungal pathogens but even more importantly activity of antifungal agents against Candida and Cryptococcus species can differ significantly in CSF compared to the standard growth medium. Both findings should be taken into consideration when applying PK/PD simulations to fungal infections of the CNS.

Topics: Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Central Nervous System Infections; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Humans; Voriconazole

Cryptococcus species are an encapsulated fungal pathogen that cause cryptococcal meningitis. There are limited therapeutic options for this infection. The management includes the use of different antifungals such as amphotericin B, flucytosine, or fluconazole, either alone or in combination. However, numerous therapeutic failures, as well as the limited effectiveness of such therapeutics, have been described. Diphenyl diselenide is a chemically synthesised molecule with was found to have antimicrobial activity. In this study, we evaluated the antifungal activities of fluconazole, amphotericin B and flucytosine, in combination with diphenyl diselenide against 30 clinical isolates of Cryptococcus spp. using CLSI M27-A3 method and the checkerboard microdilution technique. Our results show that the combination of flucytosine and diphenyl diselenide displayed 100% of synergism. However, when we analysed (PhSe)

Topics: Amphotericin B; Antifungal Agents; Benzene Derivatives; Cryptococcosis; Cryptococcus; Drug Synergism; Fluconazole; Flucytosine; Humans; Microbial Sensitivity Tests; Organoselenium Compounds

Cryptococcosis is a common opportunistic infection in patients infected by Human Immunodeficiency Virus (HIV) and is the second leading cause of mortality in Acquired Immunodeficiency Syndrome (AIDS) patients worldwide. The most frequent presentation of cryptococcal infection is subacute meningitis, especially in patients with a CD4+ T Lymphocytes count below 100 cells/μL. However, in severely immunosuppressed individuals Cryptococcus neoformans can infect virtually any human organ, including the bone marrow, which is a rare presentation of cryptococcosis.. A 45-year-old HIV-infected male patient with a CD4+ T lymphocyte count of 26 cells/μL who presented to the emergency department with fever and pancytopenia. Throughout the diagnostic evaluation, the bone marrow aspirate culture yielded encapsulated yeasts in budding, identified as Cryptococcus sp. The bone marrow biopsy revealed a hypocellularity for age and absence of fibrosis. It was observed presence of loosely formed granuloma composed of multinucleated giant cells encompassing rounded yeast like organisms stained with mucicarmine, compatible with Cryptococcus sp. Then, the patient underwent a lumbar puncture to investigate meningitis, although he had no neurological symptoms and neurological examination was normal. The cerebrospinal fluid culture yielded Cryptococcus sp. The species and genotype identification step showed the infection was caused by Cryptococcus neoformans var. grubii (genotype VNI). The patient was initially treated with amphotericin B deoxycholate plus fluconazole for disseminated cryptococcosis, according to guideline recommendations. However, the patient developed acute kidney injury and the treatment was switched for fluconazole monotherapy. The symptoms disappeared completely with recovery of white blood cells and platelets counts. Cerebrospinal fluid cultures for fungi at one and two-weeks of treatment were negative.. Bone marrow infection caused by Cryptococcus neoformans is a rare presentation of cryptococcosis. The cryptococcal infection should be included for differential diagnosis in HIV-infected patients with fever and cytopenias, especially when CD4+ T lymphocytes count is below 100 cells/μL.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Fluconazole; Genotype; HIV Infections; Humans; Male; Meningitis; Middle Aged

The case was a 29-year-old male with no previous history of serious disease. He developed headache and fever, which then worsened and he was admitted to our hospital. His temperature was 38.3°C and he had a stiff neck. In cerebrospinal fluid (CSF) tests, the opening pressure was high, the cell count was increased, and the CSF/serum glucose ratio was decreased. In addition, he was positive for cryptococcal antigen. According to these findings, he was diagnosed with cryptococcal meningoencephalitis and antifungal treatment was initiated. His symptoms then improved, but on day 18 after admission, he developed convulsions, and on day 28, right visual field defects appeared. Brain MRI showed disseminated lesions in the bilateral cerebral cortex. Despite a decrease of the cryptococcal antigenic value in the CSF, the IgG index was elevated. IL-6, 8 and 10 in CSF were high levels on Day 1, then gradually reduced as the symptoms improved. But on Day 28, worsening of symptoms, IL-10 was significantly increased dispite IL-6 and 8 reducing. Therefore, the exacerbation of his symptoms and expansion of the lesions were not caused by the Cryptococcus itself, and it was considered that they were due to the late deterioration of cryptococcosis, which responded to steroid treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Antigens, Fungal; Biomarkers; Cryptococcosis; Cryptococcus neoformans; Disease Progression; Humans; Immunocompetence; Immunoglobulin G; Magnetic Resonance Imaging; Male; Meningoencephalitis; Methylprednisolone; Neuroimaging; Pulse Therapy, Drug; Treatment Outcome; Voriconazole

A 51-year-old man with a medical history of coronary artery disease and dyslipidaemia presented with acute myocardial infarction resulting in cardiogenic shock, necessitating intra-aortic balloon pump placement and extracorporeal membrane oxygenation (ECMO). His hospital course was complicated by several infectious complications including ECMO circuit

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Ciprofloxacin; Cryptococcosis; Cryptococcus neoformans; Extracorporeal Membrane Oxygenation; Fluconazole; Flucytosine; Heart-Assist Devices; Humans; Immunocompetence; Intra-Aortic Balloon Pumping; Male; Middle Aged; Shock, Septic; ST Elevation Myocardial Infarction

Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Combined Modality Therapy; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Female; Fluconazole; Humans; Kidney Transplantation; Lung Diseases, Fungal; Radiography, Thoracic; Treatment Outcome; Voriconazole; Young Adult

Approximately 180,000 people worldwide die from cryptococcosis each year, probably due to the ineffectiveness and toxicity of drugs currently available to treat the disease. Amphotericin B (AMB) is effective for killing the fungus, but has serious adverse effects linked to excessive production of reactive oxygen species which compromise renal function. Pioglitazone (PIO) is a peroxisome proliferator-activated receptor-γ agonist widely repositioned as an adjuvant of various drugs that have toxic effects due to its antioxidant and anti-inflammatory effects. This study evaluated PIO in combination with AMB for the treatment of cryptococcosis. PIO was found to reduce serum creatinine and glutamic-oxalacetic transaminase levels in mice treated with PIO+AMB. In vitro, PIO was able to control harmful oxidative bursts induced by AMB without compromising the antifungal effect. In vivo, PIO+AMB increased the survival rate compared with AMB alone, and improved the morbidity of the animals. PIO+AMB was more efficient than AMB alone for inhibiting fungal transmigration from the lungs to the brain, and killing yeasts that reached the central nervous system, avoiding the establishment of meningoencephalitis. In a phagocytosis assay, PIO did not influence the engulfment and fungicidal activity of macrophages induced by AMB, but reduced the oxidative bursts after the reduction of fungal burden, pointing to control of the pathogen without leading to excessive stress which can be damaging to the host. In conclusion, PIO+AMB was found to ameliorate cryptococcosis in a murine model, indicating that it is a promising therapeutic adjuvant for combating and controlling this fungal infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Antioxidants; Cryptococcosis; Cryptococcus gattii; Disease Models, Animal; Drug Repositioning; Drug Therapy, Combination; Mice, Inbred C57BL; Pioglitazone; Survival Analysis; Treatment Outcome

Even though it is widely known that Cryptococcus spp. may transmit cryptococcosis trough aerosol formed when dried birds (mainly pigeons) droppings are dispersed and become airborne, little is known about the role of these birds in harboring other pathogenic yeasts in their gastrointestinal tract, feathers and beaks, specifically because these animals often stay and reproduce close or even above air conditioner units. Here we evaluated the prevalence of pathogenic yeasts isolated from pigeon droppings collected in the outside area of a University Hospital in Brazil. We also aimed to investigate the pathogenic potential and antifungal susceptibility of Candida species of medical interest isolated from these samples. Therefore, we performed the evaluation of virulence factors attributes expression in vitro, including the ability to adhere to human buccal epithelial cells and biofilm formation and to produce lytic enzymes, such as phospholipases, proteinases and hemolysins. Antifungal susceptibility testing against fluconazole, itraconazole, amphotericin and micafungin was also performed. The Candida genus was the most prevalent in our study, with several medically important species being isolated. Of note, these strains were able to express several virulence factors in vitro, clearly showing their pathogenic potential. Our study was able to demonstrate that Candida spp. isolated from pigeon droppings may express virulence factors in the same manner of clinical isolates, suggesting a pathogenic potential for these yeasts. The fact these strains were collected from the outside area of a tertiary hospital may be of interest, because they may be a source of infection, specifically to immunocompromised hosts.

Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Brazil; Candida; Columbidae; Cryptococcosis; Drug Resistance, Fungal; Feces; Fluconazole; Itraconazole; Microbial Sensitivity Tests; Virulence Factors

In the search for new antifungal agents, a novel series of fifteen hydrazine-thiazole derivatives was synthesized and assayed in vitro against six clinically important Candida and Cryptococcus species and Paracoccidioides brasiliensis. Eight compounds showed promising antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.45 to 31.2 μM, some of them being equally or more active than the drug fluconazole and amphotericin B. Active compounds were additionally tested for toxicity against human embryonic kidney (HEK-293) cells and none of them exhibited significant cytotoxicity, indicating high selectivity. Molecular modeling studies results corroborated experimental SAR results, suggesting their use in the design of new antifungal agents.

Topics: Antifungal Agents; Candida; Candidiasis; Cryptococcosis; Cryptococcus; HEK293 Cells; Humans; Microbial Sensitivity Tests; Models, Molecular; Paracoccidioides; Paracoccidioidomycosis; Structure-Activity Relationship; Thiazoles

Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.

Topics: Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fungal Proteins; HEK293 Cells; Hep G2 Cells; Humans; IMP Dehydrogenase; Models, Molecular; Oxadiazoles; Thiophenes

Infections occur more frequently in patients receiving biologics. However, cryptococcal infection is uncommon in patients receiving tocilizumab, an interleukin-6 inhibitor, in contrast to patients receiving tumor necrosis factor-α inhibitors. In this report, we describe a case of disseminated cryptococcosis in a 55-year-old man who was receiving tocilizumab every 2 weeks along with daily prednisolone and cyclosporine for Castleman's disease. He initially developed cellulitis on both upper limbs, and his condition worsened despite antibacterial therapy. Chest X-ray scanning and computed tomography demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was detected in blood, skin, and sputum cultures. He was diagnosed with disseminated cryptococcosis, and successfully treated with liposomal amphotericin B for a week followed by oral fluconazole for 11 months. The findings of this study indicate that cryptococcosis should be considered during the differential diagnosis of infection in patients receiving tocilizumab, especially in the presence of other risk factors for infections or a short tocilizumab dosing interval.

Topics: Amphotericin B; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antifungal Agents; Castleman Disease; Cryptococcosis; Cryptococcus neoformans; Cyclosporine; Fluconazole; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisolone; Risk Factors

The aim of this study was to assess the biotope of the Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast, and clarify the possible epidemiological relationship between environmental and clinical strains.. Samples from Eucalyptus camaldulensis (n=136), Mangifera indica (n=13) and pigeon droppings (n=518) were collected from different sites close to the living environment of Ivorian HIV patients with cryptococcosis (n=10, 50 clinical strains). Clinical and environmental strains were characterized by molecular serotyping and genotyping [RFLP analysis of the URA5 gene, (GACA)4, (GTG)5 and M13 PCR fingerprinting] and compared.Results/Key findings. Environmental strains were recovered only from the pigeon droppings. In vitro susceptibility profiles showed that all strains were susceptible to fluconazole, flucytosine and amphotericin B. All environmental strains consisted of C. neoformans (A, AFLP1/VNI), whereas clinical strains included C. neoformans (A, AFLP1/VNI), C. neoformans x Cryptococcus deneoformans hybrids (AD, AFLP3/VNIII) and Cryptococcus deuterogattii (B, AFLP6/VGII). Two patients were co-infected with both C. neoformans and C. neoformans x C. deneoformans hybrids. We noticed a low genetic diversity among the environmental samples compared to the high diversity of the clinical samples. Some clinical strains were genetically more similar to environmental strains than to other clinical strains, including those from the same patient.. These results provide new information on the ecology and epidemiology of the C. neoformans/C. gattii species complex in Ivory Coast.

Topics: Adult; Amphotericin B; Antifungal Agents; Chloramphenicol; Cote d'Ivoire; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; DNA, Fungal; Environmental Microbiology; Female; Fluconazole; Flucytosine; Genotype; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Mycological Typing Techniques; Prospective Studies; Serotyping; Young Adult

Cryptococcosis is a subacute or chronic disease. For many years, amphotericin B has been used in severe fungal infections. Voriconazole is a triazole with high bioavailability, a large distribution volume, and excellent penetration of the central nervous system (CNS). The objective of this study was to evaluate the production of pro-inflammatory cytokines in the lungs during an experimental infection caused by C. neoformans in murine model (SCID) that was treated with amphotericin B and voriconazole. After intravenous inoculation with 3.0×10

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Inflammation; Lung; Lung Diseases, Fungal; Mice; Severe Combined Immunodeficiency; Voriconazole

Cryptococcosis is a fungal disease of global significance for which new effective treatments are needed. The conjugation of the synthetic antimicrobial peptide fragment UBI 31-38 to a coumarin derivative showed to be an effective approach for the design of a novel anticryptococcal agent. In addition to antifungal activity, the conjugate exhibited intense fluorescence, which could be valuable for mechanistic investigations of this molecule. In this work, we studied the photophysical properties of the conjugate and confocal scanning laser microscopy was used to inspect the distribution of the peptide-coumarin conjugate in Cryptococcus cell. The synergism of this compound with amphotericin B or fluconazole against C. gattii and C. neoformans strains was also investigated. The results indicated that the fluorescent conjugate alone as well as its combination with amphotericin B are promising tools against cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Coumarins; Cryptococcosis; Cryptococcus; Dose-Response Relationship, Drug; Drug Synergism; Humans; Microbial Sensitivity Tests; Molecular Structure; Peptide Fragments; Photochemical Processes; Structure-Activity Relationship

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Cryptococcus gattii; Drug Therapy, Combination; Eye Diseases; Eye Infections, Fungal; Fluconazole; Flucytosine; HIV Infections; Humans; Infusions, Intravenous; Male; Meningitis, Cryptococcal; Retinitis; Tomography, Optical Coherence; Vitreous Body

Topics: Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Ilium; Immunocompetence; Lung Diseases, Fungal; Middle Aged; Osteomyelitis; Positron Emission Tomography Computed Tomography; Treatment Outcome

Cryptococcus neoformans is one of the most lethal fungi causing mortality across the globe. Immuno-competent patients and patients taking immuno-suppressive medications are extremely susceptible to its infection. For effective removal of cryptococcal burden, there is an urgent need for new forms of therapy. In the present study, we have explored the potential effects of amphotericin B (AMB) and fluconazole (FLC) in combination, against cryptococcosis in Swiss albino mice. To enhance the therapeutic potential of the tested drugs, they were entrapped into fibrin microspheres; a dual delivery vehicle comprising of poly-lactide co-glycolide (PLGA) microsphere that was additionally encapsulated into the fibrin cross-linked plasma bead. Dynamics of fibrin microspheres included survival and fungal burden in lung, liver and spleen of treated mice. While each drug was effective in combination or alone, prominent additive potential of AMB and FLC were clearly observed when used in fibrin microsphere. Significant reduction in fungal burden and increase in survival rate of AMB + FLC-fibrin microspheres treated mice shows an extensive accessibility of both tested drugs without any side-effects. A full potential of two-drug combination encapsulated in fibrin microspheres proposes an effective approach of safe delivery to the target site in their intact form and decrease the drug associated toxicities.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Synergism; Fluconazole; Lactic Acid; Male; Mice; Microbial Sensitivity Tests; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer

Cryptococcosis is the second most common cause of invasive fungal infections in renal transplant recipients in many countries, and data on graft outcome after treatment for this infection is lacking in less-resourced health care settings.. Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss, and mortality rates were evaluated. Predictors of mortality and graft loss were estimated.. A total of 38 (97.4%) patients treated with amphotericin B deoxycholate (AMBd) showed graft dysfunction after antifungal initiation and 8 (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels, and graft dysfunction concomitant to AMBd therapy and an additional nephrotoxic condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high CSF opening pressure, positive CSF India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with AMBd and an additional nephrotoxic condition and graft loss within 30 days.. Graft dysfunction was common in renal transplant recipients with cryptococcosis treated with AMBd. The rate of graft loss rate was high, most frequently in patients with concomitant nephrotoxic conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population requiring a polyene induction regimen for treatment of severe cryptococcosis in all health care systems caring for transplantation recipients.

Topics: Adult; Aged; Allografts; Amphotericin B; Antifungal Agents; Brazil; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Female; Graft Rejection; Humans; Invasive Fungal Infections; Kidney; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Transplant Recipients; Young Adult

Topics: Amphotericin B; Antifungal Agents; Apoptosis; Biofilms; Cell Membrane; Cell Membrane Permeability; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; DNA Fragmentation; Ergosterol; Fungal Capsules; Humans; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Opportunistic Infections; Phosphorylcholine; Plankton; Reactive Oxygen Species

Gastrointestinal (GI) cryptococcosis is rarely reported. Most cases were diagnosed during evaluation of comorbid conditions, incidental findings, or postmortem. Here, we present a case of Crohn's disease with gastrointestinal cryptococcosis that resembled exacerbation of Crohn's disease.. A 64-year-old woman with Crohn's disease (CD) was referred to Siriraj Hospital due to worsening of abdominal pain and watery diarrhea for 2 weeks. The dose of immunosuppressive agents was increased for presumed exacerbation of CD. Pathologic examination of tissue obtained from polypoid mass at ileocecal valve and multiple clean-based ulcers at cecum revealed active ileitis and colitis with multiple round shape organisms with capsule, which was compatible with Cryptococcus species. Disseminated cryptococcosis was diagnosed due to gastrointestinal involvement and presumed pulmonary involvement regarding the presence of an oval-shaped cavitary lesion on chest X-ray and computed tomography of the lung. Patient was successfully treated with amphotericin B followed by fluconazole with satisfactory result.. Early diagnosis of gastrointestinal cryptococcosis in Crohn's disease is difficult due to the lack of specific symptoms and sign or mimicking an exacerbation of Crohn's disease. Seeking for other site of involvement in disseminated cryptococcosis including lung or central nervous system as well as detection of serum cryptococcal antigen would be helpful for early diagnosis and management.

Topics: Amphotericin B; Antifungal Agents; Crohn Disease; Cryptococcosis; Disease Progression; Female; Fluconazole; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Invasive Fungal Infections; Middle Aged; Tomography, X-Ray Computed

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 spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i.e., fluconazole (FLC), and amphotericin B (AMB). Therefore, in vivo studies are necessary to test the above hypothesis. In this study, the efficacy of FLC and AMB at controlling C. gattii infection was evaluated in a murine model of cryptococcosis caused by C. gattii. The infected mice were treated with FLC + AMB combinations and showed a significant improvement in survival as well as reduced morbidity, reduced lung fungal burden, and the absence of yeast in the brain when FLC was used at higher doses, according to the Tukey test and principal component analysis. Altogether, these results indicate that combinatorial optimization of antifungal therapy can be an option for effective control of cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus gattii; Disease Models, Animal; Drug Therapy, Combination; Fluconazole; Humans; Lung; Mice; Microbial Sensitivity Tests; Treatment Outcome

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

Cryptococcosis is an opportunistic fungal infection whose etiology is. Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status.. Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated.. Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died.. The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst.. La Criptococosis es una infección micótica oportunista cuya etiología es el complejo. Paciente masculino de 65 años, procedente de un área rural con exposición crónica a aves de corral, sin antecedentes patológicos, con cuadro clínico inicial consistente en cefalea crónica, fiebre, convulsiones y alteración del estado mental.. Al principio sin signos de hipertensión intracraneana ni meníngeos y examen neurológico normal, con posterior desarrollo de ataxia, disdiadococinesia y dismetría. Se diagnosticó Cerebelitis Criptocococica con ayuda de repetidos estudios de LCR y resonancia magnética nuclear.. Se inició terapia antifúngica con Anfotericina B y Fluconazol, con respuesta tórpida y el paciente fallece.. La Cerebelitis Criptocococica es una presentación clínica infrecuente que requiere sospecha clínica y recursos diagnósticos para definir el tratamiento de forma temprana. La inmunosupresión no es requisito para padecer esta infección.

Topics: Aged; Amphotericin B; Antifungal Agents; Cerebellar Diseases; Cryptococcosis; Fatal Outcome; Fluconazole; Humans; Magnetic Resonance Spectroscopy; Male

Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this genus that in recent decades have increasingly caused opportunistic infections in humans, mainly in immunocompromised patients; the best therapy for such infection being unknown. Using a murine model of systemic infection by these fungi, we have evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally, at 25 mg/kg and the combination of AMB plus VRC against three C. albidus and two C. laurentii strains. All the treatments significantly reduced the fungal burden in all the organs studied. The combination showed a synergistic effect in the reduction in fungal load, working better than both monotherapies. The histopathological study confirmed the efficacy of the treatments.

Topics: Administration, Intravenous; Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Fluconazole; Immunocompromised Host; Lung; Mice; Microbial Sensitivity Tests; Spleen; Voriconazole

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Debridement; Dermatomycoses; Female; Flucytosine; Humans

T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo .. The MICs for 15 clinical isolates were determined according to CLSI guidelines and time-kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2 h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection.. The MIC range, MIC 50 , MIC 90 and geometric mean MIC of T-2307 were 0.0078-0.0625, 0.0313, 0.0625 and 0.0394 mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2 mg/kg/day, amphotericin B at 1 mg/kg/day and fluconazole at 160 mg/kg/day from 2 h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1 mg/kg/day.. T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.

Topics: Amidines; Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Disease Models, Animal; Drug Discovery; Drug Resistance, Fungal; Fluconazole; Humans; Lung; Lung Diseases, Fungal; Mice; Microbial Sensitivity Tests; Voriconazole

Heat-shock proteins (Hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role in the infectious process. This study investigated the effect of pharmacological inhibition of Hsp90 by radicicol on the Cryptococcus neoformans/Cryptococcus gattii species complex--agents of the most common life-threatening fungal infection amongst immunocompromised patients. The influence of Hsp90 inhibition was investigated regarding in vitro susceptibility to antifungal agents of planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production of virulence factors in vitro, and experimental infection in Caenorhabditis elegans. Hsp90 inhibition inhibited the in vitro growth of planktonic cells of Cryptococcus spp. at concentrations ranging from 0.5 to 2 μg ml(-1) and increased the in vitro inhibitory effect of azoles, especially fluconazole (FLC) (P < 0.05). Inhibition of Hsp90 also increased the antifungal activity of azoles against biofilm formation and mature biofilms of Cryptococcus spp., notably for Cryptococcus gattii. Furthermore, Hsp90 inhibition compromised the permeability of the cell membrane, and reduced planktonic growth at 37 °C and the capsular size of Cryptococcus spp. In addition, Hsp90 inhibition enhanced the antifungal activity of FLC during experimental infection using Caenorhabditis elegans. Therefore, our results indicate that Hsp90 inhibition can be an important strategy in the development of new antifungal drugs.

Topics: Amphotericin B; Animals; Antifungal Agents; Biofilms; Caenorhabditis elegans; Cell Membrane; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Ergosterol; Fluconazole; HSP90 Heat-Shock Proteins; Humans; Itraconazole; Melanins; Microbial Sensitivity Tests; Plankton; Voriconazole

Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml(-1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Argentina; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Epidemiologic Methods; Fluconazole; Flucytosine; HIV Infections; Humans; Itraconazole; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Triazoles; Voriconazole

Opportunistic infections have been reported infrequently in primary HIV infection. We report a case of cryptococcemia in primary HIV infection. To our knowledge there has not been such a case reported. Our case highlights the need for clinicians to be wary of other opportunistic infections, including cryptococcosis, in primary HIV infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diabetes Mellitus; Fluconazole; Hepatitis B; HIV Infections; Humans; Liver Function Tests; Male; Syphilis; Treatment Outcome

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Cryptococcus; Deoxycholic Acid; Drug Combinations; Female; Genotype; Humans; Male; Virulence Factors

Cryptococcosis is a potentially severe infection that usually occurs in a setting of immunosuppression. Its occurrence outside of this context is rare. We report a case of disseminated cryptococcosis revealed by a spectacular skin disease in an immunocompetent patient.. A 40-year-old male patient had been presenting multiple nodules and tumors on his face for one month in a context of asthenia and intermittent fever. Histological examination of a skin biopsy revealed encapsulated yeasts strongly suggestive of Cryptococcus neoformans. Mycological examination of the skin biopsy and cerebrospinal fluid isolated Cryptococcus gattii. The blood cultures were positive. Brain MRI demonstrated cryptococcal parenchymal involvement. Screening for primary or secondary immunodeficiency was negative. The patient received amphotericin B 1mg/kg/day and fluconazole 600mg/day but died 2months after diagnosis.. Cryptococcosis is a potentially severe infection caused by C. neoformans. This rare condition occurs most commonly in patients with profound deficiency in terms of cellular immunity. Although rare, the occurrence of cryptococcosis in immunocompetent patients is possible, and in this event the signs are highly polymorphic, which usually makes it very difficult to diagnose. The diagnosis of cryptococcosis is based on the identification by direct examination and after staining with India ink of encapsulated yeasts of the Cryptococcus genus. Culture on Sabouraud medium is essential for identification of the species. Treatment for disseminated cryptococcosis involves amphotericin B, often associated with flucytosine IV. In the event of meningitis infection in non-HIV patients, mortality continues to be around 15%, despite adequate medical treatment.. Although rare, cryptococcosis can occur in immunocompetent subjects. The prognosis is severe even after treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Facial Dermatoses; Fatal Outcome; Fluconazole; Fungemia; Humans; Immunocompetence; Male; Meningitis, Cryptococcal

Cryptococcus neoformans and Cryptococcus gattii are the main causative agents of cryptococcosis, a systemic fungal disease that affects internal organs and skin, and which is acquired by inhalation of spores or encapsulated yeasts. It is currently known that the C. neoformans/C. gattii species complex has a worldwide distribution, however, some molecular types seem to prevail in certain regions. Few environmental studies of Cryptococcus have been conducted in the Brazilian Amazon. This is the first ecological study of the pathogenic fungi C. neoformans/C. gattii species complex in the urban area of Manaus, Amazonas, Brazil. A total of 506 samples from pigeon droppings (n = 191), captive bird droppings (n = 60) and tree hollows (n = 255) were collected from June 2012 to January 2014 at schools and public buildings, squares, pet shops, households, the zoo and the bus station. Samples were plated on niger seed agar (NSA) medium supplemented with chloramphenicol and incubated at 25°C for 5 days. Dark-brown colonies were isolated and tested for thermotolerance at 37°C, cycloheximide resistance and growth on canavanine-glycine-bromothymol blue agar. Molecular typing was done by PCR-RFLP. Susceptibility to the antifungal drugs amphotericin B, fluconazole, itraconazole and ketoconazole was tested using Etest(®) strips. In total, 13 positive samples were obtained: one tree hollow (C. gattiiVGII), nine pigeon droppings (C. neoformansVNI) and three captive bird droppings (C. neoformansVNI). The environmental cryptococcal isolates found in this study were of the same molecular types as those responsible for infections in Manaus.

Topics: Amphotericin B; Animals; Antifungal Agents; Birds; Brazil; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Disease Reservoirs; Environmental Microbiology; Feces; Fluconazole; Humans; Itraconazole; Ketoconazole; Molecular Typing; Mycological Typing Techniques; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Trees

Topics: Amphotericin B; Anti-Infective Agents; Costs and Cost Analysis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Health Expenditures; Humans

Cryptococcosis is mainly caused by members of the Cryptococcus gattii/Cryptococcus neoformans species complexes. Here, we report the molecular characterisation and in vitro antifungal susceptibility of Danish clinical cryptococcal isolates. Species, genotype, serotype and mating type were determined by amplified fragment length polymorphism (AFLP) fingerprinting and qPCR. EUCAST E.Def 7.2 MICs were determined for amphotericin B, flucytosine, fluconazole, voriconazole and isavuconazole. Most isolates were C. neoformans (serotype A; n = 66) and belonged to genotype AFLP1/VNI (n = 61) or AFLP1B/VNII (n = 5) followed by Cryptococcus deneoformans (serotype D; genotype AFLP2, n = 20), C. neoformans × C. deneoformans hybrids (serotype AD; genotype AFLP3, n = 13) and Cryptococcus curvatus (n = 2). Six isolates were C. gattii sensu lato, and one isolate was a C. deneoformans × C. gattii hybrid (genotype AFLP8). All isolates were amphotericin B susceptible. Flucytosine susceptibility was uniform MIC50 of 4-8 mg l(-1) except for C. curvatus (MICs >32 mg l(-1) ). Cryptococcus gattii sensu lato isolates were somewhat less susceptible to the azoles. MICs of fluconazole (>32 mg l(-1) ), voriconazole (≥0.5 mg l(-1) ) and isavuconazole (0.06 and 0.25 mg l(-1) respectively) were elevated compared to the wild-type population for 1/19 C. deneoformans and 1/2 C. curvatus isolates. Flucytosine MIC was elevated for 1/61 C. neoformans (>32 mg l(-1) ). Antifungal susceptibility revealed species-specific differential susceptibility, but suggested acquired resistance was an infrequent phenomenon.

Topics: Amphotericin B; Antifungal Agents; Azoles; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Denmark; DNA, Fungal; Drug Resistance, Fungal; Fluconazole; Genotype; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Serotyping

The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB). Drug interaction chequerboard assay evaluated: AMB + 5FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii (VGII) and C. neoformans isolates were found to belong to genotype VNI (n = 62) and VNII (n = 4). C. neoformans VNII was significantly less susceptible than VNI (P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ (P < 0.0001). C. deuterogattii was less susceptible than C. neoformans VNI for FCZ (P = 0.0170), ITZ (P < 0.0001) and TRB (P = 0.0090). The combination FCZ + TRB showed 95.16% of synergistic effect against C. neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5FC.

Topics: Amphotericin B; Antifungal Agents; Brazil; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Drug Combinations; Drug Synergism; Fluconazole; Flucytosine; Genotype; Humans; Itraconazole; Microbial Sensitivity Tests; Molecular Typing; Naphthalenes; Polymorphism, Restriction Fragment Length; Terbinafine; Voriconazole

The emergence of fluconazole-resistant Cryptococcus gattii is a global concern, since this azole is the main antifungal used worldwide to treat patients with cryptococcosis. Although pharmacokinetic (PK) and pharmacodynamic (PD) indices are useful predictive factors for therapeutic outcomes, there is a scarcity of data regarding PK/PD analysis of antifungals in cryptococcosis caused by resistant strains. In this study, PK/PD parameters were determined in a murine model of cryptococcosis caused by resistant C. gattii. We developed and validated a suitable liquid chromatography-electrospray ionization tandem mass spectrometry method for PK studies of fluconazole in the serum, lungs, and brain of uninfected mice. Mice were infected with susceptible or resistant C. gattii, and the effects of different doses of fluconazole on the pulmonary and central nervous system fungal burden were determined. The peak levels in the serum, lungs, and brain were achieved within 0.5h. The AUC/MIC index (area under the curve/minimum inhibitory concentration) was associated with the outcome of anti-cryptococcal therapy. Interestingly, the maximum concentration of fluconazole in the brain was lower than the MIC for both strains. In addition, the treatment of mice infected with the resistant strain was ineffective even when high doses of fluconazole were used or when amphotericin B was tested, confirming the cross-resistance between these drugs. Altogether, our novel data provide the correlation of PK/PD parameters with antifungal therapy during cryptococcosis caused by resistant C. gattii.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Chromatography, Liquid; Colony Count, Microbial; Cryptococcosis; Cryptococcus gattii; Disease Models, Animal; Drug Resistance, Fungal; Fluconazole; Lung; Male; Mice, Inbred C57BL; Microbial Sensitivity Tests; Models, Biological; Spectrometry, Mass, Electrospray Ionization

The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspirin; Cell Death; Cell Line; Cryptococcosis; Cryptococcus; Drug Repositioning; Drug Resistance, Fungal; Fluconazole; Ibuprofen; Mice; RAW 264.7 Cells

Cryptococcal meningitis is a severe opportunistic infection in HIV-infected patients. In Ivory Coast, despite the availability of antiretroviral treatment (ART), this infection is still prevalent. The study investigates the genetic diversity of 363 clinical isolates of Cryptococcus from 61 Ivorian HIV-positive patients, the occurrence of mixed infections and the in vitro antifungal susceptibility of the isolates. Serotyping was performed via LAC1 and CAP64 gene amplification. Genotyping was performed using the phage M13 core (GACA)

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cote d'Ivoire; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Female; Genetic Variation; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Mycological Typing Techniques; Polymorphism, Restriction Fragment Length; Prospective Studies; Young Adult

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Fluconazole; HIV Infections; Humans

Cryptococcus neoformans is an important opportunistic pathogen that causes serious mortality and morbidity in AIDS patients. Although its incidence has decreased with proper antiretroviral treatment (ART), it is still a major concern in areas with low socioeconomic HIV endemic countries with poor sources of therapy. In our country, pediatric HIV infection and so, HIV-related opportunistic infections are very rare. In order to pay attention to this unusual collaboration; herein, we presented a pediatric case who was diagnosed with HIV and disseminated cryptococcus infection concomitantly. A 6.5-year-old previously healthy girl has admitted to our hospital with the complaints of prolonged fever, cough and hemoptysis. On her physical examination she had oral candidiasis, generalized lymphadenopathy and hepatosplenomegaly. Laboratory findings were as follows; white blood cell count: 3170 µL (neutrophil: 2720 µL, lymphocyte: 366 µL), hemoglobin level: 7.8 gr/dl, hematocrit: 25.5% platelets: 170.000 µL, CRP: 15.2 mg/L and serum IgG level: 1865 mg/dl. Her anti-HIV test yielde,d positive result and confirmed by Western blot assay, together with a high viral load (HIV-RNA: 3.442.000 copies/ml). She was started ART (lamivudine, zidovudine and lopinavir/ritonavir combination) with the diagnosis of stage 3 HIV infection (AIDS). Posteroanterior chest radiograph showed mediastinal extension and nodular parenchyma. Since the patient was suspected to have pulmonary tuberculosis based on the clinical and radiological findings, empirical antituberculosis therapy was started. Because of the insistance of fever, three different blood specimens, bone marrow and gastric aspirates were collected for culture, in which all of them yielded C.neoformans growth. She was then diagnosed as disseminated cryptococcosis and treated with liposomal amphotericin B and fluconazole successfully. Although pediatric HIV infection is usually diagnosed secondary to maternal disease, it can rarely be presented later in life with opportunistic infections. In the case of unusual infectious diseases, in addition to primary immune deficiency syndromes, HIV infection should also be kept in mind. Herein, we discussed a pediatric case with two rare infectious agents reported in our country and wanted to focus on secondary immune deficiency related with pediatric HIV infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Child; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; Humans; Tuberculosis, Pulmonary

Cryptococcus neoformans is a common fungus found throughout the environment that causes opportunistic disease in immunocompromised individuals. Infection of humans with C neoformans usually manifests as lung disease through inhalation of spores or meningoencephalitis by involvement of the central nervous system. Rarely, dissemination in the form of cutaneous lesions can occur in individuals with long term immunosuppression. We present a patient with C. neoformans manifesting as cellulitis with focal segmental glomerulosclerosis treated with corticosteroids. Because of the mortality associated with disseminated cryptococcosis, early identification, especially of atypical cutaneous presentations is critical from a dermatological perspective.

Topics: Amphotericin B; Antifungal Agents; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Cyclosporine; Fluconazole; Flucytosine; Fungemia; Glomerulosclerosis, Focal Segmental; Humans; Immunocompromised Host; Immunosuppressive Agents; Leg Dermatoses; Male; Middle Aged; Prednisone; Skin

We report a case of pulmonary cryptococcoma, in an adult with recently detected diabetes, mimicking as lung cancer. A 45-year-old gentleman with past history of pulmonary tuberculosis presented with fever, cough with expectoration, pleuritic chest pain and hemoptysis. Chest radiograph and computed tomography revealed right lower lobe mass which significantly enhanced on contrast administration. Ultrasound guided biopsy was done which on histopathological examination showed non-necrotizing granulomas with narrow-based budding yeast cells suggestive of cryptococcosis. Detailed work-up for dissemination of infection was negative. A dramatic response to anti-fungal treatment was observed and the patient is doing fine on follow-up.

Topics: Amphotericin B; Antifungal Agents; Chest Pain; Cough; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Hemoptysis; Humans; Lung Diseases, Fungal; Male; Middle Aged; Tomography, X-Ray Computed; Treatment Outcome

Cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. Combination of antifungal substances is a promising way to increase the percentage of successful treatment. Pedalitin (PED) is a natural substance obtained from Pterogyne nitens. The aim of this study was to verify the efficacy of PED alone and in combination with amphotericin B (AmB) in vitro and in vivo against Cryptococcus spp. In the in vitro assay, minimum inhibitory concentrations (MICs) of 0.125 mg/L for AmB and 3.9 mg/L for PED were found when the substances were tested alone, whilst in the combination treatment the active concentration of both decreased, with MICs of 0.03 mg/L for AmB and 1 mg/L for PED. In the survival assay, fungal burden study and histopathological assays it was possible to study the efficacy of the substances alone and in combination. The efficacy of combination therapy was considered better than monotherapy as evaluated in a Galleria mellonella model and a murine model. Thus, the combination of PED and AmB is an interesting alternative for anticryptococcal fungal treatment. Moreover, a correlation was observed between the invertebrate and murine models for this antifungal treatment combination.

Topics: Amphotericin B; Animals; Antifungal Agents; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Synergism; Flavones; Lepidoptera; Mice, Inbred BALB C; Microbial Sensitivity Tests; Survival Analysis; Treatment Outcome

We report 7 HIV-infected children with cryptococcosis. Median age and CD4 counts were 9.3 years and 12 cells/mm, respectively. Two children died early. Of 4 children requiring prolonged amphotericin B and fluconazole at a dosage above 12 mg/kg/d, 3 presented with meningitis and 1 with fever. Immune reconstitution inflammatory syndrome contributed to morbidity through exacerbations at the primary site and elsewhere.

Topics: Adolescent; Age Distribution; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Child; Cryptococcosis; Female; Fluconazole; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Retrospective Studies

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

The incidences of infection with Mycobacterium tuberculosis and Cryptococcus neoformans in immunocompromised patients have increased, but there are few documented cases of their coexistence. We present the case of a 9-year-old female with systemic lupus erythematosus (SLE), treated with prednisone and cyclophosphamide, who was admitted to the emergency department with a 2-week history of fever, headache, malaise, fatigue, and diplopia 3 years after diagnosis. Physical examination showed limitation of abduction of the right eye, Kernig and Brudzinski signs, and hyporeflexia. Magnetic resonance imaging showed hyperdense lesions located in the caudate nucleus, and lumbar puncture showed pleocytosis, a low glucose level, and increased protein level. Cerebrospinal fluid culture identified C. neoformans and PCR detect M. tuberculosis. Treatment was started with isoniazid, rifampin, pyrazinamide, ethambutol, and amphotericin B. We found two similar reports in adults, but no data were found for either pediatric or SLE patients.

Topics: Amphotericin B; Antitubercular Agents; Child; Coinfection; Cryptococcosis; Cryptococcus neoformans; Ethambutol; Female; Humans; Immunocompromised Host; Isoniazid; Lupus Erythematosus, Systemic; Meningoencephalitis; Mycobacterium tuberculosis; Pyrazinamide; Rifampin

Topics: Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cryptococcosis; Cryptococcus; Fluconazole; Hodgkin Disease; Humans; Male

Topics: Amphotericin B; Animals; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood-Brain Barrier; Cryptococcosis; Male; Verapamil

Topics: Amphotericin B; Animals; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood-Brain Barrier; Cryptococcosis; Male; Verapamil

Infections due to Cryptococcus neoformans cause severe disease, mostly in AIDS patients. The antifungal drug recommended for the initial treatment of these infections is amphotericin B with or without flucytosine, but treatment failure occurs, associated with high mortality. Thus, antifungal susceptibility testing is needed. However, the in vitro susceptibility tests available for C. neoformans are not useful to detect isolates that are not susceptible to antifungal agents such as amphotericin B. The aims of the present study were: (1) to determine and compare the in vitro activity of amphotericin B against C. neoformans clinical isolates by using different dilution and diffusion methods; (2) to evaluate the concordance among the methods used and the reference method; (3) to evaluate which method could be the best to correlate with the clinical outcome. The reference method EDef 7.2 from the European Committee on Antimicrobial Susceptibility Testing and commercial Etest strips were used to determine the minimal inhibitory concentration against amphotericin B. curves, minimal fungicidal concentration, and a disk diffusion method were also developed to evaluate the cidal activity of amphotericin B. The time-kill curve assay showed correlation (p < 0.05) with clinical outcome, whereas EDef 7.2, minimal fungicidal concentration, Etest, and disk diffusion showed no correlation (p > 0.05). Thus, the time-kill curve assay could be a potential tool to guide a more efficient treatment when amphotericin B is used.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Female; Humans; Male; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Cryptococcus arboriformis (C. arboriformis) is a novel Cryptococcus species belonging to the genus Trichosporonales. This novel species was identified definitively in 2007 using D1/D2 26S ribosomal DNA gene sequencing. In this article, we present a rare case of central line-associated bloodstream infection caused by C. arboriformis with successful treatment of this infection.

Topics: Aged; Amphotericin B; Antifungal Agents; Catheter-Related Infections; Catheterization, Central Venous; Cryptococcosis; Cryptococcus; DNA, Fungal; Female; Humans; Phylogeny; RNA, Ribosomal; Shock, Septic; Treatment Outcome

Cryptococcus albidus keratitis is a rare and difficult diagnosed disease. Here we report a case of C albidus keratitis early diagnosed by dot hybridization assay and successfully treated with intrastromal injection of Amphotericin B (AB).A 45-year-old man presented with left red eye for 2 days. The slit lamp examination exhibited deep corneal infiltrations. Smears and cultures were performed but revealed negative findings. Molecular detection of pathogens was performed by dot hybridization assay, and C albidus keratitis was diagnosed. Despite the identification of C albidus, the clinical condition still worsened due to deep corneal infiltration. After performing intrastromal injection of AB, the corneal infiltration gradually improved.C albidus is a rare cause of diseases in humans and should be considered as a potential pathogen of corneal ulcer. The prognosis of C albidus keratitis will improve if the condition is recognized early and treated properly.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Early Diagnosis; Humans; Keratitis; Male; Middle Aged

This study evaluated the synergistic interactions between amphotericin B (AMB) and azithromycin (AZM), daptomycin (DAP), linezolid (LNZ), minocycline (MINO), fluconazole (FLZ), flucytosine (5FC), linezolid (LZD), or tigecycline (TIG) against clinical isolates of Cryptococcus neoformans var. grubii before and after capsule induction. High synergism (>75%) was observed for the combinations, AMB+5FC, AMB+TIG, AMB+AZM, AMB+LZD and AMB+MINO but only in the strains after capsule induction. The results show that the presence of the capsule may lower the minimum inhibitory concentrations (MICs) of antifungal agents, but antimicrobial activity can be improved by combining antifungal and antibacterial agents.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Interactions; Fungal Capsules; Humans; Microbial Sensitivity Tests

We present a case of a 59-year-old woman with Chagas disease who received a kidney transplant. At month 44 post-transplantation, the patient presented with diarrhea that had persisted for 2 months. Colonoscopy showed a colon ulcer and differential diagnoses included cytomegalovirus, bacteria, or parasite infection; drug-related diarrhea; Crohn's disease; celiac disease; and malignancy. The ulcer tissue was positive for Cryptococcus neoformans. Successful treatment consisted of amphotericin B for 8 days and oral fluconazole (800 mg daily) for 3 months. This case illustrates that a colonic ulcer, although rare, could be cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Colonic Diseases; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Female; Fluconazole; Humans; Kidney Transplantation; Middle Aged; Ulcer

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Osteomyelitis; Positron-Emission Tomography

The polyene antifungal agent Amphotericin B exhibits potent and broad spectrum fungicidal activity. However, high nephrotoxicity can hinder its administration in resource poor settings. Quantification of early fungicidal activity in studies of HIV patients with cryptococcosis demonstrate that 5-Fluorocytosine therapy in combination with Amphotericin B results in faster clearance than with Amphotericin B alone. In vitro synergy between the two drugs has also been reported but the mechanism by which 5-Fluorocytosine synergizes with Amphotericin B has not been delineated. In this study we set out to investigate the effect of genetic mutation or pharmacologic repression of de novo pyrimidine and purine biosynthesis pathways on the Amphotericin B susceptibility of Cryptococcus neoformans. We demonstrate that a ura- derivative of wild type Cryptococcus neoformans strain H99 is hypersensitive to Amphotericin B. This sensitivity is remediated by re-introduction of a wild type URA5 gene, but not by addition of exogenous uracil to supplement the auxotrophy. Repression of guanine biosynthesis by treatment with the inosine monophosphate dehydrogenase inhibitor, mycophenolic acid, was synergistic with Amphotericin B as determined by checkerboard analysis. As in Cryptococcus neoformans, a ura(-) derivative of Candida albicans was also hypersensitive to Amphotericin B, and treatment of Candida albicans with mycophenolic acid was likewise synergistic with Amphotericin B. In contrast, neither mycophenolic acid nor 5-FC had an effect on the Amphotericin B susceptibility of Aspergillus fumigatus. These studies suggest that pharmacological targeting of nucleotide biosynthesis pathways has potential to lower the effective dose of Amphotericin B for both C. neoformans and C. albicans. Given the requirement of nucleotide and nucleotide sugars for growth and pathogenesis of Cryptococcus neoformans, disrupting nucleotide metabolic pathways might thus be an effective mechanism for the development of novel antifungal drugs.

Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Cryptococcosis; Cryptococcus neoformans; Flucytosine; HIV Infections; Humans; Microbial Sensitivity Tests; Mycophenolic Acid; Nucleotides

Use of the PLEX-ID system can lead to a rapid molecular diagnosis in microbiology. To illustrate the clinical implications of this new diagnostic tool, we present the case of a 46-year-old patient admitted with severe respiratory failure and septic shock. Cryptococcal pneumonia was diagnosed by Fungi-Fluor™ staining of the bronchoalveolar lavage (BAL) and the patient tested positive for HIV. Unfortunately, he died 12h after admission despite intensive care support and treatment with broad-spectrum antibiotics, amphotericin B, and flucytosine. Retrospective use of the PLEX-ID on the BAL, bronchial aspirate, and blood yielded Cryptococcus neoformans in all fluids tested. Rapid molecular diagnosis with PLEX-ID, especially when performed on the blood of septic patients, may reduce the time to adequate treatment and limit the number of diagnostic procedures needed.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coinfection; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Female; Flucytosine; HIV Infections; Humans; Male; Middle Aged; Nucleic Acid Amplification Techniques; Pneumonia

A 50-year-old man, who had received an ABO-incompatible living related preemptive renal transplantation 1 year before, presented with painful lesions on both lower extremities and fever. At first, bacterial cellulitis was suspected and antibiotic therapy was initiated, but it was not effective. The serum cryptococcal antigen titer was 1:4,098, and pathologic examination of debrided tissue and wound pus culture revealed cryptococcal necrotizing fasciitis. Liposomal amphotericin B and fluconazole were started, and repeated debridement and skin grafting were performed. Because his graft function deteriorated because of antibody-mediated rejection and polyoma viral nephropathy, hemodialysis was induced on day 9 of hospitalization. During the treatment, he suffered repeated urinary tract infections, which were treated with antibiotics, and cytomegalovirus retinopathy, which was treated with ganciclovir. His cryptococcal necrotizing fasciitis was successfully cured by the combination of antimicrobial treatment and surgical procedures. He could walk with a cane and was discharged on day 298 of hospitalization. Cryptococcal necrotizing fasciitis in renal transplant recipients is so rare that only 14 cases have been reported. The mortality is not very high, but the prognosis of the patient is complicated by worsening of the cryptococcal infection of the central nervous system (CNS). Early detection and treatment to prevent spreading to other sites, especially the CNS or disseminated disease, is very important in cases of cryptococcal necrotizing fasciitis.

Topics: Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Fasciitis, Necrotizing; Fluconazole; Humans; Kidney Transplantation; Male; Middle Aged

Topics: Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Lung Diseases, Fungal

Topics: Amphotericin B; Antifungal Agents; Biomarkers; Child; Cough; Cryptococcosis; Fever; Fluconazole; Humans; Lung; Lung Diseases, Fungal; Male; Radiography, Thoracic; Tomography, X-Ray Computed

Cryptococcosis is a potentially lethal opportunistic infection among human immunodeficiency virus (HIV)-infected individuals. The mortality rate of patient with cryptococcal meningoencephalitis (CM) in Thailand is high. Studying the factors associated with treatment failure is important to improve outcome.. A retrospective study of patients with cryptococcosis in Siriraj Hospital, Thailand, during 2005-2008 was conducted. Treatment options, outcomes, survival and factors associated with outcomes and mortality were analyzed.. A total of 143 patients with cryptococcosis were enrolled. Mean age was 39 years old and 58.7% were male. There were 124 HIV-infected patients (86.7%) and 116 of those had CM. Favorable clinical response in HIV-associated CM was 55.2% and 6-month survival was 67.2%. Relapse was found in 21 patients (18.1%). Factors associated with favorable clinical response included lower opening and closing pressures and a higher white blood cell in cerebrospinal fluid (CSF). Favorable mycological response was 56.8% and factors associated with favorable mycological response were a lower CD4+ T-lymphocyte count and a longer amphotericin B treatment. The median time to achieve CSF sterilization was 30 days. Factors associated with survival were a longer course of amphotericin B, a lower CSF opening pressure and a higher white blood cell in CSF.. High mortality rate of HIV-associated CM was demonstrated and most likely linked to inadequate induction antifungal therapy resulting in inability to sterilize CSF. New strategies and/or guidelines are suggested to improve survival.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Humans; Male; Meningitis, Cryptococcal; Meningoencephalitis; Middle Aged; Retrospective Studies; Thailand; Treatment Outcome

Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in vitro was significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected with Cryptococcus neoformans. In uninfected mice, the brain/plasma ratios of AMB were increased 15 min (3.5 versus 2.0; P < 0.05) and 30 min (5.2 versus 2.8; P < 0.05) after administration of verapamil or 45 min (6.0 versus 3.9; P < 0.05) and 60 min (5.4 versus 3.8; P < 0.05) after itraconazole administration. The increases in brain/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (P < 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.

Topics: Amphotericin B; Animals; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Blood-Brain Barrier; Cerebral Cortex; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Drug Therapy, Combination; Injections, Intraventricular; Itraconazole; Male; Mice; Survival Analysis; Verapamil

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; DNA, Ribosomal; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Phylogeny; Saccharomyces cerevisiae; Sequence Homology, Nucleic Acid

Amphotericin B (AMB) is an antifungal drug that binds to ergosterol and forms pores at the cell membrane, causing the loss of ions. In addition, AMB induces the accumulation of reactive oxygen species (ROS), and although these molecules have multiple deleterious effects on fungal cells, their specific role in the action mechanism of AMB remains unknown. In this work, we studied the role of ROS in the action mechanism of AMB. We determined the intracellular induction of ROS in 44 isolates of different pathogenic yeast species (Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida krusei, Cryptococcus neoformans, and Cryptococcus gattii). We also characterized the production of ROS in AMB-resistant isolates. We found that AMB induces the formation of ROS in all the species tested. The inhibition of the mitochondrial respiratory chain by rotenone blocked the induction of ROS by AMB and provided protection from the killing action of the antifungal. Moreover, this phenomenon was absent in strains that displayed resistance to AMB. These strains showed an alteration in the respiration rate and mitochondrial membrane potential and also had higher catalase activity than that of the AMB-susceptible strains. Consistently, AMB failed to induce protein carbonylation in the resistant strains. Our data demonstrate that the production of ROS by AMB is a universal and important action mechanism that is correlated with the fungicidal effect and might explain the low rate of resistance to the molecule. Finally, these data provide an opportunity to design new strategies to improve the efficacy of this antifungal.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catalase; Cell Membrane; Cryptococcosis; Cryptococcus; Drug Resistance, Fungal; Electron Transport; Ergosterol; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Oxidative Stress; Oxygen Consumption; Reactive Oxygen Species; Rotenone; Uncoupling Agents

Topics: Amphotericin B; Antifungal Agents; Biopsy; Child; Cryptococcosis; Dermatomycoses; Drug Therapy, Combination; Fluconazole; Humans; Kidney Transplantation; Male; Skin; Time Factors; Transplant Recipients; Treatment Outcome

We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to amphotericin B, fluconazole, flucytosine, and voriconazole using broth microdilution (BMD) according to the Clinical and Laboratory Standards Institute M27-A3 document and compared these results with Etest and Vitek 2(®). Essential agreement (EA) of Etest and Vitek 2(®) compared to BMD was determined. Low MICs that were below the epidemiological cutoff values of the 4 antifungal agents tested were demonstrated by all isolates. The EA of Etests for fluconazole, amphotericin, and voriconazole was 95.1%, 83.3%, and 91.2%, respectively, and for Vitek 2(®) EA for fluconazole, amphotericin, and flucytosine was 97.1%, 95.1%, and 97.1%, respectively. The Vitek 2(®) showed good agreement with BMD and is a suitable alternative. Etests demonstrated good EA for azoles only. Clinical cryptococcal isolates from Durban remain susceptible to current recommended antifungal therapy.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Disk Diffusion Antimicrobial Tests; Fluconazole; Flucytosine; Humans; South Africa; Voriconazole

To illustrate three different ophthalmic presentations of cryptococcal meningitis (CM).. CM is the most common manifestation of extra-pulmonary cryptococcosis. Intracranial hypertension occurs in up to 75% of patients with CM and is associated with increased mortality. CM can present to the ophthalmologist as vision loss, papilledema, abducens palsy, and/or other cranial neuropathies.. We report three cases, two C. neoformans and one C. gattii, highlighting the various CM presentations. The first was a woman immunosuppressed following kidney transplantation in whom idiopathic intracranial hypertension (IIH) was initially suspected. The second was a man immunocompromised by previously undiagnosed HIV/AIDS who presented with signs and symptoms of increased intracranial pressure. The third case is an immunocompetent man with bilateral disc edema and an incomplete macular star diagnosed with presumed neuroretinitis. Further evaluation revealed positive CSF cryptococcal antigen with culture positive for C. gattii.. Ophthalmologists should be aware that cryptococcosis can mimic more benign etiologies including IIH and neuroretinitis. Additionally, C. gattii, an emerging organism, can infect immunocompetent patients. In contrast to the typical treatment of increased ICP, serial lumbar punctures are recommended while acetazolamide and surgical CSF shunting may be harmful.

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Antigens, Fungal; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Therapy, Combination; Eye Infections, Fungal; Female; Flucytosine; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Meningitis, Cryptococcal; Optic Neuritis; Papilledema

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus; Dog Diseases; Dogs; Fatal Outcome; Fluconazole; Male

Cryptococcosis due to Cryptococcus gattii is endemic in various parts of the world, affecting mostly immunocompetent patients. A national surveillance study of cryptococcosis, including demographical, clinical and microbiological data, has been ongoing since 1997 in Colombia, to provide insights into the epidemiology of this mycosis.. From 1,209 surveys analyzed between 1997-2011, 45 cases caused by C. gattii were reported (prevalence 3.7%; annual incidence 0.07 cases/million inhabitants/year). Norte de Santander had the highest incidence (0.81 cases/million/year), representing 33.3% of all cases. The male: female ratio was 3.3∶1. Mean age at diagnosis was 41±16 years. No specific risk factors were identified in 91.1% of patients. HIV infection was reported in 6.7% of patients, autoimmune disease and steroids use in 2.2%. Clinical features included headache (80.5%), nausea/vomiting (56.1%) and neurological derangements (48.8%). Chest radiographs were taken in 21 (46.7%) cases, with abnormal findings in 7 (33.3%). Cranial CT scans were obtained in 15 (33.3%) cases, with abnormalities detected in 10 (66.7%). Treatment was well documented in 30 cases, with most receiving amphotericin B. Direct sample examination was positive in 97.7% cases. Antigen detection was positive for all CSF specimens and for 75% of serum samples. C. gattii was recovered from CSF (93.3%) and respiratory specimens (6.6%). Serotype was determined in 42 isolates; 36 isolates were serotype B (85.7%), while 6 were C (14.3%). The breakdowns of molecular types were VGII (55.6%), VGIII (31.1%) and VGI (13.3%). Among 44 strains, 16 MLST sequence types (ST) were identified, 11 of them newly reported.. The results of this passive surveillance study demonstrate that cryptococcosis caused by C. gattii has a low prevalence in Colombia, with the exception of Norte de Santander. The predominance of molecular type VGII is of concern considering its association with high virulence and the potential to evolve into outbreaks.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Colombia; Cryptococcosis; Cryptococcus gattii; Female; Humans; Incidence; Male; Middle Aged; Multilocus Sequence Typing; Prevalence; Retrospective Studies; Risk Factors; Virulence; Young Adult

A young man presented with a history of cough, chest pain and streaky haemoptysis with low-grade fever. Further evaluation revealed a mass in the left hemithorax, which was biopsied to reveal cryptococcoma. The patient was HIV negative. Flow cytometry lymphocyte subset analysis showed reduced CD4+ T lymphocytes. Absolute CD4+ lymphocyte count was only 230 (normal range 530-1300). The patient was started on injectable amphotericin B, which was given for 1 month, and he was discharged on oral fluconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Chest Pain; Cough; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Hemoptysis; Humans; Lung Diseases, Fungal; Male

A 58-year-old man presented with right chest pain, anorexia, general malaise, and fever. Chest computed tomography showed a mass lesion with right middle lobe atelectasis. The bronchoscopy showed polypoid lesions with a smooth surface in each right middle lobe bronchial lumen. The histopathology revealed the dense accumulation of histiocyte-like cells with foamy cytoplasm under the bronchial epithelium along with yeast-like fungi stained positively with both Alcian blue and Grocott's stains. Cryptococcus neoformans was cultured from the bronchial washings. We diagnosed the patient with pulmonary cryptococcosis with endobronchial lesions. The fluconazole treatment was changed to liposomal amphotericin-B and flucytosine after the diagnosis of cryptococcal meningitis. The minimum inhibitory concentration of the fungi suggested resistance to fluconazole and flucytosine. The lesion regressed after these treatments.

Topics: Amphotericin B; Animals; Bronchi; Bronchoscopy; Columbidae; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Lung; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome

Miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. To further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. In vitro testing of these compounds against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Aspergillus fumigatus, and Cryptococcus neoformans revealed that N-benzyl-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3a), N,N-dimethyl-N-(4-nitrobenzyl)-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3d), and N-(4-methoxybenzyl)-N,N-dimethyl-2-{[(hexadecyloxy)hydroxyphosphinyl]oxy}ethanaminium inner salt (3e) exhibited minimum inhibitory concentrations (MIC) of 2.5-5.0 μg/mL against all tested pathogens, when compared to miltefosine with MICs of 2.5-3.3 μg/mL. Compound 3a showed low in vitro cytotoxicity against three mammalian cell lines similar to miltefosine. In vivo testing of 3a and miltefosine against C. albicans in a mouse model of systemic infection did not demonstrate efficacy. The results of this study indicate that further investigation will be required to determine the potential usefulness of the alkylphosphocholines in the treatment of invasive fungal infections.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candida; Candidiasis; Cell Line; Cryptococcosis; Cryptococcus neoformans; Fungi; Humans; Mice; Mycoses; Phosphorylcholine

The goal of this study was to determine the degree to which the persistence of cryptococcosis, overall 1-year mortality, and 1-year mortality due to cryptococcosis were influenced by initial antifungal treatment regimen in a cohort of adults with cryptococcosis treated at a tertiary care medical center. Risk factors, underlying conditions, treatment, and mortality information were obtained for 204 adults with cryptococcosis from Duke University Medical Center (DUMC) from 1996 to 2009. Adjusted risk ratios (RR) for persistence and hazard ratios (HR) for mortality were estimated for each exposure. The all-cause mortality rate among patients with nonsevere disease (20%) was similar to that in the group with disease (26%). However, the rate of cryptococcosis-attributable mortality with nonsevere disease (5%) was much lower than with severe disease (20%). Flucytosine exposure was associated with a lower overall mortality rate (HR, 0.4; 95% confidence interval [CI], 0.2 to 0.9) and attributable mortality rate (HR, 0.5; 95% CI, 0.2 to 1.2). Receiving a nonrecommended antifungal regimen was associated with a higher relative risk of persistent infection at 4 weeks (RR, 1.9; 95% CI, 0.9 to 4.3), and the rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher than that of those receiving recommended dosing (HR, 2.3; 95% CI, 1.0 to 5.0). Thus, the 2010 Infectious Diseases Society of America (IDSA) guidelines are supported by this retrospective review as a best-practice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between all-cause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Administration Schedule; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Incidence; Male; Practice Guidelines as Topic; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome

We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months.. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined.. Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema.. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.

Topics: Adult; Amphotericin B; Antifungal Agents; Australia; Cryptococcosis; Cryptococcus gattii; Female; Fluconazole; Flucytosine; Follow-Up Studies; Humans; Male; Time Factors; Treatment Outcome

Topics: Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Bone Marrow; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Female; Humans; Latex Fixation Tests; Liver; Urinalysis; Urine

Cryptococcus gattii is responsible for an expanding epidemic of serious infections in Western Canada and the Northwestern United States (Pacific Northwest). Some patients with these infections respond poorly to azole antifungals, and high azole MICs have been reported in Pacific Northwest C. gattii. In this study, multiple azoles (but not amphotericin B) had higher MICs for 25 Pacific Northwest C. gattii than for 34 non-Pacific Northwest C. gattii or 20 Cryptococcus neoformans strains. We therefore examined the roles in azole resistance of overexpression of or mutations in the gene (ERG11) encoding the azole target enzyme. ERG11/ACT1 mRNA ratios were higher in C. gattii than in C. neoformans, but these ratios did not differ in Pacific Northwest and non-Pacific Northwest C. gattii strains, nor did they correlate with fluconazole MICs within any group. Three Pacific Northwest C. gattii strains with low azole MICs and 2 with high azole MICs had deduced Erg11p sequences that differed at one or more positions from that of the fully sequenced Pacific Northwest C. gattii strain R265. However, the azole MICs for conditional Saccharomyces cerevisiae erg11 mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. We conclude that neither ERG11 overexpression nor variations in ERG11 coding sequences was responsible for the high azole MICs observed for the Pacific Northwest C. gattii strains we studied.

Topics: Amphotericin B; Antifungal Agents; Canada; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Fungal Proteins; Gene Expression; Genetic Complementation Test; Humans; Microbial Sensitivity Tests; Mutation; Northwestern United States; Saccharomyces cerevisiae; Sterol 14-Demethylase

Topics: Adult; Amphotericin B; Antifungal Agents; Apgar Score; Brain; Cryptococcosis; Female; Fluconazole; Humans; Immunocompetence; Infant, Newborn; Intracranial Hypertension; Magnetic Resonance Imaging; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome

Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fluconazole; Meningitis, Cryptococcal; Meningoencephalitis; Mice; Microbial Sensitivity Tests; Phosphorylcholine; Survival

The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole-trimethoprim (SMX/TMP) and sulfadiazine-pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of C. neoformans and C. gattii. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of C. neoformans (n = 15) and C. gattii (n = 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of Cryptococcus spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in C. neoformans and C. gattii planktonic cells. Our results highlight the antifungal potential of antifolate drugs.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Combinations; Environmental Microbiology; Folic Acid Antagonists; Humans; Microbial Sensitivity Tests; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Cellulitis is an unusual presentation of cryptococcal infection in renal allograft recipients. In such patients, disseminated cryptococcal infection can result in significant morbidity and mortality. Patients are often treated with antibiotics before a definitive diagnosis is made, delaying appropriate therapy. We describe the case of a 43-year-old post renal transplant recipient presenting with fever and swelling in the right thigh. On physical examination, the patient was found to have features suggestive of cellulitis with minimal slurring of speech. Material obtained from incision and drainage of the wound showed yeast cells resembling Cryptococcus spp. Blood culture and cerebrospinal fluid culture were also found to have growth of Cryptococcus neoformans. He received treatment with amphotericin B 6 mg/kg daily intravenously for two weeks, then continued with fluconazole 400 mg daily for three months. The patient showed a remarkable improvement. There was no recurrence of cryptococcosis after four months of follow-up. The diagnosis of disseminated cryptococcosis should be considered in differential diagnosis of cellulitis among non HIV immunocompromised hosts. A high clinical suspicion and early initiation of therapy is needed to recognize and treat patients effectively.

Topics: Adult; Amphotericin B; Antifungal Agents; Cellulitis; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Diagnosis, Differential; Fluconazole; Humans; Immunocompromised Host; Kidney Transplantation; Male; Treatment Outcome

Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with AIDS (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5 μg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC ≤ 4 μg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 μg/mL and 0.396 μg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC ≤ 8 μg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC ≤ 0.25 μg/mL). The geometric mean MIC of fluconazole stood at 15.14 μg/mL and of itraconazole was 0.144 μg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Cross Infection; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Multiple, Fungal; Fluconazole; Flucytosine; Fungemia; Humans; Itraconazole; Kidney Transplantation; Lymphoma; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Postoperative Complications; Serbia

We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coinfection; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Microscopy; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010.. To analyze the data obtained during this period.. Retrospective analysis of the corresponding surveys.. A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 106 inhabitants while in AIDS patients this rate rose to 3.3 x 103. In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%.. Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Child; Colombia; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance, Multiple, Fungal; Female; Fluconazole; Health Surveys; Humans; Incidence; Male; Middle Aged; Population Surveillance; Retrospective Studies; Symptom Assessment; Young Adult

Cryptococcosis is an important systemic mycosis caused by members of the Cryptococcus neoformans species complex. This disease is potentially fatal in various animals, including koalas. We describe the long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization of koalas by Cryptococcus neoformans and C. gattii. Of the 15 animals investigated through the use of samples obtained by nasal swabs, antigen titer measurements, and pathologic examination, C. neoformans was found associated with nine koalas and C. gattii with one animal. Nine koalas showed subclinical disease and one clinical infections and antigenemia. Treatment with fluconazole, itraconazole and amphotericin B upon detection of C. neoformans or C. gattii was not effective. The results of the present study showed that C. neoformans was the predominant species isolated from the nasal swab samples and the fungus might have naturally become associated with the koalas' nasal cavities at Kanazawa Zoological Gardens. The unclear treatment effectiveness might have been caused by a shorter treatment period that is routinely used and unstable itraconazole absorption. This investigation also underscores the need for identifying effective treatment regimens for subclinical cryptococcosis and efficient measures for eradicating C. neoformans and C. gattii in koalas.

Topics: Amphotericin B; Animals; Animals, Zoo; Antifungal Agents; Carrier State; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Female; Fluconazole; Fungemia; Itraconazole; Male; Nasal Cavity; Phascolarctidae; Treatment Outcome

Cryptococcosis is a significant opportunistic mycoses in organ transplant recipients. Topical developments in the field in the past few years have highlighted important issues and at the same time raised new questions regarding the management of this yeast. These include, for example, management of pretransplant cryptococcosis during transplant candidacy and timing of transplant in these instances; potential for donor transmission of cryptococcosis in light of recent fatal transmissions; and prevention and treatment of Cryptococcus-associated immune reconstitution syndrome. Discussed herein are challenges posed by these issues and evidence-based data to optimize the management of posttransplant cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Calcineurin Inhibitors; Cryptococcosis; Evidence-Based Medicine; Humans; Immune Reconstitution Inflammatory Syndrome; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Prevalence; Risk Factors; Transplantation

Cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus Cryptococcus neoformans. The model of systemic cryptococcosis in mice with severe combined immunodeficiency (SCID) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. Amphotericin B, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. Voriconazole is a triazole with high bioavailability, large distribution volume, and excellent penetration of the central nervous system. The objective of this study was to evaluate treatment with amphotericin B (AMB), voriconazole (VRC), and AMB, used in combination with VRC, of experimental pulmonary cryptococcosis in a murine model (SCID). The animals were inoculated intravenously (iv) with a solution containing 3.0 × 10(5) viable cells of C. neoformans ATCC 90112, (serotype A). Treatments were performed with amphotericin B (1.5 mg/kg/day), voriconazole (40.0 mg/kg/day) and AMB (1.5 mg/kg/day) combined with VRC (40.0 mg/kg/day); began 1 day after the initial infection; were daily; and lasted 15 days. Evaluations were performed using analysis of the survival curve and isolation of yeast in the lung tissue. There was a significant increase in survival in groups treated with AMB combined with VRC, compared with the untreated group and groups receiving other treatments (P < 0.05). In the group treated only with VRC and AMB combined with VRC, there was a significant reduction (P < 0.05) in the isolation of C. neoformans in lung tissue. Amphotericin B combined with voriconazole may be an effective alternative to increasing survival and may reduce yeast in the lung tissue of mice with pulmonary cryptococcosis and SCID.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Therapy, Combination; Lung; Lung Diseases, Fungal; Mice; Mice, SCID; Pyrimidines; Severe Combined Immunodeficiency; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fatal Outcome; Fever; Flucytosine; HIV Infections; Humans; Male; Multiple Organ Failure; Respiratory Distress Syndrome

There are few reports concerning the in vitro antifungal susceptibility of clinical and environmental Cryptococcus gattii isolates. In this study, we performed polymerase chain reaction-restriction fragment length polymorphism to investigate the molecular subtypes of 50 clinical and 4 environmental Brazilian isolates of C. gattii and assessed their antifungal susceptibility for fluconazole (FLU) and amphotericin B (Amb) according to recent recommendations proposed for antifungal susceptibility testing of nonfermentative yeasts. Time-kill curve studies were performed using RPMI 1640 medium to analyze the fungicidal effect of AmB. We found 47 VGII (94%) molecular types and 3 VGI (6%) types among the clinical isolates. The environmental isolates were VGII (75%) subtype and VGI (25%) subtype. The FLU-MIC ranged from 1 to 64 mg L(-1), and MIC(50)/MIC(90) values were, respectively, 8/16 mg L(-1). For AmB, the MICs were low and homogeneous, ranging from 0.12 to 0.5 mg L(-1), for VGI or VGII. The time required to reach the fungicidal end point (99.9% killing) was 6 h for the majority of strains (64%), but viable cells of VGII were still present after 48 h of exposition. We pointed out the occurrence of high FLU-MICs for C. gattii isolates with highest values for VGII. Our data also suggest that the rate of killing of C. gattii by AmB is strain dependent, and viable cells of VGII genotype strains were still observed after an extended incubation time, addressing future studies to determine whether the in vitro fungicidal activity could be clinically relevant.

Topics: Amphotericin B; Antifungal Agents; Brazil; Cryptococcosis; Cryptococcus gattii; Drug Resistance, Fungal; Fluconazole; Genotype; Humans; Microbial Sensitivity Tests; Mycological Typing Techniques; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Soil Microbiology; Time Factors

Cryptococcal osteomyelitis is extremely rare and almost always occurs in immunocompromised patients. We describe a case of osteomyelitis due to Cryptococcus neoformans involving both scapula and rib in an immunocompetent and previously healthy patient. The patient received treatment with amphotericin B deoxycholate and flucytosine for 4 weeks, followed by oral fluconazole 400 mg per day for 8 weeks and 200 mg per day for 9 months. The 12-month course of antifungal therapy resulted in complete clinical recovery and undetectable serum cryptococcal antigen. Cryptococcal osteomyelitis should be suspected in any immunocompetent patient with osteolytic lesions on radiological images.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Female; Flucytosine; Humans; Middle Aged; Osteomyelitis; Ribs; Scapula; Time Factors; Treatment Outcome

A human immunodeficiency virus-negative 63-year-old male with autoimmune hemolytic anemia presented with decreased vision, photophobia and hearing loss. After initial testing seemed consistent with sarcoidosis, he was found to have disseminated Cryptococcus with a cryptococcoma of the left eye. Treatment with systemic anti-fungal therapy improved the patient's condition.

Topics: Amphotericin B; Anemia, Hemolytic, Autoimmune; Antifungal Agents; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Eye Infections, Fungal; Fluconazole; Flucytosine; HIV Seronegativity; Humans; Lung Diseases, Fungal; Magnetic Resonance Imaging; Male; Meningitis, Fungal; Middle Aged; Recurrence; Retinal Diseases; Tomography, X-Ray Computed; Vitreous Body

We report the case of a 34-year-old woman with cerebral and pulmonary cryptococcosis. After surgery for uterine cervical cancer, chest CT scan indicated a solitary tumor. Cryptococcosis was detected by transbronchial lung biopsy, and brain MRI showed multiple tumors. We diagnosed the patient with cerebral and pulmonary cryptococcosis. Oral and intravenous antifungal treatments were not effective, and a disturbance of consciousness appeared. We began intraventricular antifungal treatment, and the symptoms improved, with a reduction in the size of multiple lesions. However, the size of the brain lesions increased, and we diagnosed late deterioration of cryptococcosis and corticosteroid response. Because of the refractory clinical course, we examined the Cryptococcus strains from the surgical resected pulmonary lesion and identified Cryptococcus gattii(VG I type). C. gattii occurs predominantly in apparently healthy hosts. An intracranial C. gattii infection is associated with neurological complications and delayed therapeutic response. If cerebral cryptococcosis responds slowly and relatively poorly to antifungal therapy, C. gattii should be considered. Aggressive therapy, including intraventricular therapy and corticosteroids therapy for cryptococcoma, is required.

Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Female; Humans; Lung Diseases, Fungal; Meningitis, Cryptococcal

We compared the epidemiology of laboratory-confirmed paediatric cryptococcal disease with adult-onset disease in the South African population.. The study was an active, prospective, population-based, laboratory-based surveillance in South Africa. We compared cases of paediatric cryptococcosis (<15 years) with cases of adult-onset cryptococcosis that were reported to the surveillance programme between 1 January 2005 and 31 December 2007. The case definition was based on a positive India ink test, cryptococcal antigen test or cryptococcal culture. Clinical case data were obtained at enhanced surveillance sites.. Of 16,192 incident episodes of cryptococcosis in South Africa, 361 (2%) episodes occurred among children. In 2007, incidence was one and 19 cases per 100,000 persons in the general paediatric and adult populations and was 47 and 120 cases per 100,000 persons for HIV-infected children and adults, respectively. Among children, a bimodal peak in incidence was evident in the less than 1-year age group and in the 5 age group. Most children (64%) and adults (63%) were severely immunocompromised (CD4 T-lymphocyte cell count < 50 cells/μl) at the time of diagnosis. On multivariable analysis, children were significantly more likely than adults to be male, diagnosed on blood culture, infected with Cryptococcus gattii, treated with amphotericin B and admitted for a longer stay in hospital.. This series of 361 cases of paediatric cryptococcosis is by far the largest described to date. The diagnosis of cryptococcosis should be considered in the paediatric HIV-infected population, especially among those who are severely immunocompromised.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Age Distribution; Age of Onset; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Cryptococcosis; Cryptococcus gattii; Female; Humans; Immunocompromised Host; Incidence; Infant; Infant, Newborn; Length of Stay; Male; Population Surveillance; Prospective Studies; Sex Distribution; South Africa; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Immunocompetence; Magnetic Resonance Imaging; Male; Osteomyelitis; Sacrum; Treatment Outcome

In the present study, the in vitro susceptibility and capsular width from both melanized and non-melanized Cryptococcus neoformans cells in the presence of Pimenta pseudocaryophyllus crude extract were determined. The results were compared with those obtained for voriconazole and amphotericin B. Melanization was obtained in minimal medium broth with the addition of L-dopa, and the antifungal susceptibility tests were performed using the broth microdilution method. Capsular width of 30 cells of each one of the isolates in medium with crude extracts of P. pseudocaryophyllus or voriconazole or amphotericin B at a concentration corresponding to 0.5 times the minimal inhibitory concentration (MIC) was measured, and the mean was calculated. The MICs and minimal fungicidal concentrations (MFCs) for plant extract and voriconazole were identical for both melanized and non-melanized C. neoformans isolates, but for amphotericin, the MFCs for melanized cells were up to 8 times higher than for non-melanized cells. The capsular width of C. neoformans cells was smaller (p < 0.001) in the presence crude extract of P. pseudocaryophyllus and of voriconazole regardless melanization. The findings of capsule alterations of C. neoformans verified in this study provide fertile ways for future research into the effects of antifungal agents on the pathogenesis of cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Fungal Capsules; Humans; Melanins; Microbial Sensitivity Tests; Pimenta; Plant Extracts; Pyrimidines; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Basal Ganglia; Cryptococcosis; Cryptococcus gattii; Female; Humans; Magnetic Resonance Imaging; Meningoencephalitis; Young Adult

Topics: Abdominal Pain; Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Cerebrospinal Fluid; Constipation; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Headache; Humans; Male; Microscopy; Viral Load

Cryptococcosis is rare among children, only occurring in about 1% of children with HIV. We report the case of a 12-year-old boy with disseminated cryptococcosis. He had a history of recurrent pneumonia. He then developed meningeal symptoms and was found to have disseminated Cryptococcus neoformans by cerebrospinal fluid and bone marrow aspirate culture. He was treated with amphotericin B for 2 weeks (1 mg/kg/day), and then with fluconazole orally for 8 weeks (12 mg/kg/day). He also received a new diagnosis of HIV and was started on antiretroviral therapy 2 weeks after starting antifungal treatment. At follow-up 8 weeks later, he was doing well.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Child; Cryptococcosis; Cryptococcus neoformans; Fluconazole; HIV; HIV Seropositivity; Humans; Male

Nasal masses in the koala (Phascolarctos cinereus) are not uncommon and can be challenging to diagnose and treat. Differential diagnoses for nasal masses in the koala are cryptococcal granulomas, nasal polyps, nasal adenocarcinoma, and osteochondromatosis. This report describes successful surgical approaches for two adult koalas with nasal masses and includes photodocumentation and description of the anatomy of the koala nasal passages from the postmortem transverse sectioning of a normal koala head. Surgical removal of the nasal masses in these koalas resulted in a rapid resolution of clinical signs.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Cryptococcosis; Cryptococcus; Female; Granuloma; Itraconazole; Male; Nose Neoplasms; Phascolarctidae; Skull

A 3-yr-old female koala (Phascolarctos cinereus) was diagnosed with a nasal sinus granuloma caused by Cryptococcus gattii after a pre-shipment examination revealed a latex cryptococcal agglutination titer of 1:512. Successful medical and surgical treatment of the granuloma was monitored using serial latex cryptococcal agglutination titers, serum levels of antifungal drugs, and advanced imaging.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Female; Fluconazole; Granuloma; Itraconazole; Phascolarctidae; Sinusitis

The antifungal spirocyclic guanidine alkaloid, ptilomycalin A, from marine sponge Monanchora arbuscula, inhibits melanogenesis of Cryptococcus neoformans in vitro through inhibition of biosynthesis of laccase in the melanin biosynthetic pathway with an IC(50) of 7.3 μM.

Topics: Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Enzyme Inhibitors; Guanidines; Laccase; Melanins; Porifera

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 × 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Resistance, Fungal; Drug Therapy, Combination; Fluconazole; Lung; Mice; Mice, Inbred BALB C; Mice, SCID; Pyrimidines; Rodent Diseases; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole; Yeasts

An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.

Topics: Abdomen; Amphotericin B; Antifungal Agents; Antigens, Fungal; Brain; Child; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Histocytochemistry; HIV Infections; Humans; Lymphadenitis; Male; Microscopy; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

Topics: Aged; Amphotericin B; Anticoagulants; Antifungal Agents; Cellulitis; Cryptococcosis; Dermatomycoses; Fatal Outcome; Female; Fungemia; Heparin, Low-Molecular-Weight; Hepatitis, Autoimmune; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Cirrhosis; Lung Diseases, Fungal; Necrosis; Prednisone; Radiography; Thrombophilia

The antifungal activity of amphotericin B (AmB) incorporated in three cholesteryl carbonate esters (CCEs), sodium cholesteryl carbonate, cholesteryl palmityl carbonate, and dicholesteryl carbonate, was examined to assess their potential for use in a dry powder aerosol. Formulations containing dissolved AmB were stable for 6 months. The particle size varied inversely with liquid crystalline content with observed mass median aerodynamic diameters ranging from 4 to 8 μ m. This was consistent with the visual appearance of the liquid crystals as being low density and free flowing at room temperature. When dispersed in water, the presence of the CCE reduced the rate and extent of AmB release, consistent with the estimated liquid crystal/water partition coefficient. Nevertheless, the rate of AmB release was always sufficient to kill the fungus as established with bioactivity studies. AmB formulated with CCE as a dry powder appears to be promising for use in treating lung fungal infections.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Carbonates; Cholesterol Esters; Cryptococcosis; Cryptococcus neoformans; Drug Stability; Humans; Particle Size; Solubility

Rituximab-related late-onset neutropenia (R-LON) is an adverse event associated with rituximab. A 65-year-old woman presented with diffuse large B-cell lymphoma of the kidney without bone marrow involvement. She was treated with 4 cycles of CHOP chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisolone at 4-week intervals. Rituximab was also administrated of the second, third, fourth CHOP cycles. She developed a high fever of 38°C, nausea, and severe neutropenia following the four cycles of R-CHOP chemotherapy. Her leukocyte count was 160/μl without neutrophils. Initially, a blood and pleural fluid and cerebrospinal fluid cultures were positive for Cryptococcus neoformans. Once she became asymptomatic following treatment with fluconazole and neutropenia was recovered with lenograstim, she had neck stiffness and admitted soon. Cerebro-spinal fluid (CSF) culture was positive for Cryptococcus neoformans. Treatment with amphotericin B(AMPH-B) and flucytosine(5-FC) was initiated as diagnosis of cryptococcus meningitis. Lenograstim was administrated for 9 months, and amount of dose was 9,750 μg. Cryptococcosis with malignant lymphoma is rare disease, and previously 17 cases were reported. Of note, mortality of disseminated cryptococcosis with malignant lymphoma is 54%. The more and more rituximab is widely used; the cases of severe infection in R-LON may increase.

Topics: Aged; Amphotericin B; Antibodies, Monoclonal, Murine-Derived; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cryptococcosis; Cryptococcus neoformans; Cyclophosphamide; Doxorubicin; Female; Fluconazole; Flucytosine; Humans; Immunologic Factors; Lymphoma, Non-Hodgkin; Neutropenia; Prednisolone; Rituximab; Treatment Outcome; Vincristine

Intensified chemotherapy and hematopoietic stem cell transplantation result in severe and prolonged granulocytopenia with an increased risk of invasive fungal infections. The major fungal species that cause serious infections in cancer patients are Candida species and Aspergillus species. The main features of Candida infection in this context are oropharyngeal candidiasis and Candida esophagitis, chronic disseminated candidiasis, also known as hepatosplenic candidiasis, and candidemia. Aspergillus can cause severe lung infection but also sinusal or CNS infection. Because invasive fungal infections are severe and often life-threatening, preventive and empirical managements have become standard practice. An increasing number of antifungal drugs is now available, notably lipid formulations of amphotericin B (liposomal amphotericin B), new azoles with broad spectrum of activity and echinocandin.

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Azoles; Candidiasis; Child; Cryptococcosis; Echinocandins; Humans; Mycoses; Neoplasms; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Treatment Outcome

Fungal infections of the heart are increasingly described especially in immunocompromised patients. Cardiac involvement can present with myocarditis, pericarditis or endocarditis. Cryptococcal endocarditis is extremely rare, with only four reported cases in the literature. The prognosis, natural history and the optimal management for cryptococcal endocarditis are not well described because of paucity of cases. We report the case of a patient with prosthetic aortic valve endocarditis due to C. neoformans. The diagnosis was confirmed with transthoracic and transesophageal echocardiogram, blood cultures that were positive for C. neoformans and high titers of cryptococcal antigen in the serum. The patient was successfully treated with liposomal amphotericin without surgical intervention.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Echocardiography; Endocarditis; Humans; Male

We conducted a retrospective study of 58 cases of cryptococcosis (1986-2008) with urine test positive for Cryptococcus sp, in Mycology Laboratory, Santa Casa-Hospital Complex, Porto Alegre, RS, Brazil. The diagnosis of cryptococcuria was based on microscopic examination and culture of urinary sediment. Cryptococcus was isolated from other clinical specimens such as blood, cerebrospinal fluid, ascitic and pleural fluids, respiratory secretions, biopsies of skin, nasal and bone marrow. Cryptocccus neoformans was present in 55 cases and Cryptocccus gattii in three cases. Males predominated (79.3%); age ranged from 12 to 86 years. Acquired Immune Deficiency Syndrome (AIDS) were present in 60.3%, 31.1% did not have AIDS and 5.2% were apparently immunocompetent patients. The most frequent signs and symptoms were headache (53.4%) and fever (51.7%). The most widely used medication was the amphotericin B (43 patients). The mortality rate was 45%. We conclude that the mycological examination of the urine can be an alternative simple, non-invasive and useful in diagnosis of disseminated cryptococcosis, especially when used in conjunction with techniques for demonstration of the capsule (nigrosine) and/or production of melanin in special culture media (Staib agar).

Topics: Adolescent; Adult; Agar; Age Distribution; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Child; Cryptococcosis; Cryptococcus; Culture Media; Female; Humans; Male; Microbiological Techniques; Microscopy; Middle Aged; Mycology; Retrospective Studies; Selection, Genetic; Sex Distribution; Urine; Young Adult

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Hepatitis C; Humans; Liver Cirrhosis; Middle Aged; Perineum; Pneumonia; Radiography; Suppuration; Vulva

Topics: Aged; Amphotericin B; Antifungal Agents; British Columbia; Bromhexine; Cryptococcosis; Cryptococcus gattii; Flucytosine; Humans; Lung Diseases, Fungal; Male; Microbial Sensitivity Tests; Radiography; Triazoles

A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. Initially secondary syphilis was suspected. However, RPR was negative. Histopathologic examination revealed a lymphocytic infiltrate with numerous intra-histiocytic fungal organisms. GMS and PAS stains were positive, consistent with the diagnosis of histoplasmosis. We report a case of disseminated histoplasmosis clinically mimicking secondary syphilis.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Diagnosis, Differential; Endemic Diseases; Hepatomegaly; Histoplasmosis; Humans; Itraconazole; Male; Syphilis; Texas

The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecular electrostatic potentials (MEPs) obtained from RHF/6-31G calculations. On the basis of the theoretical predictions three small-size peptides, RQWKKWWQWRR-NH(2), RQIRRWWQWRR-NH(2), and RQIRRWWQW-NH(2) were synthesized and tested. These peptides displayed a significant antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Our experimental and theoretical results allow the identification of a topographical template which can serve as a guide for the design of new compounds with antifungal properties for potential therapeutic applications against these pathogenic fungi.

Topics: Amino Acid Sequence; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Models, Molecular; Mycoses; Peptides; Poecilia; Toxicity Tests, Acute

This study investigated the microbiological characteristics of 100 clinical isolates of Cryptococcus neoformans species complex, including serotypes, mating types, molecular types, antifungal susceptibility and virulence. The isolates were collected at National Taiwan University Hospital from 1999 to 2004. Eight isolates of C. neoformans from pigeon droppings were also evaluated. Among these isolates, 99 were C. neoformans var. grubii serotype A and one was C. neoformans var. gattii serotype B. All of these isolates were alpha mating types. PCR fingerprinting, generated by primers M13 and (GACA)(4), and URA5 gene restriction fragment length polymorphism analysis revealed that C. neoformans var. grubii isolates belonged to the VNI (98 isolates) and the VNII (one isolate) types, and the single C. neoformans var. gattii was VGI type. The similar profiles of clinical and environmental isolates suggest that patients might acquire these yeasts from the environment. The MIC(90) for fluconazole, itraconazole, 5-flucytosine, voriconazole and amphotericin B against all C. neoformans isolates were 8, 0.5, 4, 0.125 and 0.5 mg/L, respectively. All clinical isolates produced urease, phospholipase, capsule and melanin, but these activities varied with individual isolates. Analysis of six clinical and two environmental isolates with various levels of phospholipase activity indicated a correlation between phospholipase activity and the ability to adhere to the lung epithelial cell line, A549. The extent of cell damage, as indicated by lactate dehydrogenase release, also paralleled the phospholipase activity of these isolates. In addition, production of melanin contributed significant protection against amphotericin B killing of the isolates tested.

Topics: Amphotericin B; Antifungal Agents; Azoles; Cryptococcosis; Cryptococcus neoformans; DNA Fingerprinting; DNA, Fungal; Female; Genes, Mating Type, Fungal; Genotype; Humans; Male; Microbial Sensitivity Tests; Mycological Typing Techniques; Random Amplified Polymorphic DNA Technique; Serotyping; Taiwan; Virulence Factors

The export of virulence factors, such as the capsule polysaccharide, to the cell surface is a critical aspect of the pathogenicity of Cryptococcus neoformans. A view of capsule export via exocytosis and extracellular vesicles is emerging, but the molecular mechanisms underlying virulence factor transport pathways remain to be established. In this study, we characterized the APT1 gene, which encodes a predicted integral membrane P-type ATPase belonging to the type IV, Drs2 family of aminophospholipid translocases (flippases) (APTs). APTs maintain the phospholipid asymmetry that is critical in membrane fusion events for trafficking and in establishing cell polarity. Deletion of the APT1 gene resulted in phenotypes consistent with similar roles in C. neoformans. These included altered actin distribution, increased sensitivity to stress conditions (oxidative and nitrosative stress) and to trafficking inhibitors, such as brefeldin A and monensin, a reduction in exported acid phosphatase activity, and hypersensitivity to the antifungal drugs amphotericin B, fluconazole, and cinnamycin. However, there was no difference in growth, capsule size, or melanin production between the wild type and the apt1 mutant strains at either 30 degrees C or 37 degrees C. Despite the absence of an influence on these major virulence factors, Apt1 was required for survival during interactions with macrophages, and apt1 mutants exhibited attenuated virulence in a mouse inhalation model of cryptococcosis. Therefore, Apt1 contributes to virulence and the stress response in C. neoformans through apparent functions in membrane fusion and trafficking that do not influence the deposition of major virulence factors, such as capsule and melanin, outside the cell.

Topics: Actins; Adenosine Triphosphatases; Amphotericin B; Animals; Antifungal Agents; Bacteriocins; Cell Membrane; Cryptococcosis; Cryptococcus neoformans; Endocytosis; Female; Fluconazole; Fungal Proteins; Genetic Complementation Test; Humans; Macrophages; Melanins; Mice; Mice, Inbred BALB C; Oxidative Stress; Peptides, Cyclic; Phospholipid Transfer Proteins; Virulence Factors

Cryptococcal skin infection in persons with AIDS has been demonstrated. We describe a patient with nasal and facial infection with cryptococci after traumatic injury with battery acid.

Topics: Acids; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Automobiles; Burns, Chemical; Cryptococcosis; Cryptococcus neoformans; Facial Injuries; Fluconazole; HIV-1; Humans; Immunocompromised Host; Male; Medication Adherence; Meningoencephalitis; Middle Aged; Recurrence

A 4-year-old castrated male domestic ferret from central Massachusetts was evaluated for weight loss over a 1.5-month period and for 2 days of retching, diarrhea, and signs of lethargy. It had been housed indoors, with 2 other ferrets, 2 cats, and humans that lacked signs or symptoms of disease.. Physical examination revealed a thin body condition, tachypnea, an increase in respiratory effort, and retching. Splenomegaly was detected during abdominal palpation. Clinicopathologic analysis revealed lymphopenia, lactic acidosis, hypoglycemia, hypocalcemia, hypoalbuminemia, and hyperglobulinemia. A pulmonary bronchointerstitial pattern was evident on radiographs, and abdominal ultrasonography revealed a suspected pancreatic mass and mesenteric lymphadenopathy.. After 2 weeks of medical treatment and once clinical signs resolved, an exploratory laparotomy was performed and a lymph node biopsy specimen was collected. Histologic evaluation of the specimen revealed Cryptococcus-like organisms. Antifungal treatment was initiated with itraconazole (PO) and amphotericin B (IV). The ferret died after 2 days of treatment. A full necropsy was performed, revealing multicentric cryptococcosis affecting the lungs, brain, spleen, and multiple lymph nodes. Paraffin-embedded, formalin-fixed lung tissue was submitted for DNA extraction, and the organism was identified as Cryptococcus neoformans var grubii.. To the authors' knowledge, this is the first report of disseminated cryptococcosis in a North American ferret. This case is unique in that the ferret lived indoors, in a geographic region in which reports of cryptococcosis are rare. The genotyping technique used to identify the Cryptococcus strain can aid in better understanding the epidemiology of cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus; Ferrets; Itraconazole; Male; Pneumonia

Cryptococcus neoformans causes disseminated infection in 7-8% of HIV positive patients admitted to Hospital F. J. Muñiz in Buenos Aires. Meningoencephalitis is the most frequent clinical manifestation and is one of the main causes of death in those patients with AIDS. The standard treatment for this mycosis consists of amphotericin B followed by fluconazole until two successive cultures of CFS are negative. Although resistance to these drugs is infrequent, minimal inhibitory concentrations (MIC) of some antifungals can be high. Since it is important to know the susceptibility levels of this fungus to the antifungal drugs usually employed in our institution, we analyzed the susceptibility test results of C. neoformans with two diffusion methods (Etest and NeoSensitabs tablets) employing Mueller-Hinton agar with 2% glucose and 0.5 microg/ml methylene blue. These results were compared with MICs obtained through the use of the broth microdilution reference method (CLSI). Results showed good agreement with the reference method, with no very major errors and only two major errors for fluconazole using NeoSensitabs tablets. For all the above mentioned, we confirm the usefulness of Mueller-Hinton agar to evaluate C. neoformans susceptibility to amphotericin B and fluconazole with these two agar diffusion methods.

Topics: Amphotericin B; Antifungal Agents; Argentina; Cryptococcosis; Cryptococcus neoformans; Culture Media; Fluconazole; Humans; Microbial Sensitivity Tests; Mycology

Topics: Amphotericin B; Cheek; Cryptococcosis; Cryptococcus neoformans; Facial Dermatoses; Flucytosine; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications

Radioimmunotherapy (RIT) prolongs the survival of mice infected with Cryptococcus neoformans. To compare the efficacy of RIT with that of amphotericin B, we infected AJ/Cr mice intravenously with either nonmelanized or melanized C. neoformans cells. Infected mice were either left untreated or treated 24 h after infection with (213)Bi-18B7 antibody, amphotericin B, or both. Melanization before infection did not increase resistance of C. neoformans to RIT in vivo. (213)Bi-18B7 treatment almost completely eliminated colony-forming units from the lung and brain, whereas amphotericin B did not decrease the number of colony-forming units. We conclude that RIT is more effective than amphotericin B against systemic infection with C. neoformans.

Topics: Amphotericin B; Animals; Antibodies, Fungal; Antifungal Agents; Bismuth; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Female; Lung; Mice; Radioimmunotherapy; Radioisotopes; Treatment Outcome

We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus gattii; Male; Mice; Pyrimidines; Triazoles; Voriconazole

The presence of an opportunistic infection in a patient in sub-Saharan Africa is assumed to be due to underlying immunosuppression from human immunodeficiency virus (HIV) infection. The presence of disseminated cryptococcosis in a non-HIV-infected patient is interesting as it is unique in our setting because the majority of infections are found in HIV-infected individuals. The protean manifestations of the disease and its predilection for immunosuppressed patients make cryptococcosis a challenging and elusive disease to diagnose in HIV-negative patients in our setting, especially due to limited resources. We present a case of disseminated cryptococcosis in an immunocompetent patient and discuss diagnostic and therapeutic features in this subset of patients.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Fluconazole; Humans; Male; South Africa; Tomography, X-Ray Computed

Cryptococcosis most commonly occurs in immunosuppressed patients. The pathogen is the yeast Cryptococcus neoformans. This article reports on the case of a 20-year-old female patient with acute myeloid leukemia who suddenly developed disseminated livid red papules and papulovesicles. The clinical picture and in particular the histopathology findings led to the diagnosis of cutaneous cryptococcosis, which was successfully treated with amphotericin B. For the differential diagnosis generalized herpes zoster, erythema exudativum multiforme and disseminated molluscum contagiosum must be considered. To confirm the diagnosis attempts can also be made to culture the pathogen from skin biopsy preparations. Furthermore, fungal spores can be rapidly and simply detected with the Tzanck test.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Dermatomycoses; Female; Humans; Leukemia, Myeloid, Acute; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Male; Sarcoidosis; Sarcoidosis, Pulmonary; Treatment Outcome

Topics: Adrenal Cortex Hormones; Amphotericin B; Cryptococcosis; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Graft Survival; Humans; Middle Aged; Pemphigus; Preoperative Care; Risk Assessment; Severity of Illness Index; Skin Transplantation; Skin Ulcer; Tissue and Organ Harvesting; Transplantation, Autologous; Treatment Outcome; Wound Healing

Topics: Amphotericin B; Anti-Infective Agents; Cryptococcosis; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Middle Aged; Pleura

To clarify the clinical features and imaging characteristics of non-AIDS patients with pulmonary cryptococcosis.. We retrospectively collected 15 HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep 1992 to Jan 2008. Their medical records and radiological data were reviewed and analyzed.. Only one patient was asymptomatic.Thirteen patients were immunocompetent and two were immunosuppressed. Three patients had associated cryptococcosis meningitis. The most common radiographic abnormalities were multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients respectively. 14 patients received specific therapy for Cryptococcus neoformans. Two patients died. In the 11 patients with isolated pulmonary cryptococcosis, treatment consisted of fluconazole alone (n=7), in combination with amphotericin B (n=2), and both 5-flucytosine and amphotericin B (n=2). For the other 2 patients with cryptococcosis meningitis, one was treated with amphotericin B alone and the other with fluconazole combined with amphotericin B and 5-flucytosine.. Non-AIDS patients might also susceptible to cryptococcosis infection. Histological examination is the principal method of diagnosis. The most common CT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; HIV Seronegativity; Humans; Lung Diseases, Fungal; Male; Middle Aged; Prognosis; Retrospective Studies; Tomography, X-Ray Computed

Cryptococcosis occurs primarily in immunocompromised patients such as organ transplant recipients. Central nervous system and pulmonary infections are documented most frequently; hepatic involvement is rarely reported. We report a case of early hepatic cryptococcosis in a 54-year-old male liver transplant recipient. Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation. Blood and bronchoalveolar lavage cultures were positive for Cryptococcus neoformans. Despite treatment with amphotericin B and flucytosine, the patient developed both marked cholestasis and transaminase elevation. A liver biopsy performed 22 days after admission revealed numerous yeast-like organisms in hepatic sinusoids consistent with C. neoformans. Despite treatment, the patient died 55 days after admission and 66 days after transplantation. Our case illustrates hepatic involvement of cryptococcal infection within the first month following transplantation.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fatal Outcome; Flucytosine; Humans; Immunosuppressive Agents; Liver Diseases; Liver Transplantation; Male; Middle Aged; Postoperative Complications

The in vitro activities of amphotericin B (AmB) were evaluated against 40 isolates of Cryptococcus neoformans using time-kill curves. The isolates were obtained from 20 AIDS patients with cryptococcal meningitis submitted to AmB therapy. Isolates were exposed in vitro to 1 microg/mL of AmB that represents a serum concentration of AmB, and the viable colony counts were determined over time. AmB exhibited fungicidal activity at 6 and 12 h for 70.6% of isolates, at 24 h for 7.3%, and at 48 h for 22% of isolates, respectively. This effect was not maximized when the test drug concentration was up to 4 times the AmB MIC for the isolates. Regrowth was observed in 17.5% of the isolates after fungicidal endpoint. With standard in vitro susceptibility testing, this tolerance phenomenon could not be assessed, and thus, these tests may underestimate the resistance of C. neoformans to AmB in vivo. AmB is the first-choice drug for the treatment of cryptococcosis in Brazil, and future studies using time-kill methodology are needed to estimate the predictive value of this test in the clinical failure.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brazil; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Humans; Microbial Sensitivity Tests; Microbial Viability; Time Factors

Prosthetic joint infections due to Cryptococcus neoformans have not been described before. We report a case of a prosthetic hip joint infection due to C. neoformans. An 84-year-old man with chronic lymphocytic leukemia presented with progressive left groin pain and fever. There was radiographic evidence of prosthesis loosening, and an aspirate of the left hip joint grew C. neoformans. The patient was treated with amphotericin B with good initial symptomatic response. The patient elected not to undergo revision arthroplasty, and oral suppressive therapy with fluconazole was initiated. After 10 months of fluconazole therapy, the prosthesis was removed secondary to pain and increased instability of the implant. Despite excellent penetration of fluconazole into the joint fluid and reports of successful outcome in patients with native joint cryptococcal infections as well as prosthetic joint infections due to Candida spp., suppressive fluconazole therapy failed. The failure may have been due to an unfavorable interaction between the organism and immune mechanism as well as reduced activity of fluconazole in biofilm.

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Arthroplasty, Replacement, Hip; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Hip; Humans; Male; Prosthesis-Related Infections; Radiography

A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalization.

Topics: Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Culture Media; DNA, Fungal; DNA, Ribosomal Spacer; Drainage; Female; Fluconazole; Flucytosine; Humans; Meningoencephalitis; Middle Aged; Molecular Sequence Data; Phylogeny; Sequence Analysis, DNA; Switzerland; Travel

The impact of current transplantation practices on the characteristics of cryptococcosis in solid-organ transplant recipients is not well defined. The incidence of cryptococcal disease among solid-organ transplant recipients has remained unchanged; however, patients are less likely to present with central nervous system or disseminated disease and are more likely to have cryptococcosis limited to the lungs. Additionally, lipid formulations of amphotericin B are now used more frequently, whereas their use in combination with flucytosine has decreased. The overall mortality of cryptococcosis has significantly improved in the current era. Renal failure remains associated with poor outcome, whereas use of lipid formulations of amphotericin B is associated with a higher survival rate. Despite rare infectious complication, certain peculiar attributes of cryptococcal disease in hematopoietic stem cell recipients and tissue transplant recipients warrant recognition.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Organ Transplantation; Renal Insufficiency; Tissue Transplantation

Cryptococcosis is a disseminated fungal disease typically associated with immunosuppression and characterized by high mortality rates. Cryptococcus neoformans has been reported to be isolated from blood cultures in around 20% of patients with cryptococcosis, and cryptococcemia has been correlated with poor prognosis. We report a case of fatal C. neoformans fungemia in a neutropenic patient with a history of chronic lymphocytic leukemia treated with alemtuzumab. The patient presented with loss of consciousness and died after 5 days of antifungal therapy with liposomal amphotericin B. The international literature regarding opportunistic infections after immunosuppressive therapy with alemtuzumab with particular attention on fungal infections has also been reviewed.

Topics: Aged; Alemtuzumab; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antifungal Agents; Antineoplastic Agents; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Fungemia; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neutropenia; Opportunistic Infections

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Eye Diseases; Eye Infections, Fungal; Fluconazole; Flucytosine; Humans; Male; Middle Aged; Ultrasonography; Vitrectomy; Vitreous Body

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

Cryptococcosis, a fatal disease without appropriate treatment, is still one of the major opportunistic mycoses in AIDS patients in Argentina despite the availability of high active anti-retroviral therapy (HAART). Over the last decade, drugs employed in the treatment of disseminated cryptococcosis at Infectious Diseases Hospital "F.J. Muñiz" included amphotericin B (AMB) followed by fluconazole (FCZ), due to the fact that flucytosine was not available in Argentina during this period. A considerable number of patients did not negativize cultures after 2-3 weeks of treatment as it was expected, and in some of them the isolation of Cryptococcus neoformans in different samples was still possible after 2 or more months of adequate therapy and even in cases with clinical improvement. The aim of this study was to establish the susceptibility profile of C. neoformans clinical isolates to those antifungals and to investigate whether there were any changes after at least 2 months of treatment. A total of 265 strains were studied (116 obtained from patients at diagnosis and 149 corresponding to the same individuals 2 months or more after receiving therapy). Susceptibility patterns before treatment to AMB showed MICs < or =1 microg/ml for all the strains, and no increase was seen after treatment. All the strains were susceptible to FCZ (MIC< or =8 microg/ml) at diagnosis; but in a group with relapses or those who did not negativize cultures, one isolate became resistant after therapy (MIC> or =64 microg/ml) and other four showed dose-dependent susceptibility (MIC 16-32 microg/ml). There was no relation between these results and clinical outcome as it was pointed out in other publications.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; HIV Seropositivity; Humans; Male; Microbial Sensitivity Tests; Time Factors

Cryptococcus neoformans is a yeastlike encapsulated basidiomycetous fungus that is able to cross the blood-brain barrier and cause meningitis in both immunocompetent and immunocompromised individuals. Cryptococcus neoformans has emerged as a major opportunistic pathogen because of the widespread use of immunosuppressive therapy. It causes most cryptococcal infections in humans, and disseminated infection can have cutaneous manifestations. We report a rare case of disseminated C neoformans in a 52-year-old man who underwent an orthotopic liver transplant. We also provide a concise review of the literature on C neoformans, including its associations, histology, and treatment.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Liver Transplantation; Male; Middle Aged; Treatment Outcome

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

Cutaneous cryptococcosis, caused by an encapsulated yeast, Cryptococcus neoformans, is generally associated with concomitant systemic infection. Here we report a case of primary cutaneous cryptococcosis with spread to central nervous system in an HIV seronegative young boy. In the present case, a 17-year-old boy who was suffering from a non-healing ulcer on his right great toe for 5 months, presented with the signs and symptoms of meningitis. Cryptococcus neoformans var. gattii was isolated from the CSF of the patient. Amphotericin B administration produced recovery from the meningitis as well as from the ulcer. This case study suggests that primary cutaneous cryptococcosis can be diagnosed provisionally by a simple Gram stained smear and India ink examination in order to avoid occurrence of disseminated cryptococcosis, including meningial involvement, which may have a fatal outcome.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Carbon; Coloring Agents; Cryptococcosis; Cryptococcus gattii; Dermatomycoses; Fluconazole; Foot Ulcer; Fungemia; Gentian Violet; HIV Seronegativity; Humans; Male; Meningitis, Cryptococcal; Phenazines; Staining and Labeling; Toes

This is the first case reported of central venous catheter-related fungemia due to C. neoformans. A patient with chronic renal failure developed a fungemia during the treatment of a dialysis-associated bacteremia. Cryptococcus neoformans grew in the catheter tip and blood culture. We addressed questions about this catheter-related fungemia.

Topics: Amphotericin B; Antifungal Agents; Catheter-Related Infections; Catheterization, Central Venous; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Female; Fungemia; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis

Cuban Cryptococcus isolates (n = 165) were tested in vitro against amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole, giving MIC90 values of 0.25, 8, 4, 0.25, 0.125, 0.016, and 0.016 microg/ml, respectively. Isavuconazole and posaconazole seem to be potentially active drugs for treating cryptococcal infections.

Topics: Antifungal Agents; Azoles; Cryptococcosis; Cryptococcus neoformans; Cuba; Humans; Microbial Sensitivity Tests; Nitriles; Pyridines; Triazoles

The in vitro and in vivo antifungal activities of T-2307, a novel arylamidine, were evaluated and compared with those of fluconazole, voriconazole, micafungin, and amphotericin B. T-2307 exhibited broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 microg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 microg/ml), and Aspergillus species (MIC range, 0.0156 to 4 microg/ml). Furthermore, T-2307 exhibited potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains. T-2307 exhibited fungicidal activity against some Candida and Aspergillus species and against Cryptococcus neoformans. In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the 50% effective doses of T-2307 were 0.00755, 0.117, and 0.391 mg.kg(-1).dose(-1), respectively. This agent was considerably more active than micafungin and amphotericin B against candidiasis and than amphotericin B against cryptococcosis, and its activity was comparable to the activities of micafungin and amphotericin B against aspergillosis. The results of preclinical in vitro and in vivo evaluations performed thus far indicate that T-2307 could represent a potent injectable agent for the treatment of candidiasis, cryptococcosis, and aspergillosis.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Benzamidines; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses; Specific Pathogen-Free Organisms; Treatment Outcome

SPK-843, a new polyene antifungal, possessed efficacy in a murine model of systemic infection caused by Cryptococcus neoformans. The administration of 4.0 mg/kg SPK-843 led to better survival prolongation and fungal reduction than those observed with the administration of 0.7 mg/kg amphotericin B and 80 mg/kg fluconazole (P < 0.001), without histopathological renal changes.

Topics: Animals; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Polyenes

Topics: Amphotericin B; Antifungal Agents; Bone Marrow; Candida albicans; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Interferon-gamma; Male; Receptors, Interleukin-12

The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals.. Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030) were independently associated with treatment failure at Mo3.. Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Flucytosine; HIV Seropositivity; Humans; Male; Societies, Medical; Treatment Outcome; United States

A 23-year-old man with no recent medical history was hospitalized complaining of high fever and cough. In addition to very marked eosinophilia, chest X-ray revealed extensive bronchovascular bundle thickening. Transbronchial lung biopsy (TBLB) showed moderate eosinophil infiltration. Cryptococcus neoformans infection was diagnosed, based on blood culture, cerebrospinal fluid culture, urine culture, and lung biopsy specimens. The eosinophilia was successfully alleviated by treatment for cryptococcal meningitis. Furthermore, cryptococcal sepsis resolved with amphotericin B and 5-flucytosine treatment. Eosinophilia commonly occurs following chronic Aspergillus infection, but the present case suggests the involvement of Cryptococcus in another mechanism for eosinophilia.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Eosinophilia; Flucytosine; Humans; Lung Diseases, Fungal; Lymph Nodes; Male; Radiography

Disseminated cryptococcosis is a well-known opportunistic infection in AIDS patients. We report an unusual patient who demonstrated an isolated plaque of cryptococcosis on the penis. Resolution of this plaque was obtained after treatment with fluconazole, but subsequent cutaneous dissemination occurred that was responsive to amphotericin B.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Biopsy, Needle; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Follow-Up Studies; Humans; Immunohistochemistry; Infusions, Intravenous; Male; Penis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. It is more common among immunosupressed patients such as human immunodeficiency virus (HIV) positive ones. In this report we present a case with C. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV infection. A-70-years-old male was admitted to the hospital with mental confusion, 3-weeks history of headache, weight loss, dry cough and fatigue. Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF) white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF revealed poorly stained gram-positive yeast cells. Empirical therapy with lipozomal amphotericin B, ceftriaxone and ampicillin combination was started. When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin were discontinued. Patient became conscious at 24th hour of the treatment. Peripheric blood flow-cytometric analysis revealed a significant decrease in absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a significant increase in natural killer cell ratio. Blood immunoglobulin and complement levels were found normal. Cranial magnetic resonance imaging and computerized tomogralphy (CT) of the abdomen were normal, however, chest CT revealed multiple parenchymal millimetric nodular infiltrations on both sides and minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture, tuberculosis PCR results and repeated HIV serology were found negative. Despite the lack of microbiological confirmation, empirical antituberculosis treatment was also started with the suspicion of miliary tuberculosis as the patient had a symptom of long-term dry cough, miliary infiltrations on chest CT, anergic tuberculin skin test and a history of pulmonary tuberculosis in childhood. After two weeks, amphotericin B was changed to oral fluconazole which was continued for an additional eight weeks. Antituberculosis therapy was given for nine months. Control chest CT taken after four months of antituberculosis therapy revealed improvement of the lesions. This presentation emphasizes the fact that cryptococcal infections may develop in HIV negative patients, even together with tuberculosis in certain cases and radiological findings of the two infections may

Topics: Aged; Amphotericin B; Antifungal Agents; Antitubercular Agents; CD4-CD8 Ratio; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; HIV Seronegativity; Humans; Leukocyte Count; Male; Tuberculosis, Miliary

Cryptococcosis is a rare infection with high mortality in patients who have undergone heart transplantation (HT). In this study, we report four cases of the disease selected from our 328 HT cases (1.22%) between 1987 and 2007. The purpose of this study was to review risk factors for cryptococcosis after HT. Three of the four patients were men. The mean time from HT to diagnosis was 8.5 months (range, 3-17 months). Cryptococcosis was subcutaneous in one patient, systemic in one, and meningeal in two. One patient died. The Antifungal regimens included intravenous amphotericin B (amBisone) and oral fluconazole (Diflucan). Patients with diabetes mellitus or renal insufficiency, are hepatitis B carriers, have undergone repeat HT, or are receivings steroid therapy are susceptible to cryptococcosis. The recommend anticryptococcal therapy is amphotericin B, followed by oral fluconazole for at least 6 months. Early diagnosis with aggressive diagnostic techniques and a combination of therapies must be considered to reduce the risk of death in HT recipients with cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Fluconazole; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Meningitis, Cryptococcal; Middle Aged; Postoperative Complications; Risk Factors

Neonatal infection due to Cryptococcus neoformans is extremely rare. We report a case of a 21-day-old neonate diagnosed with cryptococcal septicemia who was successfully treated with amphotericin B. He was born to a human immunodeficiency virus (HIV) seronegative mother. This report alerts general pediatricians and neonatologists to consider Cryptococcus neoformans infection as a possible cause of sepsis in newborn infants.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Immunocompetence; Infant, Newborn; Male; Sepsis

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Edema; Fever; Humans; Immunocompromised Host; Male; Polyarteritis Nodosa; Skin Diseases

We experienced a rare case of colonic cryptococcosis in an apparently immunocompetent individual. A 27-year- old woman admitted our hospital for intermittent melena. Initial abdominal CT scan revealed a mass lesion obstructing most of the lumen in ascending colon. Colonoscopy showed huge ulcerofungating mass in proximal ascending colon. Colonoscopic biopsy was performed and pathologic diagnosis was made as colonic cryptococcosis with positive PAS stain. Laboratory test evaluating immune status and bone marrow examination was normal. The patient was treated with intravenous amphotericin B for four weeks and six months of oral fluconazole afterwards. Follow-up abdominal CT scan and colonoscopy were taken at four weeks and seven months after the beginning of treatment. On completion of intravenous amphotericin B treatment, the mass lesion was decreased in abdominal CT and colonoscopy. After seven months, abdominal CT and colonoscopy showed near-complete resolution of the colonic lesion so the treatment ended. Cryptococcosis in a healthy individual is a rare disease and there have been only several sporadic case reports on pulmonary or central nervous system involvement. Hence, we report a case of colonic cryptococcosis in an apparently immunocompetent individual.

Topics: Adult; Amphotericin B; Antifungal Agents; Colonic Diseases; Colonoscopy; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Injections, Intravenous; Tomography, X-Ray Computed

Pulmonary cryptococcosis can be clinically silent in non-HIV infected patients but can also present as nodules and masses on the chest radiograph, which can be mistaken for tuberculosis or lung cancer. Common symptoms include fever and cough, and uncommonly haemoptysis. This report illustrates a non-HIV infected patient whose main complaint was haemoptysis and headache. He was diagnosed with pulmonary cryptococcosis from biopsy of an endobronchial mass found on flexible bronchoscopy. Disseminated cryptoccoccal infection should be considered as a differential diagnosis in non-HIV infected patients presenting with haemoptysis and headache. Early recognition and administration of appropriate therapy will improve clinical outcome in these patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Diagnosis, Differential; Fluconazole; Headache; Hemoptysis; Humans; Lung Diseases, Fungal; Lung Neoplasms; Recurrence

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cryptococcosis; Haiti; Humans; Lymphopenia; Male; Skin Diseases, Vesiculobullous

A 57-year-old Japanese man complained of pain on micturition. The prostate was of normal size but hard. Transrectal needle biopsy demonstrated granulomatous prostatitis with small focal abscesses. Staining with periodic acid-Schiff, Grocott's methenamine silver and Fontana-Masson revealed yeast-form fungus in the granulomas. The mucoid capsule of the fungus stained with mucicarmine. PCR specific for cryptococcal 18S rDNA using DNA extracted from the pathological specimen was positive, and the sequence was homologous to Cryptococcus neoformans. A diagnosis of cryptococcal granulomatous prostatitis was made. The patient was then found to suffer from meningitis and lung abscess, and was treated with amphotericin B and flucytosine. Careful histological and molecular studies are beneficial to reach the correct diagnosis and to prevent an unfavorable outcome of disseminated cryptococcosis.

Topics: Abscess; Amphotericin B; Antifungal Agents; Carmine; Coloring Agents; Cryptococcosis; Cryptococcus neoformans; DNA, Fungal; DNA, Ribosomal; Drug Therapy, Combination; Flucytosine; Granuloma; Humans; Lung Diseases, Fungal; Male; Meningitis, Cryptococcal; Methenamine; Middle Aged; Periodic Acid-Schiff Reaction; Prostatitis; Ribotyping; RNA, Fungal; RNA, Ribosomal, 18S; Silver Nitrate; Staining and Labeling

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

This study analysed the spectrum, antifungal susceptibility pattern, clinical course and molecular epidemiology of cryptococcosis. Four hundred and thirty-nine samples obtained from 378 meningitis patients were processed by standard procedures. Minimum inhibitory concentration (MIC) of fluconazole and amphotericin B for the isolates was tested by broth micro dilution and by E-strip method. Molecular analysis by random amplified polymorphic DNA-PCR of eight isolates was performed using M13 primer. Cryptococcosis was diagnosed in 35 patients [HIV-1 seropositive (19) and apparently immunocompetent (16)]. Cryptococcus neoformans var. neoformans (serotype A and D) was the predominant isolate on phenotypic identification. Three C. neoformans var. gattii were isolated from HIV-1 seropositive (2) and apparently immunocompetent (1) patients. MIC 90 for amphotericin B and fluconazole were 1 and 8 mug ml(-1) respectively. On RAPD-PCR, less diversity was seen among Indian isolates. AIDS remains the single most important risk factor for cryptococcosis. Rising MIC of the available induction and maintenance drugs is of grave concern. The DNA typing technique showed less diversity among Indian strains. Routine surveillance and application of molecular typing methods are crucial to know the baseline and existing pattern of cryptococcosis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; DNA Primers; DNA, Fungal; Fluconazole; Humans; India; Microbial Sensitivity Tests; Molecular Epidemiology; Mycological Typing Techniques; Random Amplified Polymorphic DNA Technique

Topics: Amphotericin B; Antifungal Agents; Blood Pressure; Cardiomyopathies; Cryptococcosis; Drug Carriers; Electrocardiography; Female; Flucytosine; Heart; Heart Function Tests; Heart Rate; Humans; Liposomes; Middle Aged; Radionuclide Imaging

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Colitis; Colonoscopy; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Drug Therapy, Combination; Flucytosine; Humans; Injections, Intravenous; Intestinal Mucosa; Male

Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans.. The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9-7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy.. Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; France; Humans; Male; Meningoencephalitis; Prospective Studies; Severity of Illness Index; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Cryptococcosis; Debridement; Fasciitis, Necrotizing; Fatal Outcome; Humans; Male; Middle Aged; Soft Tissue Infections; Subcutaneous Tissue; Thigh

Environmental fungi, in particular primary pathogens and Cryptococcus spp. can be responsible for skin lesions mimicking sporotrichosis. In this paper, we report a case of subcutaneous cryptococcosis in an apparently healthy, young male patient due to a non-C. neoformans Cryptococcus species, C. diffluens. The isolate showed in vitro phenotypic switching that may affect virulence and host inflammatory and immune responses, and in vitro resistance to amphotericin B and 5-flucytosin. This species shares several phenotypic traits with C. neoformans, and, therefore, decisive diagnosis should be based on biopsy and culturing results followed by molecular identification.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Base Sequence; Cryptococcosis; Cryptococcus; Diagnosis, Differential; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Drug Resistance, Fungal; Flucytosine; Humans; Male; Microbial Sensitivity Tests; Molecular Sequence Data; RNA, Ribosomal, 28S; Sequence Analysis, DNA; Sporotrichosis

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

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Candidiasis; Cryptococcosis; Drug Combinations; Fungemia; Humans; Phosphatidylcholines; Phosphatidylglycerols; Viscera

Increase in cryptococcal infection has been noticed after acquired immunodeficiency syndrome pandemic. Cryptococcus neoformans can be isolated from blood in the process of dissemination to brain. We report a case of cryptococcal fungaemia in a patient whose cerebrospinal fluid was negative for Cryptococcus neoformans. Retrospective analysis revealed human immunodeficiency virus seropositivity of the patient. He was treated with amphotericin B and fluconazole. Antiretroviral therapy was started, however, the patient succumbed to the infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Fungemia; HIV Seropositivity; Humans; Male; Meningoencephalitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Fatal Outcome; Fluconazole; Humans; Immunocompromised Host; Male; T-Lymphocytopenia, Idiopathic CD4-Positive; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fungemia; Hepatitis B, Chronic; Hepatomegaly; Herpes Zoster; Histoplasmosis; Humans; Male; Splenomegaly; Toxoplasmosis; Ultrasonography; Uremia

Cryptococcal spinal arachnoiditis occurs in patients with meningitis and usually when they are immunocompromised. Spinal symptoms in cryptococcosis are rare and a very exceptional entity in the immunocompetent population. We present a young immunocompetent male who developed progressively increasing paraparesis due to primary cryptococcal arachnoiditis, who showed significant improvement after antifungal therapy. Although extremely rare, spinal arachnoiditis in an immunocompetent individual can be caused due to cryptococcus, as in our case. This case illustrates and emphasizes the necessity for an exhaustive and complete investigation, with a high index of suspicion for fungal etiology in patients presenting with spinal arachnoiditis or other disabling, progressive spinal cord syndromes of unknown etiology. Awareness of this presentation is necessary to avoid delay in diagnosis and management of this potentially curable condition.

Topics: Amphotericin B; Arachnoiditis; Biopsy; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Granuloma; Humans; Infusions, Intravenous; Low Back Pain; Magnetic Resonance Imaging; Male; Sacrum; Spinal Diseases; Tuberculosis, Spinal

To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients.. HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed.. During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%.. Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diabetes Complications; Female; Fluconazole; Health Surveys; HIV Infections; HIV Seronegativity; Hospitals, University; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Male; Middle Aged; Neoplasms; Retrospective Studies; Thailand; Treatment Outcome

Fungal infections develop slowly in immunocompetent patients and rarely a severe disease, however, they progress rapidly and usually prove fatal in immunocompromised patients. Early diagnosis and treatment of fungal infections is essential to survival of immunocompromised patients. We report a 33-year-old woman with systemic lupus erythematosus undergoing immunotherapy infected with combined invasive pulmonary aspergillosis and pulmonary cryptococcosis diagnosed by video-assisted thoracic surgery lung biopsy and she was successfully treated as a result of early diagnosis and treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Female; Fluconazole; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Diseases, Fungal; Lupus Erythematosus, Systemic

Whether or not flucytosine should be administered to patients infected with Cryptococcus neoformans isolates found to be resistant to flucytosine in vitro remains a controversial issue. Thus, the efficacy of amphotericin B and flucytosine in combination was investigated by mortality and fungal burden studies in a murine model of disseminated cryptococcosis using two clinical isolates of Cryptococcus neoformans, one susceptible and one resistant (i.e., 64 microg/ml) to flucytosine. Amphotericin B was given intraperitoneally at 0.25 or 0.5 mg/kg/day, while flucytosine was given at 100 or 250 mg/kg/day orally. Treatment was started 24 h or day 6 after inoculation and continued for 5 days in fungal burden and mortality studies, respectively. The combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day was significantly more effective than monotherapies for reducing fungal burden in brain, spleen, and lungs after infection by the flucytosine-susceptible isolate and in brain and spleen for the flucytosine-resistant isolate. For the flucytosine-resistant isolate, the combination of amphotericin B at 0.5 mg/kg/day with flucytosine at 100 mg/kg/day was significantly better than monotherapies for reducing the fungal burden in the brain. Survival obtained after the combination of amphotericin B at 0.5 mg/kg/day and flucytosine at 250 mg/kg/day increased compared to that obtained with monotherapies for both isolates, but the difference was statistically significant only for the flucytosine-susceptible isolate. Antagonism was never observed. This study demonstrates the beneficial effect of the addition of flucytosine to amphotericin B against experimental disseminated cryptococcal infection even when the C. neoformans isolate is resistant to flucytosine.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Flucytosine; Lung

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Cytodiagnosis; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Fluconazole; Humans; Male; Middle Aged; Skin

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Dermatomycoses; Diagnosis, Differential; Humans; Immunocompromised Host; Male; Middle Aged

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Dermatomycoses; Female; Humans; Immunocompetence; Itraconazole

Disseminated cryptococcosis mainly occurs in patients with impaired cell mediated immunity. We present a case of disseminated cryptococcosis in a non-HIV patient with nephrotic syndrome who never received immunosuppression. Cultures of bone marrow aspirate, cerebrospinal fluid analysis and histology of skin lesions were all consistent with Cryptococcus neoformans infection. Treatment with amphotericin B followed by fluconazole was successful and in the course of two months when, the skin nodules disappeared.

Topics: Adult; Amphotericin B; Antifungal Agents; Bone Marrow; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Forearm; Humans; Male; Nephrotic Syndrome; Skin; Treatment Outcome

Conventional amphotericin B has been the 'gold standard' for antifungal efficacy, but nephrotoxicity problems limit its clinical utility. In the late 1990s, three lipid-based formulations of amphotericin B were introduced, all of which offered comparable efficacy and reduced renal complications. However, to date, robust safety and comparative efficacy data have been sparse. This paper briefly reviews the available clinical data on amphotericin B lipid complex (ABLC). Also, in detail, it reviews the findings of Collaborative Exchange of Antifungal Research (CLEAR), the most extensive dataset on systemic antifungal treatment with the lipid-based agent ABLC.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Clinical Trials as Topic; Cryptococcosis; Databases, Factual; Drug Combinations; Humans; In Vitro Techniques; Multicenter Studies as Topic; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Prospective Studies; Treatment Outcome; Zygomycosis

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Drug Resistance, Fungal; Fluconazole; Fungi; Humans; In Vitro Techniques; Itraconazole; Microbial Sensitivity Tests; Mycoses; Pyrimidines; Triazoles; Voriconazole

The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Predictive Value of Tests; Prognosis; Treatment Outcome

To compare the MICs of FLUconazole (FLU) and amphotericin B against isolates of Cryptococcus neoformans (C. neoformans) obtained from the CerebroSpinal Fluid (CSF); and clinical outcomes of HIV-infected patients diagnosed with cryptococcal meningitis.. There were two groups including those who did not receive FLU (group A) and those who did receive either FLU 400 mg/week for primary prophylaxis cryptococosis or 200 mg/day for secondary prophylaxis cryptococosis (group B). CSF isolates of C. neoformans from group A and group B between January 2003 and October 2004 were retrospectively studied. The MICs were determined by using the standard NCCLS broth microdilution methods (M27-A). The MICs of FLU and amphotericin B, and clinical outcomes after 10 weeks of cryptococcal meningitis treatment were determined.. There were 98 isolates; 80 in group A and 18 in group B. The patients in group B had a higher proportion of previous opportunistic infections (p = 0.008). The other baseline characteristics between the two groups were not different. The median (range) MIC of FLU was 8.0 (0.5-32) microg/ml in group A, and 6.0 (0.5-32) microg/ml in group B (p = 0.926). The median (range) MIC of amphotericin B was 0.25 (0.03-1.0) microg/ml in group A, and 0.25 (0.12-1.0) microg/ml in group B (p = 0.384). Sixty patients from group A and 14 from group B received standard treatment and continued to follow-up. After the 10-week treatment, 39/60 (65%) patients in group A and 7/14 (50%) in group B had complete recovery (p = 0.364; RR = 0.538, 95%CI = 0.166-1.742). The overall mortality rate was 14/60 (23.3%) in group A and 7/14 (50.0%) in group B (p = 0.096; RR = 3.286, 95%CI = 0.983-10.979).. The MICs of FLU and amphotericin B against CSF isolates of C. neoformans and clinical outcomes between HIV-infected patients who receive or did not receive FLU prophylaxis are not different.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

Cutaneous infections is observed in 15% of patients with disseminated cryptococcosis with AIDS. We present here a case of a 34 years old female with AIDS. She presented with multiple skin coloured umbilicated over face, neck, trunk and limbs, which mimicked molluscum contagiosum and kaposi sarcoma. The tissue from cutaneous lesions was collected by excision biopsy and processed by standard mycological methods. Cryptococcus neoformans was isolated and identified. Cerebrospinal fluid (CSF) also yielded the growth of C. neoformans . Cryptococcal antigen was detected with a titre of 1024 by Latex agglutination, is serum and CSF. Her serum was reactive for HIVI and 2 antibodies. The CD4 lymphocytes count was 80/cmm. The HIV viral load was 2,48,084 copies/mL. She was treated with amphotericin B injectable and oral fluconazole. She responded well and lesions regressed.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Female; Fluconazole; Humans; Male

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Humans; Itraconazole

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcosis; Diagnosis, Differential; Fluconazole; Flucytosine; HIV Seropositivity; Humans; Male; Molluscum Contagiosum

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Facial Dermatoses; Female; Flucytosine; HIV Infections; Humans; Pruritus; Radiography

In cryptococcal infection, phenotypic switching from a smooth to a mucoid variant can occur in vivo, producing variants with enhanced virulence that are subsequently selected and affect the outcome of infection. Here, we demonstrate that antifungal treatment of the chronically infected host can promote this phenomenon. Amphotericin B treatment reduces fungal burden less effectively in mucoid variant-infected than in smooth variant-infected mice. Consequently, amphotericin B treatment resulted in a more pronounced prolongation of survival in smooth variant-infected than in mucoid variant-infected mice (20 versus 42 days; P < 0.05). Administration of anticapsular monoclonal antibody mediated better protection in smooth variant-infected than in mucoid variant-infected mice, although a protective effect was not consistently observed at all doses. Most interestingly, both antifungal drug therapy and administration of anticapsular monoclonal antibody promoted the selection of mucoid variants in smooth variant-infected mice, a phenomenon manifested by a statistically higher percentage of mucoid colonies in smooth variant-infected mice than in nontreated control mice. This finding suggests that both chemotherapeutic and immunological antifungal interventions may promote the selection of the more virulent mucoid variant, which could affect the outcome of infection in chronically infected hosts.

Topics: Amphotericin B; Animals; Antibodies, Fungal; Antifungal Agents; Chronic Disease; Cryptococcosis; Cryptococcus neoformans; Humans; Lung Diseases, Fungal; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Phenotype; Treatment Outcome; Virulence

Disseminated cryptococcal disease is typically seen in patients with HIV infection. We report here the evolution of a patient with disseminated cryptococcosis whose treatment failed after ten weeks of induction therapy with amphotericin B. This case illustrates the importance of careful initial evaluation, and close clinical follow-up of these patients who are at risk of developing other opportunistic infections and drug-related complications.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Diagnosis, Differential; Female; Fluconazole; HIV Seropositivity; Humans; Skin

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Dermatomycoses; Fluconazole; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Time Factors; Treatment Outcome

The efficacy and renal safety of amphotericin B lipid complex (ABLC) injection were assessed in 106 patients with cryptococcal infection. Eighty-three patients (78%) had a central nervous system (CNS) infection. Of these patients, 20 initiated azole therapy concomitantly with ABLC therapy, and 7 had received prior azole therapy, which continued during administration of ABLC. Clinical response (cured or improved) was achieved in 67 (66%) of 101 patients whose results could be evaluated. Response rates were 65% (51/78) for patients with a CNS infection and 70% (16/23) for patients without a CNS infection. The response rate for patients with HIV infection was 58% (30/52). Response rates were 56% (19/34) for patients who were refractory to prior antifungal therapy, 65% (11/17) for patients who were intolerant of prior antifungal therapy, 60% (3/5) for patients with underlying renal disease who received prior antifungal therapy, 76% (25/33) for patients with underlying renal disease who did not receive prior antifungal therapy, and 73% (8/11) for patients with no renal disease who did not receive prior antifungal therapy. A mean serum creatinine level decrease of 0.02 mg/dL occurred. ABLC was an effective treatment for cryptococcal infection in immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Combinations; Female; Humans; Immunocompromised Host; Male; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Registries; Treatment Outcome

A 66-year-old woman with malignant lymphoma became neutropenic during chemotherapy and developed cryptococcemia. After amphotericin B had been commenced, she developed significant hypokalemia and polyuria, though her renal function remained stable. The laboratory findings showed no evidence of renal tubular acidosis. With vigorous water and potassium replacement, amphotericin B had been continued until the cumulative dose reached 2.5 g. After the cessation of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on theses findings, she was diagnosed as nephrogenic diabetes insipidus with hypokalemia and without renal tubular acidosis due to amphotericin B. This complication is usually reversible, and vigorous water and potassium replacement may allow completion of treatment by amphotericin B, though careful monitoring of body water balance and renal function is of importance.

Topics: Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; Antimetabolites, Antineoplastic; Bacteremia; Cryptococcosis; Cryptococcus neoformans; Diabetes Insipidus, Nephrogenic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lymphoma; Mercaptopurine; Tomography, X-Ray Computed

We report two cases of cutaneous cryptococcosis in male patients without underlying disease. Case 1 had a granulomatous mass on his right neck, gradually enlarging for 3 months. After the mass was debrided surgically in a hospital, the incision wound gradually developed into a severe ulceration. Mycological examination revealed Cryptococcus neoformans infection. It was significant that histopathology of both pre-surgery granuloma and post-surgery ulceration revealed thick-walled spores with thick capsule. Chest X-ray revealed a shadow in the left lower lung. After treatment with amphotec for 21 days, the lesion healed. Case 2 had an approximately 2 x 2 cm solitary dull nodule on his right thigh, which had been present for 8 months. Mycological examination confirmed that the lesion was caused by C. neoformans. The patient's ratio of peripheral blood CD4(+) cell was slightly reduced. After 14 days of treatment with oral fluconazole, followed by oral itraconazole for 2 months, mycological and clinical cure were achieved. The two isolates were identified as C. neoformans var. gattii serotype C and C. neoformans var. grubii serotype A.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fluconazole; Granuloma; Humans; Itraconazole; Male; Neck; Spores, Fungal; Thigh

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

The role of the immunomodulator tuftsin in enhancing the antifungal activity of liposomal amphotericin B against Cryptococcus neoformans in leucopenic mice was assessed.. In the present study, we investigated the antifungal activity of amphotericin B liposomes with tuftsin grafted on the surface. Mice were treated with free amphotericin B as well as liposomal formulations after C. neoformans infection. For prophylactic studies, mice were pre-treated with liposomal tuftsin (50 microg/mL) for three consecutive days prior to C. neoformans infection (7 x 10(5) cfu/mouse). Chemotherapy, with tuftsin-free and tuftsin-bearing amphotericin B liposomes, was started 24 h post C. neoformans infection. The role of tuftsin in immunoaugmentative therapy was assessed by survival and cfu of treated mice.. Amphotericin B entrapped in tuftsin-bearing liposomes showed increased anticryptococcal activity in the murine model. Moreover, tuftsin pre-treatment further augmented the antifungal activity of liposomal amphotericin B in leucopenic mice. Incorporation of tuftsin in liposomes resulted in increased anticryptococcal activity of liposomal amphotericin B compared with amphotericin B deoxycholate and conventional liposomal amphotericin B formulations.. The enhanced anticryptococcal activity of amphotericin B in tuftsin-liposomes can be attributed to the immune-stimulating property of tuftsin. Tuftsin activates the key immune cells, due to the presence of its receptors on macrophages and neutrophils, for a better fight against pathogens. Simultaneous liposome-mediated delivery of amphotericin B to the site of infection kills the pathogens more effectively.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Dose-Response Relationship, Drug; Drug Synergism; Immunologic Factors; Leukocytes; Leukopenia; Liposomes; Lung; Mice; Mice, Inbred BALB C; Tuftsin

Cryptococcosis is a polymorphous disease occurring especially in the course of the Acquired Immuno Deficiency Syndrome (AIDS). It puts so diagnostic that therapeutical problems in African countries. The objective of this observation is to report a case of nasal localization with a cutaneous cryptococcosis. It has been confirmed by the histopathologic study of the cutaneous biopsy. The patient was 42 year-old female, HIV positive, bachelor and hospitalised for epistaxis with cutaneous tumefaction and lesions of the nose. The rate of CD4 was 98/mm3. The treatment was based on amphotericine B. Patient died from neuro meningitis extension of the disease.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Female; Humans; Injections, Intravenous; Nose Diseases

Antifungal drugs can affect the cellular morphology of Cryptococcus neoformans in culture, which alters its interactions with phagocytes. We examined the effects of amphotericin B on C. neoformans during murine infection. The antifungal reduced capsule size and serum polysaccharide, which suggests an additional mechanism for amphotericin B's efficacy in cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cell Size; Cryptococcosis; Cryptococcus neoformans; Female; Mice; Mice, Inbred C57BL

The co-administration of immunomodulators and antibiotics has been proved very successful for treatment of opportunistic infectious diseases. In the present study, we evaluated the combination of liposomal amphotericin B (lip-Amp B) and immunomodulator tuftsin to cure Cryptococcus neoformans infection in BALB/c mice. Mice infected with C. neoformans were treated with Amp B deoxycholate and tuftsin free or tuftsin-loaded Amp B liposomes. The results of the present study demonstrated higher efficacy of tuftsin-loaded Amp B liposomes against experimental murine cryptococcosis, in terms of enhanced survival rate and reduced fungal burden in organs (lungs and brain) of the treated mice. Interestingly, pre-treatment of mice with liposomal tuftsin before challenging them with the C. neoformans infection resulted in 100% survival of the treated animals followed by treatment with lip-Amp B. Immunomodulator-based therapy seems likely to be more beneficial for treatment of fungal infectious diseases.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Immunocompetence; Immunologic Factors; Liposomes; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Tuftsin

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis. It occurs almost exclusively in the late posttransplantation period (>6 months after the initiation of immunosuppression). Subclinical onset of meningitis is the usual clinical presentation. Despite initiation of therapy, the mortality rate associated with this infection in this patient population remains high. To the best of our knowledge, this report describes one of the first cases of a rare entity: a primary cutaneous cryptococcosis in a renal transplant recipient disclosed by skull osteomyelitis and pseudotumoral intracranial extension. Surgical debridement and azole antifungal therapy were performed. Ten months after the onset of treatment, the patient feels good, clinical examination findings are normal, and no sign of evolutive cryptococcosis is noted.

Topics: Abscess; Amphotericin B; Animals; Antifungal Agents; Combined Modality Therapy; Cryptococcosis; Debridement; Diagnosis, Differential; Ducks; Environmental Exposure; Facial Injuries; Fluconazole; Graft Rejection; Granuloma; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Osteitis; Osteolysis; Parietal Bone; Postoperative Complications; Remission Induction; Seminoma; Skull Neoplasms; Subcutaneous Tissue; Testicular Neoplasms

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Diagnosis, Differential; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Liver Neoplasms; Male; Middle Aged; Thigh

Meningoradiculitis refers to combined involvement of meninges and nerve roots. The most frequent location is the lumbosacral region. Etiology is diverse, including inflammatory, infectious and neoplastic disorders. Meningoradiculitis is a rare form of involvement in cryptococcal infection. We describe a case of subacute lower limbs flaccid paresis diagnosed as lumbosacral meningoradiculitis in view of cerebrospinal fluid (CSF) inflammatory changes and typical enhancement on MRI of lumbar spine. Cryptococcus neoformans was isolated from CSF. Extensive screening yielded no immunodeficiencies.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Immunocompetence; Lumbosacral Region; Magnetic Resonance Imaging; Meningitis, Cryptococcal; Radiculopathy

In order to determine the potential role that various antifungal agents might have in the management of cryptococcosis in tropical areas, the in vitro susceptibility of Cryptococcus neoformans isolates from Africa ( n=52) and Cambodia ( n=110) to three antifungal agents (amphotericin B, fluconazole and voriconazole) were compared using the E-test method. The results of this study (i) confirm the value of the E-test for testing the in vitro susceptibility of C. neoformans towards voriconazole; (ii) provide the first evidence demonstrating good activity of amphotericin B, fluconazole and voriconazole against Cambodian isolates; and (iii) show there are differences in susceptibility between African and Asian C. neoformans isolates, with Cambodian isolates appearing less susceptible to the agents tested but with amphotericin B maintaining good activity.

Topics: Africa; Amphotericin B; Antifungal Agents; Cambodia; Cryptococcosis; Cryptococcus neoformans; Developing Countries; Drug Resistance, Fungal; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Pyrimidines; Risk Assessment; Sampling Studies; Triazoles; Voriconazole

In this study, 34 clinical cerebrospinal fluid isolates of Cryptococcus neoformans were serotyped, and their in vitro susceptibilities to amphotericin B, fluconazole, and voriconazole were analyzed. Of these 34 isolates, serotype A was found in 29 isolates and serotype B in the other five. The voriconazole geometric mean MIC was significantly lower than the amphotericin B/antibiotic medium 3 geometric mean MIC (P < 0.0001 at both 48 and 72 h), as well as the fluconazole geometric mean MIC (P < 0.0001 at both 48 and 72 h). Of the three antifungal agents, only fluconazole, with geometric mean MICs at both 48 and 72 h, showed significant difference between the serotypes A and B of C. neoformans.

Topics: Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Humans; Microbial Sensitivity Tests; Pyrimidines; Serotyping; Taiwan; Triazoles; Voriconazole

We report a case of a primary pulmonary infection due to Cryptococcus neoformans developed in a 40 Year old immunocompetent and HIV negative man. Radiologic findings consisted in diffuse, bilateral reticular and nodular opacities. Bronchoscopy was normal and bronchoalveolar lavage showed numerous macrophages without associated pathogens. A thoracovideoscopy with an open lung biopsy showed numerous cryptococci, free in the alveoli or located within the macrophages. They were associated with an inflammatory infiltrate in the interalveolar spaces, predominantly composed of mononuclear cells. Ultrastructural study showed yeasts with numerous intracytoplasmic organites, a nucleus, a wall and a thick capsule. Pulmonary cryptococcosis is rare in immunocompetent hosts and can be difficult to diagnose since clinicoradiologic features observed in this cryptococcal infection mimic other infectious or neoplastic diseases.

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Humans; Immunocompetence; Lung; Lung Diseases, Fungal; Male; Radiography; Treatment Outcome

Eighteen cases of disease caused by the saprophytic fungi Cryptococcus neoformans and Cryptococcus bacillisporus are described from the Northern Territory of Australia. The majority of infections were with Cryptococcus bacillisporus and in the rural Aboriginal population, often causing pulmonary mass lesions.

Topics: Amphotericin B; Antifungal Agents; Australia; Cryptococcosis; Cryptococcus; Humans; Meningitis, Cryptococcal; Native Hawaiian or Other Pacific Islander; Tropical Climate

To investigate the effects of posaconazole (POS) and amphotericin B (AMB) combination therapy in cryptococcal infection, we established an experimental model of systemic cryptococcosis in CD1 mice by intravenous injection of three distinct clinical isolates of Cryptococcus neoformans. Therapy was started 24 h after the infection and continued for 10 consecutive days. POS was given at 3 and 10 mg/kg of body weight/day, while AMB was given at 0.3 mg/kg/day. Combination therapy consisted of POS given at a low (combo 3) or at a high (combo 10) dose plus AMB. Survival studies showed that combo 3 was significantly more effective than POS at 3 mg/kg for two isolates tested (P value, < or = 0.001), while combo 10 was significantly more effective than POS at 10 mg/kg for all three isolates (P values ranging from <0.001 to 0.005). However, neither combination regimen was more effective than AMB alone. For two isolates, combination therapy was significantly more effective than each single drug at reducing the fungal burden in the brain (P values ranging from 0.001 to 0.015) but not in the lungs. This study demonstrates that the major impact of POS and AMB combination therapy is on brain fungal burden rather than on survival.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antifungal Agents; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Progression; Drug Therapy, Combination; Humans; Lung; Male; Mice; Survival Analysis; Triazoles

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Lung Diseases, Fungal; Male; Middle Aged; Radiography, Thoracic

To describe a case of a scleral ulceration caused by Cryptococcus albidus in a patient with acquired immune deficiency syndrome (AIDS).. Interventional case report. A 16-year-old girl with AIDS was admitted to the hospital with a 1-week history of cough, fever, and sudden onset of a painless scleral lesion on her left eye. Culture of the lesion revealed the fungus Crypotococcus albidus.. The patient was treated with topical amphotericin B and systemic itraconazole, and she recovered fully over 4 weeks without sequelae.. Cryptococcus albidus rarely causes disease in humans. It should be considered as a potential cause of ocular and systemic disease in patients with AIDS.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Eye Infections, Fungal; Female; Humans; Itraconazole; Scleral Diseases; Ulcer

We report a 71/2-year-boy with disseminated systemic cryptococcosis. Although other species have been incriminated, this appears to be the first report of Cryptococcus humicolus. The child was HIV negative. He was treated with amphotericin B and fluconazole with intensive supportive care. The child responded after 6 weeks and is now on maintenance fluconazole therapy.

Topics: Amphotericin B; Antifungal Agents; Child; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Fluconazole; Humans; Male

A 20-year-old Welsh Mountain Pony (212 kg) mare was initially presented for a chronic cough, fever, weight loss and low grade abdominal pain. She later developed dyspnoea, tachypnoea and exercise intolerance. The presence of multiple masses (up to 17 cm diameter) in the pulmonary parenchyma was established using lateral thoracic radiography and transthoracic ultrasonography. Encapsulated, budding yeasts were observed in smears made from transtracheal washings and needle aspirates of the pulmonary lesions. Cryptococcus gattii (synonym: Cryptococcus neoformans variety gattii; Cryptococcus bacillisporus) was cultured from the transtracheal washings and aspirates of the lung masses. The pony was successfully treated using daily intravenous infusions of amphotericin B (typically 0.5 mg/kg in 1 L 5% dextrose in water over 1 h, following premedication with 50 mg flunixin intravenously) over a 1 month period, until a cumulative dose of 3 g had been administered. Treatment was considered to be successful on the basis of progressive improvement in clinical signs, reduction in the size of pulmonary cryptococcomas, 48 kg weight gain and a reduction in the cryptococcal antigen titre from 4096 to 256, 1 year after cessation of treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Cough; Cryptococcosis; Diagnosis, Differential; Female; Horse Diseases; Horses; Infusions, Intravenous; Pneumonia; Radiography; Ultrasonography

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Cryptococcosis; Cryptococcus neoformans; Granuloma; Humans; Immunocompetence; Lymph Nodes; Lymphadenitis; Male; Staining and Labeling; Treatment Outcome

Cryptococcus neoformans is the cause of the most common life-threatening fungal infection in patients with AIDS. Thirty strains of C. neoformans were collected from inpatients and typied evaluating activity, morphotyping, serotyping, chemosensitivity and adhesivity. Cryptococcus neoformans strains showed different aspectotype profile, the sole presence of serotypes A and D, good susceptibility to azoles and Amphotericin B. Phenotypic epidemiologic markers can be used: characterization of clinical strains excludes a common source.

Topics: Adult; Agglutination Tests; Amphotericin B; Antifungal Agents; Azoles; Cell Adhesion; Cryptococcosis; Cryptococcus neoformans; Endopeptidases; Female; Flucytosine; Humans; Italy; Male; Microbial Sensitivity Tests; Middle Aged; Monophenol Monooxygenase; Phenotype; Urease

Ambisome (L-Amb) was used to treat nine cases of meningitis or menigoencephalitis by Cryptococcus neoformans and 28 cases of other deep fungal infections. A retrospective study on conventional amphotericin B (C-Amb) was performed as the control. A series of indices was observed including curative effect, fungal clearance rate, course of treatment, daily dose, cumulative dose and adverse effects. Nine cases of cryptococcal meningitis or menigoencephalitis treated with Ambisome were clinically cured with an effective rate of 100%, within a mean course of 50 days, which was shorter than that of C-Amb, by a mean cumulative dose of 1807.2 mg, which was not statistically significant in comparison with C-Amb. Fungal clearance rate on the second month of treatment was 89% with Ambisome, which was higher than that of C-Amb. Twenty-eight cases of other deep fungal infections treated with Ambisome were clinically cured with an effective rate of 92%, within a mean course of 19.3 days, by a mean cumulative dose of 907.5 mg, and fungal clearance rate on the second and third month was 75 and 92%, respectively. The adverse effects by Ambisome decreased evidently compared with those by C-Amb.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Child, Preschool; China; Cryptococcosis; Cryptococcus neoformans; Drug Delivery Systems; Female; Humans; Liposomes; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Cladribine; Cryptococcosis; Fluconazole; Humans; Leukemia, Hairy Cell; Male; Middle Aged; Remission Induction

A case of disseminated cryptococcosis caused by Cryptococcus neoformans var. grubii is presented in a male diabetic who had AIDS. The diagnosis was based upon the isolation and identification of the aetiological agent from a lymph-node biopsy, cerebrospinal fluid and sputum. The isolate formed spherical, encapsulated yeast cells, produced cherry-brown colonies on niger-seed agar, grew on canavanine-glycine-bromothymol blue (CGB) medium, changing its colour from greenish yellow to blue, and hydrolysed urea weakly in the presence of 100 microM EDTA. The strain was unable to assimilate D-proline and, serologically, it was untypable. The identity of the isolate as C. neoformans var. grubii, serotype A, possessing a mating-type allele A alpha, was confirmed by crossing with standard laboratory test strains and by performing PCR with the mating-type alpha allele-specific primer of the STE12 gene and with serotype (A and D)- and mating type (a and alpha)-specific primers of the STE20 gene. To the best of our knowledge, this is the first report of disseminated cryptococcosis in an AIDS patient caused by a canavanine-resistant strain of C. neoformans var. grubii, serotype A, possessing mating type allele A alpha; the strain is probably a hybrid. The report suggests that, in the absence of a clear-cut serotyping result, a positive CGB reaction alone is not sufficient for intervarietal discrimination and additional confirmatory evidence is required.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Canavanine; Cryptococcosis; Cryptococcus neoformans; Diabetes Mellitus; Drug Resistance, Fungal; Fatal Outcome; Fluconazole; Humans; Male; Middle Aged

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Immunosuppressive Agents; Incidence; Longitudinal Studies; Male; Middle Aged; Transplants

Topics: Adult; Amphotericin B; Antifungal Agents; Behcet Syndrome; Cryptococcosis; Cryptococcus neoformans; Glucocorticoids; Humans; Leg Ulcer; Male; Prednisone

Cryptococcus neoformans, an opportunistic fungus, may cause cutaneous disease by dissemination from primary lung infection or, more rarely, by direct cutaneous inoculation. Cellulitis in an immunocompromised host who does not respond to conventional antibacterial therapy should alert the physician to consider other diagnoses, including cryptococcal skin infection.

Topics: Adult; Amphotericin B; Antifungal Agents; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Female; Flucytosine; Humans; Renal Dialysis

Topics: Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Birefringence; Cellulitis; Cryptococcosis; Cryptococcus; Fluconazole; Humans; Male; Middle Aged; Pemphigus; Prednisone; Skin

Disseminated cryptococcosis mainly occurs in patients with cell-mediated immunity disorders. A case of disseminated cryptococcosis, in a patient with pituitary Cushing's disease, is reported. Cultures of blood, cerebrospinal fluid (CSF) and aspirates of a skin lesion all grew Cryptococcus neoformans. Despite antifungal treatment, with amphotericin-B, the patient died within 3 weeks.

Topics: Amphotericin B; Antifungal Agents; Brain; Cryptococcosis; Cushing Syndrome; Fatal Outcome; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Pituitary Diseases; Radiography

Cryptococcal necrotizing fasciitis that is localized to the lower extremities is very rare.. We describe a case of a renal transplant recipient who presented with necrotizing fasciitis of the legs caused by Cryptococcus neoformans, a fungus that is rarely associated with this disease.. This is a case report with literature review.. The patient was hospitalized, and the site of infection was debrided to the level of the periosteum. Cultures and histopathologic examination of biopsy material revealed an invasive deep-seated infection with a fungal organism that was consistent with C. neoformans. After 21 days on parenteral amphotericin B (Ambisome; Er-Kim Pharmaceuticals) treatment, the patient was switched to oral itraconazole (Itraspor; Janssen-Cilag Pharmaceuticals) 200 mg/day. He was discharged after 30 days of hospitalization with his wounds completely healed. He continued on oral fluconazole for a total course of 6 weeks.. Systemic fungal infections continue to be an important cause of morbidity and mortality in transplant recipients. The insidious nature and atypical manifestations of these infections often delay diagnosis and therapy. In immunosuppressed patients, persistent fever that does not respond to antibacterial therapy should alert the physician to the possibility of fungal infection.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Cryptococcosis; Debridement; Fasciitis, Necrotizing; Humans; Immunocompromised Host; Kidney Transplantation; Leg; Male; Middle Aged; Skin Transplantation; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Immunosuppressive Agents; Organ Transplantation

A 48-year-old man with a history of sarcoidosis was transferred to the Mayo Clinic for evaluation and management of progressive neurologic decline. Two years before admission, he was admitted to a local hospital with mental status changes accompanied by ataxia and severe headache. A diagnosis of pulmonary and central nervous system sarcoidosis was made based on computed tomography of the head, lumbar puncture, and chest radiography. A mediastinoscopy with lymph node biopsy exhibited noncaseating granulomas and negative stains for microorganisms. Prednisone therapy was initiated at 80 mg/day. Clinical improvement was apparent for 13 months during steroid therapy until the slow taper reached a dosage of 20 mg/day. At that time, the patient was readmitted to the local hospital with severe confusion and skin lesions. When intravenous methylprednisolone therapy for presumed central nervous system sarcoidosis did not improve the patient's mental status, he was transferred to the Mayo Clinic. Physical examination of the thighs revealed large, well-marginated, indurated, irregularly bordered, violaceous plaques and rare, umbilicated, satellite papules with central hemorrhagic crusts (Fig. 1A). Superficially ulcerated plaques with a similar appearance to the thigh lesions were coalescing around the lower legs (Fig. 1B). A skin biopsy specimen of the thigh demonstrated abundant numbers of encapsulated organisms and minimal inflammatory response (Fig. 2). Skin, blood, and cerebrospinal fluid cultures confirmed the presence of Cryptococcus neoformans. Amphotericin and flucytosine combination therapy was initiated, and steroid dosages were gradually tapered. A test for human immunodeficiency virus was negative. The patient was dismissed from hospital after a complicated 2-month course resulting in improved mental status but progression of the lower extremity ulcerations as a result of polymicrobial infection.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Male; Middle Aged; Opportunistic Infections; Sarcoidosis

A Cryptococcus neoformans strain from cutaneous lesions of a patient with thrombotic thrombocytopenia purpura was tested for in vitro susceptibility against seven conventional antifungal agents. The strain was susceptible to fluconazole, itraconazole, ketoconazole and miconazole but was resistant to 5-fluorocytosine (5-FC). Minimal inhibitory concentration (MIC) values obtained against amphotericin B and terbinafine were 1 and 4 microg ml(-1), respectively. The isolate belonged to serotype D. Few human cases of cryptococcosis have been reported over the last 50 years in Turkey. This is the first C. neoformans isolate in Turkey shown to have primary resistance to 5-FC. Primary resistance to flucytosine is rarely reported in C. neoformans and may be associated with treatment failure in some cases.

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Drug Resistance, Fungal; Flucytosine; Humans; Male; Purpura, Thrombotic Thrombocytopenic; Skin

In vitro susceptibility to the sordarin derivative GM 237354 and amphotericin B were tested in a total of 190 Cryptococcus neoformans clinical isolates from different geographical areas of Spain and South American countries. Minimal inhibitory concentrations (MICs) were obtained using the NCCLS reference microbroth dilution method and analysed according the serotypes of Cr. neoformans. The MICs for amphotericin B were lower than 1.0 microg ml(-1) (MIC90% 0.5 microg ml(-1) , MIC50% 0.125 microg ml(-1)) but five isolates showed MICs of 2.0 microg ml(-1) to GM 237354 (MIC90% 1.0 microg ml(-1), MIC50% 0.5 microg ml(-1)). Cryptococcus neoformans var. gattii serotype B, was significantly less susceptible than A and AD serotypes (P = 0.047 and P = 0.022, respectively).

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Indenes; Microbial Sensitivity Tests; Serotyping

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Humans; Prognosis

Cryptococcus neoformans is an important fungal pathogen in both immunocompromised and immunocompetent hosts. The mean annual incidence during 1994-1997 was 6.6 cases per million people per year in Australia, and 2.2 cases per million people per year in New Zealand. C. neoformans var. neoformans caused 85% of 312 episodes (98% of episodes in immunocompromised hosts) and C. neoformans var. gattii caused 15% (44% in immunocompetent hosts). The AIDS-specific incidence declined significantly over the 3 years. Mortality from cryptococcosis remains substantial. In trials involving small numbers of AIDS patients, liposomal amphotericin B (AmBisome) was found to be active against C. neoformans, with mycological response rates of 67-85%; however, maintenance therapy with an oral antifungal agent is required indefinitely. In a randomized study of patients with cryptococcal meningitis, AmBisome (4 mg/kg/day) produced mycological eradication in 73% of patients compared with 38% with conventional amphotericin. AmBisome resulted in significantly earlier sterilization of cerebrospinal fluid than conventional amphotericin (7-14 days versus 21 days) and was less nephrotoxic. The benefit of this reduced toxicity is denied to many patients because of an enormous cost barrier. In a survey of the practices of clinical mycologists in Australia, 11 experts responded to a questionnaire survey regarding the use of available lipid preparations. Their indications for use as initial therapy were mucormycosis (7/10), renal failure (7/10), Fusarium infection (2/10) and aspergillosis (2/10). Cryptococcosis, candidosis and febrile neutropenia were rarely regarded as an indication; failed therapy with conventional amphotericin was an indication to use AmBisome for 8/11 respondents. The majority believed that AmBisome was equivalent to conventional amphotericin, with amphotericin B lipid complex and AmBisome equivalent to each other in terms of efficacy. The main barrier to replacement of conventional amphotericin with lipid preparations was seen as an issue of cost.

Topics: Adult; Age Factors; Amphotericin B; Antifungal Agents; Australia; Child; Cryptococcosis; Female; Humans; Liposomes; Male; Middle Aged; Mycoses; New Zealand

We report on a case of cryptococcal intramedullary abscess, which occurred three years after a disseminated cryptococcosis and two years after a lymph node cryptococcal recurrence in a HIV-infected patient who exhibited a long-standing immune restoration. At the time of diagnosis, CD4(+) lymphocyte-count was 640x10(6)/l and HIV viral load was undetectable. Spinal involvement is rare during cryptococcosis of the central nervous system. As far as we are aware, there is only one case of proven intramedullary cryptococcal abscess reported in the literature and this case is then the second one. The significant and sustained increase in CD4 count following effective antiretroviral therapy was probably associated with only a partial immune restitution that did not allow to avoid the occurrence of the cryptococcal medullar abscess. Finally, this case raises the question of when to stop secondary prophylaxis of cryptococcal disease after increase in CD4 cell count under antiretroviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brain Abscess; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Flucytosine; Humans; Male

We have previously shown that gamma interferon (IFN-gamma) is a useful adjunct to therapy of experimental systemic cryptococcosis in normal mice. To better emulate AIDS patients, SCID mice were infected intravenously with Cryptococcus neoformans. Mice received no therapy, 3 mg of amphotericin B (AmB) per kg of body weight, or 10(5) U of IFN-gamma alone (prophylactically and therapeutically or only therapeutically) or with AmB. In the first experiment, >75% of the mice survived. Therapy with AmB alone was efficacious compared to no therapy in all organs. Both regimens of IFN-gamma alone were efficacious in the brain and lungs, and the combination of AmB and IFN-gamma showed significant synergy in the kidneys. AmB alone cured 40% of mice of infection, whereas the combination regimens cured >50% of the mice and 90% of the brain infections. In a second study, IFN-gamma again proved efficacious alone, and when given with AmB its efficacy was improved. Therapeutic IFN-gamma alone was effective only in the liver compared to no therapy, and the combination regimen, although highly effective, showed no significant synergy. In a third experiment, AmB alone or in combination with IFN-gamma prolonged survival compared to no therapy or IFN-gamma alone. The combination regimen showed significant synergy over AmB alone in the brain, liver, kidneys, and lungs. AmB alone cured no mice of infections in more than two organs, whereas AmB in combination with IFN-gamma cured 55% of infections in three or more organs. These results indicate that IFN-gamma has therapeutic efficacy in severely immunodeficient animals, especially in combination with AmB. Significant synergistic activity was noted in all organs except the spleen. Overall, IFN-gamma has utility as an adjunctive therapy against systemic cryptococcosis in the severely immunocompromised host.

Topics: Adjuvants, Immunologic; Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Disease Models, Animal; Drug Therapy, Combination; Interferon-gamma; Male; Mice; Mice, SCID; Recombinant Proteins; Treatment Outcome

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

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cryptococcosis; Fluconazole; Flucytosine; Histoplasmosis; Humans; Immunosuppression Therapy; Mycology; Mycoses; Neutropenia; Prognosis; Risk Factors; Travel

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Choroiditis; Coloring Agents; Cryptococcosis; Cryptococcus neoformans; Eye Infections, Fungal; Fatal Outcome; Fluorescein Angiography; Humans; Indocyanine Green; Male

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Chorioretinitis; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Multiple, Fungal; Fluconazole; Flucytosine; Humans; Itraconazole; Meningitis, Cryptococcal; Pneumonia; Prednisolone; Pyrimidines; Triazoles; Voriconazole

The first case of a cutaneous cryptococcosis associated with systemic erythematous lupus (SLE) diagnosed in our Mycology Reference Centre is presented: a 24-year-old female patient diagnosed with SLE, nephrotic syndrome, arterial hypertension, renal insufficiency due to glomerulonephritis type IV and cellulitis in the right thigh and gluteus. Cryptococcus neoformans was isolated by cutaneous biopsy and haemoculture. Cryptococcal antigen was detected in serum by the latex agglutination test. As the patient did not respond to fluconazol intravenous treatment, amphotericin B administration was performed. She died of acute renal insufficiency.

Topics: Adult; Agglutination Tests; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fatal Outcome; Female; Fluconazole; Fungemia; Humans; Injections, Intravenous; Lupus Erythematosus, Systemic; Renal Insufficiency

The in vitro activities of three antifungal drugs alone and in combination were evaluated against five isolates of Cryptococcus neoformans using time-kill curves (TKC). The isolates were from AIDS patients who had either died or had failed to show a clinical response during amphotericin B (AMB) treatment. AMB, fluconazole (FCZ) and flucytosine (5FC), and combinations of the drugs (AMB plus 5FC, AMB plus rifampicin (RIF) and FCZ plus 5FC), were evaluated. With all five isolates AMB did not show fungicidal activity; instead, a persistent or tolerant effect was observed. Combinations of AMB plus 5FC and AMB plus RIF showed a clear synergic effect, except for one isolate tested with AMB plus RIF. In contrast, the FCZ plus 5FC combination did not inhibit growth of any isolate.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Interactions; Drug Resistance, Microbial; Fluconazole; Flucytosine; Humans; Leprostatic Agents; Rifampin; Time Factors

One hundred years after introduction of the Eucalyptus tree to Taiwan, a predominantly subtropical island, we analyzed clinical and microbiological data of 59 patients with Cryptococcus neoformans infection hospitalized at National Taiwan University Hospital during 1982 to 1997. There were 38 (64.4%) cases of cryptococcosis caused by the var. neoformans and 21 (35.6%) caused by the var. gattii. Thirty-three patients (55.9%) had impaired T cell function, which included 12 patients with acquired immunodeficiency syndrome (AIDS). Eleven of the 12 patients with AIDS were diagnosed after 1995, and 11 cases were caused by var. neoformans. Minimum inhibitory concentrations (MICs) determined by the NCCLS broth microdilution method using antibiotic medium 3 improved the discrimination of in vitro susceptibility against amphotericin B and demonstrated that var. gattii isolates were less susceptible (geometric means 0.25 microg/ml versus 0.64 microg/ml, P < 0.001). In addition, a higher proportion of var. gattii were less susceptible to flucytosine as compared with var. neoformans (35.0% versus 64.9%, P = 0.030). There was no seasonal clustering for isolation of var. neoformans, though infections caused by var. gattii peaked in July and August. Compared with the first study of cryptococcosis (1957-1972) at NTUH, this study demonstrated the increase in immunocompromised and elderly patients, as well as a higher proportion of Cryptococcus isolated from blood or bone marrow. Facing the increasing adaptive plantation of Eucalyptus in Taiwan, the importance of field study regarding the role of Eucalyptus plantations in Taiwan and occurrence of cryptococcosis in human beings cannot be over-emphasized.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; Humans; Immunocompromised Host; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Seasons; Taiwan

Melanin-specific reagents revealed melanin in cryptococcal cell walls from human brain tissue, and fungal-cell melanin "ghosts" were recovered from infected tissue. The results indicate that Cryptococcus neoformans melanises during human infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Cryptococcus neoformans; Dopamine Antagonists; Humans; Melanins; Rodentia; Trifluoperazine

Infection with Cryptococcus neoformans is an increasing problem in immunocompromised patients, particularly those with acquired immune deficiency syndrome (AIDS). Amphotericin B and fluconazole are currently acceptable therapies for cryptococcal meningitis; however, their effects remain suboptimal and recurrence or treatment failure is still a problem. Antifungal susceptibility testing may be an important tool for guiding therapy, but for C. neoformans, a reliable method is still not available. This retrospective study evaluated minimal inhibitory concentration (MIC) for amphotericin B and fluconazole, and minimal fungicidal concentration (MFC) and timed-kill curves for amphotericin B against 16 clinical isolates of C. neoformans obtained from AIDS patients with cryptococcal meningitis. No correlation between clinical outcome and MIC was observed for amphotericin B. In selected cases, the MFC seemed to be a better predictor of outcome than MIC. In this study, amphotericin B timed-kill curves appeared to show a correlation with clinical outcome of the 16 patients with AIDS-associated cryptococcal meningitis. These in vitro tests must be further evaluated in prospective studies to confirm their potential usefulness for guiding cryptococcal meningitis therapy.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Microbial Sensitivity Tests; Recurrence; Retrospective Studies; Time Factors

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequenti

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Therapy, Combination; Fluconazole; Humans; Itraconazole; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Triazoles

The possible enhancement, using immunotherapy with interferon-gamma (IFN-gamma), combined with conventional antifungal therapy, was studied in a murine model of systemic cryptococcosis. Four weeks after intravenous challenge, infection was quantified in brains and livers of survivors. Groups received IFN-gamma every other day beginning 7 days before (prophylaxis), or after infection (14 doses), or amphotericin B post-infection, or combinations of these regimens. IFN-gamma alone was modestly effective, but impressively and significantly potentiated amphotericin in reducing infection in the most important site of infection, the brain. The efficacy was seen after lethal and non-lethal challenges, and when IFN-gamma was given by the intravenous or subcutaneous routes. In non-lethal infection, only the combination amphotericin-IFN-gamma resulted in sterilization of the central nervous system. Potentiation of fluconazole was less impressive. Adding prophylactic IFN-gamma doses to IFN-gamma therapy did not consistently enhance the therapeutic effect. These results suggest IFN-gamma may have a role in potentiating conventional antifungal therapy of cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Fluconazole; Humans; Interferon-gamma; Liver; Male; Mice; Mice, Inbred BALB C

Cryptococcal meningitis (CM) is common in the immunocompromised (especially due to AIDS), but also occurs in immunocompetent subjects. CM can complicate cryptococcal pneumonia (CP) not only in the immunocompromised but also in the immunocompetent. We describe a healthy 26-year-old man who developed a prolonged lung infection. Diagnosis of cryptococcal pneumonia was established from bronchoscopic washings. He recovered spontaneously, so no antifungal treatment was given. 4 months later he was admitted with cryptococcal meningitis and was treated successfully with amphotericin B. An extensive immunologic study revealed no abnormalities. Since CM can complicate cryptococcal pneumonia, it is recommended that patients with CP be followed, even if recovery is apparently complete.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Humans; Immunocompetence; Lung Diseases, Fungal; Male; Meningitis, Cryptococcal; Pneumonia; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Eye Infections, Fungal; Eyelid Diseases; Flucytosine; Humans; Male; Skin Diseases, Bacterial

The objectives of this study were to analyze the changes in the incidence of cryptococcal disease in the last 10 years (1987-1997) and to assess the factors of poor prognosis in HIV-1 infected patients.. Clinical records of HIV-1 infected patients diagnosed with cryptococcal infection from June 1987 to December 1997 at Hospital Clinic i Provincial in Barcelona, Spain, were examined. An univariate and multivariate analysis of the predictors of poor outcome was performed.. Sixty clinical records were analyzed. The number of cases per 100 exposed patients per year decreased from 1991 to 1993 and, afterwards, decreased again from 1996. Fifty patients had a resolution of clinical symptoms, 17 out of this 50 patients (34%) had a relapse. Factors associated with a higher risk of relapse were a positive blood culture and cryptococcal antigen title in cerebrospinal fluid above 1/1.024.. The decrease in the number of cases of cryptococcal infection coincides with the broad use of triazole antifungal drugs for oral candidiasis (1990-1991) and, afterwards, with the initiation of highly active antiretroviral therapy (1996). The best predictors of relapse are a positive blood cryptococcal culture and a high titter of cryptococcal antigen.

Topics: Acute Disease; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Analysis of Variance; Antifungal Agents; Cohort Studies; Cryptococcosis; Data Interpretation, Statistical; Female; Fluconazole; Flucytosine; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Recurrence; Spain; Treatment Outcome

A rare case of cryptococcosis of sixth thoracic vertebra (T6) along with pulmonary involvement in an old diabetic patient is presented. The infection resulted in lytic lesion of T6 vertebra and girdle pain. A computerized tomographic (CT) guided fine-needle aspiration biopsy (FNAB) cytology was performed, which showed encapsulated fungal spores of Cryptococcus neoformans with granulomatous reaction, later confirmed by fungal culture.

Topics: Aged; Amphotericin B; Antifungal Agents; Antitubercular Agents; Biopsy, Needle; Cryptococcosis; Diagnosis, Differential; Humans; Spinal Diseases; Thoracic Vertebrae; Tomography, X-Ray Computed; Tuberculosis

To review a serie of patients with cryptococcal meningitis and immunodeficiency syndrome (AIDS) treated in our hospital in the last two years.. Retrospective study of 25 patients infected with the human immunodeficiency virus (HIV) and affected by Cryptococcus neoformans meningitis. The factors analysed were epidemiological data, clinical manifestations, biochemical and microbiological characteristics of cerebrospinal fluid (CSF), radiological abnormalities, treatment, adverse reactions and outcomes.. Eighty-four percent of patients had less than 200 CD4/microliter. Cryptococcal infection was the AIDS defining illness in 24% of cases. Patients typically presented with neurologic symptoms such as: headache (88%), fever (68%) and somnolence (68%); 20% presented seizures and 28% focal deficits. There were no CSF biochemical alterations in 25% of them. CSF culture and indian ink stain were positive in 76%. CSF cryptococcal antigen test was positive in 68% of the cases. TC showed abnormalities in 48%. CSF of all patients treated with amphotericin B (AB) plus flucytosine (5FC) whose CSF culture was monitored became negative in the first two weeks, meanwhile those treated only with AB or fluconazol had negative control culture in 60% and 50% respectively. Six patients died within the initial 10 weeks. Death was due to bacterian sepsis in 3 patients and high intracranial pressure was the cause in 2 cases. One happened before treatment was administered.. It's essential to consider the possibility of cryptococcal meningitis in patients infected with HIV and any compatible symptom regardless of CSF biochemical results and immunodepression level (CD4). Although our study was non randomized and so we can't propose a therapeutical schedule based on it, we can say that patients treated with AB plus 5FC showed an earlier conversion from positive to negative CSF cultures without more adverse reactions.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Flucytosine; HIV Seropositivity; Humans; Male; Meningitis, Bacterial; Middle Aged; Retrospective Studies

New, stable, highly water-soluble, nontoxic polysaccharide conjugates of amphotericin B (AmB) are described. AmB was conjugated by a Schiff-base reaction with oxidized arabinogalactan (AG). AG is a highly branched natural polysaccharide with unusual water solubility (70% in water). A high yield of active AmB was obtained with the conjugates which were similarly highly water soluble and which could be appropriately formulated for injection. They showed comparable MICs for Candida albicans and Cryptococcus neoformans (MICs, 0.1 to 0.2 microg/ml). The reduced AmB conjugate, which was synthesized at pH 11 for 48 h at 37 degrees C, was nonhemolytic and was much safer than conventional micellar AmB-deoxycholate. It was the least toxic AmB-AG conjugate among those tested with mice (maximal tolerated dose, 50 mg/kg of body weight), and histopathology indicated no damage to the liver or kidneys. This conjugate, similarly to the liposomal formulation (AmBisome), was more effective than AmB-deoxycholate in prolonging survival. It was more effective than both the liposomal and the deoxycholate formulations in eradicating yeast cells from target organs. The overall results suggest that after further development of the AmB-AG conjugate, it may be a potent agent in the treatment of fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Erythrocytes; Galactans; Hemolysis; Injections, Intravenous; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Sheep; Solubility; Water

Cryptococcal infection uncommonly presents with pulmonary manifestations and even more rarely so as massive bilateral effusions. Pleural involvement is usually associated with underlying pulmonary parenchymal lesions and is unusual while on antifungal therapy. We report a patient with cryptococcal meningitis who, while on intravenous 5-flucytosine and amphotericin B, developed life-threatening bilateral massive pleural effusions with evidence of spontaneous resolution, consistent with prior hypothesis of antigenic stimulation as the cause of pleural involvement.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Flucytosine; Humans; Meningitis, Cryptococcal; Pleural Effusion

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Microbial; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Immunocompetence; Male; Meningitis

We present a case of recovery from fulminant hepatic failure secondary to high serum levels of fluconazole precipitated by amphotericin B induced renal dysfunction. Fluconazole dose adjustment or alternative antifungal treatment should be considered in patients with impaired renal function.

Topics: Amphotericin B; Antifungal Agents; Chemical and Drug Induced Liver Injury; Cryptococcosis; Female; Fluconazole; Humans; Kidney; Liver Failure; Middle Aged

We have treated seven patients with cryptococcal spondylitis. Five presented with a neurological deficit and one was HIV-positive. Amphotericin-B and 5-flucytosine were used in five patients and ketoconazole was given orally in the remaining two. Three patients made a complete neurological recovery. Since these lesions mimic spinal tuberculosis, which is commonly seen in our environment, we draw attention to the importance of obtaining a tissue diagnosis.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Bone Transplantation; Child; Combined Modality Therapy; Cryptococcosis; Decompression, Surgical; Diagnosis, Differential; Female; Flucytosine; Humans; Ketoconazole; Male; Spondylitis

Occurrence of cryptococcal endophthalmitis is rare and commonly is associated with widespread disseminated diseases. The authors report here a well-documented case of endogenous cryptococcal endophthalmitis without the preceding meningeal infection.. A 45-year-old female with a history of long-term use of systemic corticosteroid and cytotoxic drugs for systemic lupus erythematosus suffered from progressive visual loss in her left eye over 1 month. Large exudative retinal detachment and severe vitreous infiltration were observed.. Histopathologic study of the retinal biopsy specimen established the diagnosis of cryptococcal endophthalmitis. Subsequent positive histopathologic study of the aspiration vitreous smear and epiretinal membrane confirmed the recurrence and persistence of the disease over 4 months after the initial presentation. Systemic amphotericin B-fluconazole and two doses of intravitreous amphotericin B injection eliminated the infection successfully.. The authors report here a well-documented case of cryptococcal endophthalmitis and present the serial clinical and histopathologic pictures. The importance of retinal biopsy in diagnosis and the combined form of antifungal treatment also are shown.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Fluorescein Angiography; Humans; Middle Aged; Retina; Vitreous Body

We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses. Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever. The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs. Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks). Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination. Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection. Death usually occurred early in patients who presented late. Once patients responded to therapy, mortality was usually avoided. The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures. Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Follow-Up Studies; Humans; Lung Diseases, Fungal; Malaysia; Male; Meningitis, Cryptococcal; Middle Aged

Three lipid-based formulations of amphotericin B have been approved for use in various countries. The aim of this study was to compare Amphotec (ABCD; Sequus), AmBisome (AmBi; Nexstar), Abelcet (ABLC; The Liposome Co.), and conventional deoxycholate amphotericin B (Fungizone; Bristol Meyers Squibb) for the treatment of experimental systemic cryptococcosis. A model was established in 10-week-old female CD-1 mice by intravenous (i.v.) injection of 6.25 x 10(5) viable Cryptococcus neoformans yeast cells. Therapy began 4 days later, with i.v. administration three times per week for 2 weeks. Mice received either no treatment, 1 mg of Fungizone per kg of body weight, or 1, 5, or 10 mg of ABCD, AmBi, or ABLC per kg. Ninety percent of control mice died between days 15 and 34. All treatment regimens except ABLC at 1 mg/kg prolonged survival compared with no treatment (P < 0.01 to 0.001). All mice receiving 5 or 10 mg of ABCD or AmBi per kg and 90% of mice given 10 mg of ABLC per kg survived, whereas < or =50% of those given other treatment regimens survived. Fungizone was the least effective of the four formulations, with 5 or 10 mg of ABCD, AmBi, or ABLC per kg resulting in a significantly better outcome than Fungizone (P < 0.001). Among the three formulations, ABCD and AmBi were equally effective, both being better than ABLC at equal 5- or 10-mg/kg doses (P < 0.001). Comparison of residual infectious burdens in various organs showed that each drug had some dose-responsive efficacy in three or more organs at escalating doses. In the brain, ABCD or AmBi at 5 or 10 mg/kg or ABLC at 10 mg/kg was more effective than Fungizone at 1 mg/kg or no treatment, while ABCD or AmBi at 1 mg/kg was as effective as ABLC at 10 mg/kg. Similar results were obtained for the kidneys and lungs. In the spleen, ABCD at 10 mg/kg cured all mice of infection and was superior to all other regimens. In the liver, AmBi at 5 mg/kg was superior to an equal dose of ABCD or ABLC. Overall, the efficacies of ABCD and AmBi were equal to that of Fungizone at 1 mg/kg and were about 10-fold better than that of ABLC, particularly in the brain; a comparative rank order of efficacies was ABCD approximately equal to AmBi > ABLC >> Fungizone. This is the first study that compared all four amphotericin B formulations.

Topics: Amphotericin B; Animals; Antifungal Agents; Colony-Forming Units Assay; Cryptococcosis; Female; Injections, Intravenous; Lipids; Mice; Survival; Time Factors

We report two cases of cryptococcosis in patients with Waldenstrom's macroglobulinaemia and chronic lymphocytic leukaemia that responded to prolonged therapy with systemic amphotericin and flucytosine. Cryptococcosis, although more common in those with impaired cell mediated immunity, should also be considered as a complication in patients with impaired antibody responses.

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Opportunistic Infections; Waldenstrom Macroglobulinemia

The activity of fluconazole and amphotericin B against three isolates of Cryptococcus neoformans was evaluated, with fluconazole and amphotericin B MICs of 2.0-4.0 mg/L and 1.0 mg/L respectively, using time-kill curve methods. Fluconazole was fungistatic against all isolates tested (<99.9% decrease in cfu from initial inoculum). The fungistatic activity of fluconazole was not enhanced by increasing the concentration of antifungal in solution. In contrast, amphotericin B was markedly fungicidal (> or = 99.9% decrease in cfu from initial inoculum). Both the rate and the extent of amphotericin B activity were enhanced when drug concentration was increased.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Culture Media, Conditioned; Dose-Response Relationship, Drug; Fluconazole; Humans; Microbial Sensitivity Tests; Species Specificity; Time Factors

Meningitis is often associated with hyponatremia due to inappropriate secretion of antidiuretic hormone, and diabetes insipidus is associated with bacterial meningitis. This article describes a patient with acquired immunodeficiency syndrome who experienced recurrent episodes of central diabetes insipidus in association with recurrent fungal meningitis. Desmopressin was effective in controlling the polyuria until the episodes of meningitis resolved.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypoglycemic Agents; Male; Meningitis, Fungal; Recurrence

Topics: Adult; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Choroiditis; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Eye Enucleation; Eye Infections, Fungal; Fluconazole; Humans; Kidney Transplantation; Male; Meningitis, Cryptococcal; Recurrence; Vitrectomy; Vitreous Body

In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Liposomes; Mice; Microbial Sensitivity Tests

A 52-year-old woman with a seven-year history of rheumatoid arthritis (RA) was transferred to our department with chronic renal failure to undergo hemodialysis. She had been treated with prednisolone for a long time, and had renal amyloidosis secondary to RA. During her hospitalization, a left pleural effusion developed. Pleural fluid cultured positive for Cryptococcus neoformans (CN), and the CN antigen was detected in both pleural fluid and serum. Chest computerized tomography revealed an infiltrate shadow in the left lower lung field suggestive of CN infection. This was successfully treated with anti-fungal agents. Pleural effusion is an unusual manifestation of pulmonary cryptococcosis. We should consider a diagnosis of CN infection when pleural effusion is observed in compromised patients such as those receiving a long-term corticosteroid treatment.

Topics: Amphotericin B; Amyloidosis; Anti-Inflammatory Agents; Antifungal Agents; Arthritis, Rheumatoid; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Kidney Failure, Chronic; Lung Diseases, Fungal; Middle Aged; Pleural Effusion; Prednisolone

We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Bone Marrow; Child, Preschool; Cryptococcosis; Drug Therapy, Combination; Fatal Outcome; Female; Fluconazole; Flucytosine; Humans; Liver; Lung; Lymph Nodes; T-Lymphocytopenia, Idiopathic CD4-Positive

Topics: Amphotericin B; Animals; Anti-Infective Agents; Antifungal Agents; Cryptococcosis; Enrofloxacin; Fluoroquinolones; Ketoconazole; Lizards; Quinolones

Although reliable detection of resistance in vitro is critical to the overall performance of any susceptibility testing method, the recently released National Committee for Clinical Laboratory Standards M27-A methodology for susceptibility testing of yeasts discriminates poorly between resistant and susceptible isolates of Candida spp. We have previously shown that both substitution of antibiotic medium 3 for RPMI 1640 medium in the microdilution variant of the M27-A method and use of the E-test agar diffusion methodology permit detection of amphotericin B-resistant Candida isolates. To determine the relevance of these observations to Cryptococcus neoformans, we have evaluated the performances of both the M27-A and the E-test methodologies with this yeast using three different media (RPMI 1640 medium, antibiotic medium 3, and yeast nitrogen base). As with Candida, we found that only antibiotic medium 3 permitted consistent detection of resistant isolates when testing was performed in broth by the M27-A method. When testing was performed by the E-test agar diffusion method, both RPMI 1640 medium and antibiotic medium 3 agar permitted ready detection of the resistant isolates. Reading of the results after 48 h of incubation was required for testing in broth by the M27-A method, while the MIC could be determined after either 48 or 72 h when the agar diffusion method was used.

Topics: Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus neoformans; Culture Media; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests

In this report, we present two cases of simultaneous infection with Blastomyces dermatitidis and Cryptococcus neoformans. In both cases, fungi were isolated from the lungs. The clinical manifestations were not suggestive of infection with two fungi. One patient was receiving immunosuppressive therapy and another was otherwise immunocompetent. A review of the literature failed to uncover any reports of co-infection with these two fungal pathogens. We discuss possible mechanisms for the isolation of both pathogens.

Topics: Aged; Amphotericin B; Antifungal Agents; Blastomyces; Blastomycosis; Cryptococcosis; Cryptococcus neoformans; Humans; Immunocompromised Host; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged

Heat-induced 'superaggregation' of deoxycholate-amphotericin B (AmB-DOC, Fungizone) was shown previously to reduce the in-vitro toxicity of this antifungal agent. We compared AmB-DOC with the formulation obtained by heating the commercial form (Fungizone, Bristol Myers Squibb, Paris, France) for 20 min at 70 degrees C, in the treatment of murine infections. An improvement of antifungal activity was obtained with heated AmB-DOC formulations due to a lower toxicity which allowed the administration of higher drug doses than those achievable with the commercial preparation. Single intravenous injections of heated AmB-DOC solutions were demonstrated to be two-fold less toxic than unheated ones to healthy mice. For mice infected with Candida albicans, the maximum tolerated dose was higher with heated than with unheated AmB-DOC solutions. In the model of murine candidiasis, following a single dose of heated AmB-DOC 0.5 mg/kg, 85% of mice survived for 3 weeks, whereas at this dose the immediate toxicity of the standard formulation in infected mice restricted the therapeutic efficacy to 25% survival. Both formulations were equally effective in increasing the survival time for murine cryptococcal pneumonia and meningoencephalitis. Injection of heated AmB-DOC solutions at a dose two-fold higher than the maximal tolerated dose observed with the unheated preparation (1.2 mg/kg) increased the survival time by a factor of 1.4 in cryptococcal meningoencephalitis. These results indicate that mild heat treatment of AmB-DOC solutions could provide a simple and economical method to improve the therapeutic index of this antifungal agent by reducing its toxicity on mammalian cells.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Chemistry, Pharmaceutical; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Hot Temperature; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mycoses

We report the first case of Cryptococcus laurentii meningitis and a rare case of Cryptococcus albidus cryptococcaemia in AIDS patients. Both infections were treated with amphotericin B and flucytosine. The C. laurentii meningitis was controlled after 2 weeks of treatment with no evidence of infection 20 months later. The patient with C. albidus cryptococcaemia, despite the amphotericin B/flucytosine combination therapy, died on the 14th day of treatment. The minimum inhibitory concentrations (MICs) for C. laurentii, as determined by Etest on RPMI 1640 agar, were 0.25 microg ml(-1) of amphotericin B, 1.25 microg ml(-1) flucytosine, 4 microg ml(-1) fluconazole, 0.50 microg ml(-1) itraconazole and 1.0 microg ml(-1) of ketoconazole. The MIC of amphotericin B for C. albidus was 0.5 microg ml(-1), flucytosine 1.25 microg ml(-1), fluzonazole 4 microg ml(-1), itraconazole 0.5 microg ml(-1) and ketonazole 0.25 microg ml(-1). The agreement of the amphotericin B MIC values obtained in antibiotic medium 3 by the broth microdilution method, with those obtained on casitone medium by Etest, was within a two-dilution range for both isolates. C. laurentii may cause meningitis and may also involve the lungs in AIDS patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Drug Therapy, Combination; Fatal Outcome; Female; Flucytosine; Humans; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged

Topics: Aged; Amphotericin B; Antifungal Agents; Cellulitis; Cryptococcosis; Dermatomycoses; Female; Fluconazole; Flucytosine; Humans; Immunocompetence; Itraconazole; Leg Dermatoses

The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.

Topics: Amphotericin B; Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Kidney; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses

Eleven isolates of Cryptococcus neoformans were investigated to determine the biochemical basis of their tolerance to fluconazole. The MICs of fluconazole for three isolates with low-level resistance were 3- to 6-fold higher than those for sensitive isolates, while the MICs for four isolates with high-level resistance were 100- to 200-fold higher than those for sensitive isolates. The level of ergosterol present in the isolates varied, and those which had relatively low levels of ergosterol were resistant to amphotericin B. Changes in the affinity of the target enzyme (sterol 14alpha-demethylase) and decreases in the cellular content of fluconazole seemed to be responsible for the resistance in isolates with low-level and high-level resistance, respectively.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Cytochrome P-450 Enzyme Inhibitors; Drug Resistance; Fluconazole; Microbial Sensitivity Tests; Oxidoreductases; Sterol 14-Demethylase; Sterols

The case of a 77-year-old man in whom a large digital ulcer with undermined edges was due to cutaneous infection by Cryptococcus neoformans variety neoformans serotype D, probably following direct inoculation, is reported. Long-term steroid treatment for chronic obstructive pulmonary disease may have been a risk factor. A 12-day course of intravenous amphotericin B at a cumulative dose of 750 mg, followed by oral fluconazole at a daily dose of 600 mg for six weeks, resulted in healing of the skin lesion. Manifestations of primary cutaneous cryptococcosis in immunocompetent or immunocompromised patients are reviewed.

Topics: Administration, Oral; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fingers; Fluconazole; Humans; Immunocompromised Host; Lung Diseases, Obstructive; Male; Steroids

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Child; Cryptococcosis; Drug Carriers; Drug Therapy, Combination; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Liposomes; Recombinant Proteins

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fatal Outcome; Humans; Liver Cirrhosis; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Subdural Effusion; Tomography, X-Ray Computed

Topics: Amphotericin B; Anorexia; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Fluconazole; Flucytosine; Gynecomastia; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney Diseases; Liposomes; Male; Mixed Function Oxygenases; Mucormycosis; Nausea; Paracoccidioidomycosis; Sporotrichosis; Teratogens

Disseminated cryptococcosis is a major cause of morbidity and mortality in immunocompromised individuals, especially those with the acquired immunodeficiency syndrome (AIDS). Early diagnosis and treatment greatly improves the outcome, so clinical clues that lead to prompt diagnosis are important.. Three patients with AIDS in whom multifocal choroiditis and choroidal lesions were the initial signs of disseminated cryptococcosis were treated with systemic amphotericin B and flucytosine. All of the patients had a systemic work-up that included evaluation of the cerebral spinal fluid (CSF).. All three patients who were seen with the choroidal lesions as the presenting sign were noted to have either positive titers for cryptococcus or cultures that grew cryptococcus in the CSF. The choroidal lesions are presumed to be due to cryptococcus as no histopathologic or microscopic studies were available for ocular tissues. The choroidal lesions started to resolve one to three months after systemic treatment with amphotericin B and flucytosine.. Primary choroidal lesions in patients with AIDS may herald severe systemic disseminated disease. Funduscopic examination, however, may detect disseminated cryptococcal disease before other overt clinical manifestations, thereby allowing prompt institution of effective therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Flucytosine; Fluorescein Angiography; Humans; Male

Continuous spinal anesthesia technique with portex sets was used for treatment of neuroinfection. The patients was 43 years old woman with meningitis caused by Cryptococcus sp. suffered from chronic kidney failure, after transplantation and graft removal because of it's rejection. Effectiveness of therapy confirmed high value of CSA not only for pain treatment, but for central nervous system diseases as well.

Topics: Adult; Amphotericin B; Anesthesia, Spinal; Anti-Bacterial Agents; Cryptococcosis; Female; Graft Rejection; Humans; Injections, Spinal; Kidney Failure, Chronic; Kidney Transplantation; Meningitis; Pain

We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC). PC was the first AIDS-defining manifestation in nine patients. HIV infection was identified simultaneously with the onset of PC in 4 patients. The CD4+ lymphocyte count was low in all cases (median, 24/m3). Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases. In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient. For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans. Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture. Serum cryptococcal antigen was detected in all 15 patients. Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients. First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients. Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; HIV Infections; Humans; Lung Diseases, Fungal; Male; Middle Aged; Pneumonia, Pneumocystis; Radiography, Thoracic; Retrospective Studies

During 1995, among 1105 HIV patients explored in our department, 64 presented a deep fungic infection (5.8%). The yeast was searched for in cerebrospinal fluid, blood, urine, and bronchoalveolar aspiration. Isolated germs were Cryptococcus neoformans (95%), Candida tropicalis (1 case), Saccharomyces cerevisiae (1 case) et Aspergillus fumigatus (1 case). Results of treatment with amphotericin B were: recovery (9%), clinical success (11%), out of sight (14%), letality (66%), relapse (23%) and side effects (19%). We emphasized diagnostical and therapeutical difficulties, and bad prognostic of mycoses in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Body Fluids; Candida; Candidiasis; Cote d'Ivoire; Cryptococcosis; Cryptococcus neoformans; Humans; Mycoses; Prognosis; Saccharomyces cerevisiae

Six cases (3 cats, 3 dogs) of cryptococcosis were cured using combination chemotherapy that included amphotericin B. We developed a simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion during the treatment of these patients. For this, the calculated dose of amphotericin B (0.5 to 0.8 mg/kg) was added to 400 mL, for cats, or to 500 mL, for dogs, of 0.45% saline containing 2.5% dextrose. These amounts were given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg body weight. Subcutaneous infusions were generally well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L resulted in local irritation. This protocol enabled the administration of larger, and thus more effective, quantities of amphotericin B without producing marked azotaemia.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Cat Diseases; Cats; Cryptococcosis; Dog Diseases; Dogs; Drug Administration Schedule; Drug Therapy, Combination; Flucytosine; Injections, Subcutaneous; Male; Triazoles

We retrospectively analyzed clinical outcome of meningeal and extrameningeal cryptococcosis in HIV-negative patients treated with amphotericin B (43 patients) or fluconazole (40 patients). Amphotericin B and fluconazole were prescribed equally to patients with neoplastic diseases and no risk factor, but organ transplant recipients and patients with other diseases were mostly given fluconazole and amphotericin B, respectively. Patients with more severe infections (i.e., meningitis, neurological disorders, or higher levels of antigen in cerebrospinal fluid) were more frequently treated with amphotericin B. A cure rate of > 70% was achieved regardless of the initial treatment and the severity of the infection. A Cox regression analysis showed that age of > 60 years, neoplastic disease, abnormal mental status, disseminated infection at the time of diagnosis, and therapeutic failure were independent predictors of death. Although fluconazole appears to be as effective as amphotericin B, only a prospective multicenter study will determine the best treatment regimen for patients with cryptococcal meningitis who do not have AIDS.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Fluconazole; France; HIV Seronegativity; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Retrospective Studies; Treatment Outcome

In a murine model of intracerebral infection by Cryptococcus neoformans the therapeutic effects of pentoxifylline or dexamethasone were studied alone and in combination with amphotericin B. Assessed parameters were mean survival time, brain histopathology index, amounts of glutamate and gamma-aminobutyric acid in the brain, and yeast CFU per brain. Survival increased significantly in mice treated with dexamethasone, amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline; the latter had significantly longer survival than other treated groups. Indices of histopathological damage were similar in all treated groups. In infected untreated mice, the amounts of glutamate in the brain were decreased, presumably by depletion. In mice treated with amphotericin B plus dexamethasone, glutamate levels returned to the range of control mice. No differences in the amounts of gamma-aminobutyric acid were found between control and treatment groups. Brain fungal counts were significantly lower in mice treated with amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline than in untreated animals. In this model, pentoxifylline in combination with amphotericin B improved survival, decreasing the fungal burden, and has potential as adjuvant therapy in cerebral cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Brain Chemistry; Brain Diseases; Cryptococcosis; Dexamethasone; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Glutamic Acid; Mice; Pentoxifylline; Survival Analysis

We report the case of a 43 year old male patient, with normal immune function, who presented with right middle and lower lobe collapse. At bronchoscopy, a white lobulated lesion was seen, completely obstructing the origin of bronchus intermedius. Bronchial washings and biopsy of the lesion demonstrated cryptococcal organisms. The patient responded clinically and radiologically to amphotericin B and flucytosine; however, repeat bronchoscopy revealed only partial resolution of the endobronchial lesion.

Topics: Adult; Amphotericin B; Antifungal Agents; Bronchial Diseases; Bronchoscopy; Cryptococcosis; Flucytosine; Humans; Lung Diseases, Obstructive; Male; Radiography

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Humans; Male; Peritonitis

We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections. Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage. Both patients had had severe abdominal involvement during the acute PCM disease. Immunological evaluation showed cellular and humoral immunity impairment. Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other. The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine. Both patients had a good response to treatment with complete regression of the lesions. They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection. PCM also did not reactivate. The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C. neoformans infections of AIDS and transplant patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections; Paracoccidioidomycosis

Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Drug Therapy, Combination; Encephalitis; Fatal Outcome; Female; Fluconazole; Flucytosine; HIV Seronegativity; Humans; Immunologic Deficiency Syndromes

A case of acquired immunodeficiency syndrome (AIDS) developed cryptococcosis which was successfully treated with amphotericin B (AMPH) and fluconazole (FLCZ) is reported. A 52-year-old man was admitted because of pyrexia and oral candidiasis. He had a history of multiple sexual exposures to persons at risk for AIDS in Thailand. On admission, serologic tests for human immunodeficiency virus (HIV)-1 were positive on both EIA and Western blot analysis for anti-HIV-1 antibody. Furthermore, test for cryptococcal antigen and fungal cultures from blood and cerebrospinal fluid revealed that he was suffering from cryptococcemia and cryptococcal meningitis. In spite of identification of Cryptococcus neoformans in his blood and cerebrospinal fluid, the finding of cerebrospinal fluid had a minimal inflammatory response with mild elevation of protein. He was initially treated with intravenous AMPH, 10 to 30 mg a day, for 7 weeks, and then was given oral FLCZ, 400 mg a day, for the suppressive therapy. His fever subsided three weeks after the start of AMPH therapy. He was eventually discharged 9 weeks after the start of therapy without any symptoms, and continued to receive oral FLCZ as an out-patient. Thus, attention should be paid to diagnosis and treatment for cryptococcal meningitis in AIDS patients.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; HIV-1; Humans; Male; Meningitis, Cryptococcal; Middle Aged

Amphotericin B, alone or combined with flucytosine, is the reference curative treatment for neuromeningeal cryptococcosis associated with the acquired immune deficiency syndrome (AIDS). Treatment of non-meningeal forms is less well standardized. Out of 75 human immunodeficiency virus (HIV)-infected patients with cryptococcosis, 16 had no meningeal involvement. One died before receiving any treatment, another received amphotericine B and recovered, and the remaining 14 received curative therapy with fluconazole (200-400 mg/day); 11 of the latter entered complete remission, while three deteriorated during the first week of treatment but recovered on amphotericin B combined, in two cases, with fluconazole. Only one relapse occurred during maintenance treatment with low-dose fluconazole (100 mg/day). No adverse effects of fluconazole treatment were observed. One of the patients on amphotericin B developed acute renal impairment requiring drug withdrawal. These results suggest that first-line fluconazole therapy is effective and well tolerated in patients with AIDS-associated non meningeal cryptococcosis.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Fluconazole; Follow-Up Studies; Humans; Male; Middle Aged

Cryptococcosis is a common opportunistic infection in adults with AIDS. Few cases of cryptococcosis complicating pediatric AIDS have been reported. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of cryptococcosis in a large population of HIV-infected children.. We identified the cases of cryptococcosis through a retrospective review of the hospital records of the 473 HIV-infected children prospectively monitored in the Pediatric Branch of the National Cancer Institute during the 8 years from 1987 to 1995.. Four (0.85%) patients developed cryptococcosis during the study period. All patients had profound depression of the absolute CD4 counts, a history of previous opportunistic infections, and onset of cryptococcosis in the second decade of life. Cryptococcosis developed as a disseminated infection or a localized process of the lungs. Intermittent fever was the most common presenting manifestation. Serum cryptococcal antigen was positive in all patients and gradually declined after the institution of the antifungal therapy. All patients were treated with amphotericin B with or without flucytosine as initial therapy. Suppressive therapy consisted of fluconazole with or without flucytosine. There were no deaths due to Cryptococcus neoformans.. Cryptococcosis is an infrequent yet treatable opportunistic infection of advanced pediatric AIDS that may present with subtle manifestations and warrants careful consideration in the evaluation of febrile HIV-infected children.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Child; Cryptococcosis; Female; Humans; Male; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Animals; Antifungal Agents; Antigens, Fungal; CD4 Lymphocyte Count; Cryptococcosis; Diagnosis, Differential; Disease Progression; Drug Resistance, Microbial; False Positive Reactions; Fluconazole; Humans; Latex Fixation Tests; Mice; Polysaccharides

7 of 8 dogs receiving combination drug therapy consisting of flucytosine together with amphotericin B and/or a triazole for cryptococcosis or aspergillosis developed cutaneous or mucocutaneous eruptions during the course of treatment. Lesions resolved in all cases following discontinuation of flucytosine despite continued administration of other antifungals, suggesting the eruption was referable primarily to the flucytosine component of therapy. Lesions developed 13 to 41 days (median 20 days) after commencing flucytosine (105 to 188 mg/kg/day divided and given every 8 h; median dose rate 150 mg/kg/day). The cumulative dose of flucytosine given prior to the first signs of the drug eruption ranged from 1.7 to 6.8 g/kg (median 2.3 g/kg). The eruptions consisted of depigmentation, followed by ulceration, exudation and crust formation. The scrotum was affected in all 4 male dogs, the nasal plane in 6 of 7 cases, while the lips, vulva, external ear canal and integument were involved in a smaller number of cases. There was considerable variation in the severity of lesions, with changes being most marked when flucytosine was continued for several days after lesions first appeared. Some dogs experienced malaise and inappetence in association with the suspected drug eruption. Healing took a variable period, typically in excess of 2 weeks after discontinuing flucytosine, with up to 2 months being required for total resolution of the lesions. All lesions resolved eventually without scarring or permanent loss of pigment.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Cryptococcosis; Dog Diseases; Dogs; Drug Eruptions; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Itraconazole; Male

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Humans; Male

Cryptococcosis, caused by Cryptococcus neoformans, is the most common life-threatening AIDS-related fungal infection. The infection can occur in any organ of the body, although meningitis is its most frequent form. Symptoms of cryptococcal meningitis appear gradually and generally include headache, fever, or malaise. Symptoms may also include memory loss, lethargy, and personality changes. Isolation of the pathogen is done by using microscopy of the cerebrospinal fluid or by testing the serum antigen titer. Appropriate therapy includes amphotericin B or triazole antifungals. Patients with elevated intracranial pressure may be treated by draining cerebrospinal fluid (about 30 ml) daily. Other antifungal agents are being investigated.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Meningitis, Cryptococcal

A 59-year-old Caucasian male patient with AIDS is described who presented with an oral lesion of cryptococcosis. The gingival ulceration was the only detectable lesion of cryptococcosis. Diagnosis was established by histopathologic findings from biopsy and detection of serum cryptococcal antigen. The patient was treated with amphotericin B and flucytosine. After four weeks of therapy cryptococcal antigen turned negative. The oral ulceration diminished in size, but an inflammatory tissue reaction persisted.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Dental Care for Chronically Ill; Drug Therapy, Combination; Fatal Outcome; Flucytosine; Gingival Diseases; Humans; Male; Middle Aged; Mouth Diseases; Ulcer

A 30-year-old patient with the acquired immunodeficiency syndrome (AIDS) had limbal nodules and multifocal choroidal lesions.. A biopsy of the limbal nodules was performed.. The biopsy showed Cryptococcus neoformans surrounded by thick mucinous capsules without inflammatory cell infiltration.. In the differential diagnosis of limbal mass in patients with AIDS, cryptococcal infection should be considered.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Choroid Diseases; Choroiditis; Corneal Diseases; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Eye Infections, Fungal; Humans; Limbus Corneae; Male; Retinal Hemorrhage

We report a case of primary pulmonary cryptococcosis. A 20-year-old woman was admitted to the hospital complaining of coughing, fever, and dyspnea on exertion. She had no underling disease or immunological abnormality. Chest X-ray film revealed bilateral diffuse infiltrative shadows, which were first believed to have been caused by a community-acquired pneumonia. Pulmonary cryptococcosis was diagnosed from the results of a transbronchial lung biopsy. After 2.5 years of anti-mycotic chemotherapy with amphotericin B and flucytosine, pneumothorax occurred in the left lung. Thoracotomy and open lung biopsy were done. Histological findings of the open lung biopsy specimens showed numerous broken cryptococcal organisms within alveolar macrophages. Diffuse fibrosis accompanied by multiple bullae may have punctured bullae or blebs and thus led to pneumothorax.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Lung Diseases, Fungal; Pneumothorax

Topics: Adult; Amphotericin B; Cryptococcosis; Fatal Outcome; Fluconazole; HIV Seropositivity; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Tomography, X-Ray Computed

Topics: Adult; Amphotericin B; Cryptococcosis; Fluconazole; Flucytosine; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Resistance; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Meningitis, Cryptococcal

A 7-year-old child had unusual manifestation of cryptococcosis; liver and lymph node involvement predominated. There was evidence of cryptococcal hepatitis, extrahepatic biliary obstruction, and subsequent cirrhosis of the liver. Despite widespread dissemination, underlying immune disturbance was not evident. The patient was treated with two courses of amphotericin and 5-flucytosine.

Topics: Amphotericin B; Child; Cholestasis, Extrahepatic; Cryptococcosis; Flucytosine; Hepatitis; Humans; Liver; Liver Cirrhosis; Lymphatic Diseases; Male

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anaphylaxis; Antifungal Agents; Cryptococcosis; Drug Carriers; Humans; Liposomes; Male

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Administration Schedule; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Intravenous; Male

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Humans; Meningitis, Cryptococcal

We report a young homosexual male with AIDS that presented a systemic Cryptococcus neoformans infection. He had skin, lymph node and colonic involvement but the central nervous system was spared. Treatment was started with amphotericin B, achieving a good remission of skin lesions. However, malaise and digestive symptoms did not abate and the patient died.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Humans; Itraconazole; Lymph Nodes; Male; Meningitis, Cryptococcal; Prognosis; Skin

Topics: Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Eosinophils; Fever; Humans; Hypereosinophilic Syndrome; Infant; Leukocyte Count; Lymph Nodes; Male

We describe here a case of cryptococcal empyema thoracis and periauricular pyogenic abscess in a child with Bruton's agammaglobulinaemia. The cryptococcal empyema thoracis was treated with intravenous amphotericin B and intravenous fluconazole for six weeks followed by oral fluconazole. The pyogenic periauricular abscess was surgically drained and treated with intravenous ceftazidime and cloxacillin for two weeks. He also received monthly intravenous immunoglobulin.

Topics: Abscess; Agammaglobulinemia; Amphotericin B; Ceftazidime; Child, Preschool; Cloxacillin; Combined Modality Therapy; Cryptococcosis; Empyema, Pleural; Fluconazole; Humans; Immunization, Passive; Male; Opportunistic Infections; Otitis Externa

BRL 49594A (BRL) is a water soluble analogue of amphotericin B which has been developed as a polyene with efficacy similar to amphotericin B but with much reduced toxicity. BRL was prepared in 5% glucose, and was used to treat mice experimentally infected with Aspergillus fumigatus, Cryptococcus neoformans, or Histoplasma capsulatum. In the models in which BRL and amphotericin B were compared, BRL was well tolerated but was less effective than a similar regimen of amphotericin B. However, the ability to give much larger doses of BRL than tolerated with amphotericin B suggest that this drug could be an alternative to amphotericin B.

Topics: Amphotericin B; Animals; Anti-Infective Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cryptococcosis; Cryptococcus neoformans; Histoplasmosis; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses; Rats; Rats, Sprague-Dawley

Cells of five strains of Cryptococcus neoformans were obtained for partial analysis of lipid composition. Quantitative analysis of lipids and sterols were completed, as well as qualitative analysis of sterols by thin-layer chromatography and by the ultraviolet spectra. Such determinations were made on cells cultured in the absence and presence of amphotericin B at sub-MIC (minimal inhibitory concentration) levels. Marked alterations of the lipid and sterol contents were observed in the amphotericin B-treated cells. Moreover, ergosterol disappeared in these antibiotic-exposed cells. It is concluded that amphotericin B altered the lipid profiles, especially sterols of C. neoformans.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Ergosterol; Humans; Kidney Transplantation; Membrane Lipids; Microbial Sensitivity Tests; Postoperative Complications; Sterols

A case of primary pulmonary cryptococcosis is reported. A 76-year-old man, without underlying disease or immunological abnormalities, was admitted to the hospital. Chest X-ray revealed diffuse infiltrative shadows considered at first to be community-acquired pneumonia. A diagnosis of pulmonary cryptococcosis was performed using fluconazole, miconazole and transbronchial inhalation of amphotericin B. Cryptococcal antigen detection was performed by two latex agglutination methods: Crypto-test and Sero-direct test (Eiken-test). Comparing the results of the two tests, sensitivity was superior with the Sero-direct test, but the correlation between the titers of the two tests was good.

Topics: Aged; Amphotericin B; Cryptococcosis; Fluconazole; Humans; Lung Diseases, Fungal; Male; Miconazole; Tomography, X-Ray Computed

Topics: Adrenal Cortex Hormones; Amphotericin B; Controlled Clinical Trials as Topic; Cryptococcosis; Fluconazole; HIV Infections; Humans; Isoniazid; Pneumonia, Pneumocystis; Prospective Studies; Tuberculosis

The effect of recombinant interferon-gamma (rIFN-gamma) on Cryptococcus neoformans infection was investigated in vivo. BALB/c mice were injected intravenously with 2 x 10(6) C. neoformans. rIFN-gamma alone (10 micrograms intraperitoneally 18 h before, at, 24 h after infection) significantly increased the survival and decreased the colony-forming unit counts in the lungs compared with untreated mice. rIFN-gamma association significantly enhanced the effect of a single dose of amphotericin B (0.25 mg/kg 24 h after infection) to prolong mouse survival and to reduce colony counts in the brain. Tumor necrosis factor-alpha levels, measured in spleen 3, 6, and 24 h after infection, were not increased by rIFN-gamma. These results suggest that exogenous rIFN-gamma might improve the effect of antifungal therapy during cryptococcosis.

Topics: Amphotericin B; Animals; Cryptococcosis; Drug Therapy, Combination; Interferon-gamma; Male; Mice; Mice, Inbred BALB C; Recombinant Proteins; Tumor Necrosis Factor-alpha

A 67-year-old previously healthy woman presented with low back pain of 2 months duration and daily fever of 39 degrees C for 3 weeks. CT scan showed a lytic lesion in the third lumbar vertebra and a small right lower lobe lung infiltrate with mediastinal lymphadenopathy. Culture of material obtained from open biopsy of the vertebra grew Cryptococcus neoformans var. neoformans, which was also demonstrated on histology. Cryptococcal antigen was detected in the patient's serum. Treatment with amphotericin B (1000 mg total dose) and oral 5-fluorocytosine, resulted in complete recovery and resolution of the chest X-ray findings with a follow-up of 2 years. Since this case, as well as most of the previously described cases of cryptococcal osteomyelitis, were in normal hosts, cryptococcal osteomyelitis should be considered in the differential diagnosis even in a normal host, and therefore, prior to possible invasive diagnostic procedures, cryptococcal antigen in the serum should be determined.

Topics: Aged; Amphotericin B; Antigens, Fungal; Biopsy; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Flucytosine; Humans; Osteomyelitis; Spinal Diseases

Cutaneous cryptococcosis usually is associated with concurrent systemic infection and actually may develop before clinical manifestations of cryptococcal meningitis become apparent. It is rare for a cryptococcal infection to be localized only to the skin. A case of cutaneous cryptococcosis is described in an immunocompromised patient who initially had a rash and a positive serum cryptococcal antigen titer, but no central nervous system involvement. The papular pustular skin lesions disappeared after 8 weeks of therapy with amphotericin B, which was stopped secondary to progressive azotemia. Less than 2 months after therapy, the skin lesions recurred, again without evidence of systemic disease. Treatment with oral fluconazole resulted in a gradual resolution of the cutaneous lesions. The pathogenesis of cryptococcosis is discussed, with emphasis on the management of cutaneous cryptococcosis.

Topics: Aged; Aged, 80 and over; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Female; Fluconazole; Humans; Immunocompromised Host

Topics: Agammaglobulinemia; Amphotericin B; Child, Preschool; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Genetic Linkage; Humans; Immunoglobulin M; Male; X Chromosome

We compared the experimental toxicities and activities of deoxycholate amphotericin B (d-AmB) dissolved in glucose (Dd-AmB) or mixed with 20% Intralipid (ILd-AmB). In vitro, ILd-AmB against renal tubular cells in primary culture. In vivo, the toxicities and activities of Dd-AmB and ILd-AmB were studied in DBA2 mice with cryptococcosis. The maximum tolerated dose of intravenously administered d-AmB, i.e., the dose that induced less than 15% mortality because of toxicity, was 1.7 to 2.5 times higher when it was administered as ILd-AmB than when it was administered as Dd-AmB. Both treatments given intravenously at the same dose were equivalent for improving the survival of mice and reducing CFU counts in infected tissue, but at maximum tolerated doses, ILd-AmB (2 mg/kg of body weight) was more effective than Dd-AmB (0.8 to 1.2 mg/kg). AmB concentrations in spleen, liver, lung, and kidney were measured by high-pressure liquid chromatography 4 and 24 h after a single injection of 1.2 mg of Dd-AmB per kg, 1.2 mg of ILd-AmB per kg, or 2 mg of ILd-AmB per kg. In a given organ, AmB levels were similar after administration of 1.2 mg of Dd-AmB or ILd-AmB per kg but were significantly higher after administration of 2 mg of ILd-AmB per kg. The lower level of toxicity of ILd-AmB might be explained by circular dichroism experiments, showing that ILd-AmB contained 10-fold less soluble oligomeric AmB, which is believed to be the toxic form of the drug, than Dd-AmB. We conclude that ILd-AmB is as efficient as Dd-AmB and is better tolerated than Dd-AmB in mice with experimental cryptococcosis. By allowing higher doses of AmB to be infused, Intralipid enhances AmB concentrations in infected sites, and thus the therapeutic activity of the drug.

Topics: Amphotericin B; Animals; Cells, Cultured; Colony Count, Microbial; Cryptococcosis; Dose-Response Relationship, Drug; Drug Carriers; Fat Emulsions, Intravenous; Kidney Diseases; Kidney Tubules; Male; Mice; Mice, Inbred DBA; Rabbits

Amphotericin B (AmB) with deoxycholate (Fungizone) and AmB incorporated into mixed micelles (AmB-mixMs) composed of egg lecithin with glycocholate, deoxycholate, or taurocholate were compared as treatments for murine infections. For mice infected with Candida albicans, treatment consisted of a single intravenous injection; for mice infected with Cryptococcus neoformans, treatment consisted of two intravenous injections. The maximal tolerated doses of AmB as Fungizone were 1.25 mg/kg of body weight in mice with candidiasis and 2.5 mg/kg of body weight in mice with cryptococcosis. The AmB-mixMs were nontoxic to mice at doses of 80 and 100 mg/kg of body weight and were therapeutically more active than the maximal tolerated dose of Fungizone in both models of infection. However, when Fungizone or AmB-mixMs were administered at equivalent doses of AmB, AmB-mixMs were more active in treating murine candidiasis, whereas Fungizone was more active in treating murine cryptococcosis.

Topics: Amphotericin B; Animals; Bile Acids and Salts; Candidiasis; Cryptococcosis; Dose-Response Relationship, Drug; Drug Carriers; Drug Evaluation, Preclinical; Female; Mice; Mice, Inbred Strains; Micelles; Phosphatidylcholines

The therapeutic efficacy of the immunoglobulin G1 (IgG1) monoclonal antibody (MAb) 2H1 to the Cryptococcus neoformans capsular polysaccharide was studied with and without amphotericin B (AmB) in a murine model of intravenous (i.v.) infection. MAb and AmB were administered by intraperitoneal (i.p.) injection after i.v. infection with a C. neoformans serotype D strain. Intraperitoneal administration of MAb 2H1 resulted in rapid distribution to the intravascular compartment, and the half-lives of i.p. and i.v. administered MAb were similar. Administration of MAb 2H1 alone resulted in increased survival, decreased lung fungal burden, and reduced serum glucuronoxylomannan antigen levels when given 2 to 6 h but not 24 h after infection. In vivo, the combination of MAb 2H1 and AmB was more effective at prolonging survival than either agent alone. MAbs of IgM, IgG1, IgG3, and IgA isotypes given 1 day after infection were effective in reducing serum GXM-D levels, with their relative efficacy being IgG1 > IgG3 > IgM > IgA. In vitro, MAb 2H1 was a potent opsonin of C. neoformans and the combination of MAb 2H1 and AmB was more effective than either agent alone in decreasing C. neoformans colony counts in the presence of the murine macrophage cell line J774.16. The results confirm that capsule-binding MAbs can enhance the effect of AmB against C. neoformans and provide support for considering combined therapy in humans.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Cell Line; Combined Modality Therapy; Cryptococcosis; Cryptococcus neoformans; Female; Injections, Intraperitoneal; Lung; Macrophages; Mice; Mice, Inbred A; Phagocytosis; Polysaccharides

Topics: Adolescent; Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Fluorouracil; Humans; Lung Diseases, Fungal; Male; Middle Aged; Serologic Tests

Photopheresis is being used with increasing frequency as therapy for patients with neoplastic and dermatologic diseases and is being evaluated as therapy for patients with AIDS. We describe a patient with advanced cutaneous T cell lymphoma who developed pulmonary and cutaneous cryptococcosis after receiving therapy with photopheresis and biweekly methotrexate. We consider the potential roles of cutaneous T cell lymphoma, methotrexate, and photopheresis as predisposing factors in the development of serious cryptococcal infections.

Topics: Aged; Amphotericin B; Chemotherapy, Adjuvant; Cryptococcosis; Dermatomycoses; Humans; Immunocompromised Host; Lymphoma, T-Cell, Cutaneous; Male; Methotrexate; Photopheresis

A 33 year old man with AIDS presented with fever, dyspnoea, cough and a miliary pattern on the chest radiograph. Cryptococcus neoformans infection was diagnosed from bronchoalveolar lavage bronchoscopy. This case supports the principle that, in patients with AIDS, pulmonary infections can exhibit variable radiographic features and that definitive diagnosis should always be considered.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Humans; Lung Diseases, Fungal; Male

We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Fluconazole; Humans; Incidence; Lung Diseases, Fungal; Male; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination

Itraconazole is a lipophilic triazole with potent in vitro activity. It is also effective after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth). Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp. (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C. albicans, Cr. neoformans, Histoplasma duboisii, S. schenckii, P. marneffei and A. fumigatus. It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies have yet been undertaken for other deep mycoses. The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Guinea Pigs; Immunocompromised Host; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Mycoses; Sporotrichosis

A comparative study, using 5 antifungal drugs for the treatment of an experimental model of murine cryptococcosis, was carried out. One hundred and eighty Balb C mice, divided in 18 groups of 10 animals each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans var. neoformans. Twelve groups were treated with different schedules beginning 5 days after inoculation, for 2 or 4 weeks. The treatments were the following: amphotericin B (6 mg/kg/every other day, intraperitoneally); 5-fluorocytosine (300 mg/kg/day, by gavage); amphotericin B (6 mg/kg/every other day, intraperitoneally) in association with 5-fluorocytosine (300 mg/kg/day, by gavage); fluconazole, itraconazole and Sch 39.304 (all at the daily dose of 16 mg/kg, by gavage). The six remaining groups were used as controls and received the solvent for the drugs. The evaluation of the efficacy of the different treatments was based on: survival time; macroscopy of brain, lungs, liver and spleen at autopsies; presence of encapsulated yeasts in microscopic examination of wet preparations of these organs; and cultures of a concentrated suspension of brain and lungs. In the animals treated for 2 weeks, the combination of amphotericin B + 5-fluorocytosine was the most useful; it negativized the micro and macroscopic findings as well as 90% of the cultures, and prolonged the survival time up to 60 days. Sixty per cent of the mice which received amphotericin B exhibited the same survival time and macroscopic findings as those treated with the association of amphotericin B + 5-fluorocytosine. Among the azolic compounds, Sch 39.304 proved to be the most effective in the prolongation of survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; Itraconazole; Ketoconazole; Mice; Mice, Inbred BALB C; Triazoles

The first documented case of algal meningitis due to Prototheca wickerhamii is reported in a patient with AIDS. The initial CSF culture yielded only Cryptococcus neoformans. P. wickerhamii was isolated on four subsequent lumbar punctures. The patient died, and at autopsy the alga was isolated from leptomeninges over the brain and about the spinal cord. Histologic sections from numerous locations of the brain revealed masses of cryptococci and prototheca.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Humans; Meningitis; Meningitis, Fungal; Prototheca

We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age. His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age. He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies. Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters. Immunoglobulin levels and specific antibodies were normal. The patient has been in good health since treatment of his osteomyelitis. However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid. Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes. The generation of messenger ribonucleic acid for interleukin-4 was not affected. Interferon-gamma was produced at subnormal levels. The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors. The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency. Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; HLA Antigens; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Activation; Lymphocyte Subsets; Male; Osteomyelitis; Scapula

The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated cryptococcosis. Mice were treated intravenously with either ABDS at 0.2, 0.8, or 3.2 mg/kg of body weight per dose or ABCD at 0.8, 3.2, 6.4, 12.8, or 19.2 mg/kg dose three times per week for 2 weeks. Excluding mice treated with ABDS at 3.2 mg/kg, which was acutely lethal in 100% of mice, and ABCD at 19.2 mg/kg, which also resulted in two early deaths, the survival of ABCD- and ABDS-treated groups was prolonged over survival of controls (P < or = 0.05). Survival of ABCD (3.2 mg/kg)-treated mice was improved over that of ABDS (0.2 mg/kg)-treated mice (P < 0.05); however, comparisons of mice given all other dosages of ABCD with mice given sublethal dosages of ABDS did not demonstrate differences in survival. Comparative fungal burdens in organs showed a decrease in liver (P < 0.05) and spleen (P < 0.05) burdens for ABCD with the 19.2-mg/kg therapy versus those with ABDS with the 0.8-mg/kg therapy and liver burdens for ABCD with the 12.8-mg/kg therapy versus ABDS with the 0.8-mg/kg therapy (P < 0.05). There was no difference in organ burdens between therapy with ABCD at 0.8 mg/kg and ABDS at 0.8 mg/kg. These data show that the efficacy of ABCD is equal to that of ABDS on a milligram-per-kilogram basis for murine disseminated cryptococcosis. Because of its decreased toxicity, greater efficacy with ABCD could be achieved through doses fourfold higher than the 100% lethal dose for ABDS. Thus, ABCD shows promise as an effective but less toxic alternative to ABDS for the treatment of disseminated cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Female; Mice; Suspensions

The in vitro and in vivo toxicities and activities of MS-8209, a new hydrosoluble amphotericin B (deoxycholate-amphotericin B [D-AmB]; Fungizone) derivative, were studied. In vitro, MS-8209 was less toxic than AmB against renal tubular cells in primary culture and less active against Candida albicans and Cryptococcus neoformans. However, at 10-fold the AmB concentration, MS-8209 in vitro antifungal activity paralleled that of AmB. Fifty-percent lethal doses of MS-8209 and D-AmB in OF1 noninfected mice were 26 and 2.3 mg/kg, respectively. Therapeutic efficacy of MS-8209 was assessed in murine candidiasis, cryptococcosis, and aspergillosis. In each model of infection, we determined the maximum tolerated dosages of MS-8209 and D-AmB, i.e., the dosage inducing less than 15% mortality due to toxicity; the efficacies of MS-8209 and D-AmB at their respective maximum tolerated dosages were compared. In candidiasis, MS-8209 (15 mg/kg) significantly increased the survival time compared with D-AmB (0.5 mg/kg). Both compounds were equally effective at reducing CFU counts in the kidney. MS-8209 was the most effective agent for increasing the survival time in cryptococcal meningoencephalitis and for reducing CFU counts in spleen, brain, and lung during both cryptococcal pneumonia and meningoencephalitis. In aspergillosis, MS-8209 and D-AmB similarly prolonged the survival of treated mice compared with controls. These results show that when MS-8209 and D-AmB were used at the maximum tolerated dosage, MS-8209 was as effective as or more effective than D-AmB for the treatment of systemic mycoses. These findings warrant further experiments to study the pharmacokinetic properties and toxicity of MS-8209 under conditions of chronic administration.

Topics: Amphotericin B; Animals; Aspergillosis; Cells, Cultured; Cryptococcosis; Kidney Diseases; Kidney Tubules, Proximal; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mycoses; Rabbits

Cryptococcus infections of the lung and central nervous system have become major problems in immuno-compromised patients, leading to the need for additional treatment protocols. We have utilized a Cryptococcus-mouse model that mimics human cryptococcal disease to evaluate the efficacy of amphotericin B-liposomes (AmpB-Lip) when delivered by small-particle aerosol (SPA). In the model, initial intranasal inoculation leads to a pulmonary infection that spreads after 2 to 3 weeks to distant organs, including the brain. Aerosols of AmpB-Lip that were generated by a Collison nebulizer had mass median aerodynamic diameters of 1.8 microns and contained 10.3 micrograms of AmpB per liter. When AmpB-Lip SPA was begun at 24 h postinoculation, a single 2-h treatment (0.3 mg of AmpB per kg of body weight) was effective in reducing pulmonary Cryptococcus infection. This regimen was more effective than intravenous administration of AmpB-Lip given for 3 continuous days. This single 2-h exposure to AmpB-Lip also was effective in reducing pulmonary Cryptococcus infection when treatment was delayed for 7 or 14 days. At day 21, when organisms had spread to the brain in all animals, the single 2-h aerosol treatment reduced the number of cryptococci in the brain as well as in the lungs. AmpB-Lip SPA administered once for 2 h on days 7, 14, and 21 also was effective in increasing the duration of survival of infected animals. These results demonstrate that aerosolized AmpB-Lip can be effective in treating both local, pulmonary Cryptococcus disease and systemic disease.

Topics: Aerosols; Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Liposomes; Lung Diseases; Mice

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Drug Carriers; Humans; Liposomes; Male; Middle Aged

A 62-year-old woman without evidence of immunocompromise was evaluated for uveitis and a subretinal lesion in the right eye. Laboratory evaluation, including cerebrospinal fluid analysis, revealed no apparent cause. The diagnosis of subretinal cryptococcosis was established by transscleral needle biopsy of the subretinal mass. Treatment with intravenous amphotericin B and oral 5-flucytosine brought recovery of visual acuity to 20/30-1 and resolution of the inflammation. This patient demonstrates that ocular cryptococcal infection must be suspected, even in the absence of predisposing factors or systemic findings, and that subretinal fine-needle aspiration is an important diagnostic tool in this setting.

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Eye Infections, Fungal; Female; Flucytosine; Fluorescein Angiography; Fundus Oculi; Humans; Immunocompromised Host; Middle Aged; Retinal Diseases; Visual Acuity

A 47-year-old man with cirrhosis developed a case of previously unreported olecranon bursitis due to Cryptococcus neoformans. Most patients with disseminated cryptococcosis have deficiencies in cell mediated immunity. Cirrhosis may be an independent risk factor because of impaired chemotaxis and phagocytosis.

Topics: Amphotericin B; Bursitis; Cryptococcosis; Elbow; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged

Cryptococcosis is more frequently observed since the appearance of the acquired immunodeficiency syndrome (AIDS). AIDS has modified the clinical and evolutive forms of the disease. This study reviews the changes produced in the infection from the context of AIDS.. The present is a retrospective study (1985-1990) including patients presenting: 1) a positive latex agglutination test (serum or spinal fluid) or 2) a Sabouraud culture positive for cryptococcus. Clinical histories were revised collecting clinical, radiologic, analytic, therapeutic and evolutive data.. Twenty-six patients (21 males) were included in the study. Twenty patients had the human immunodeficiency virus. The clinical picture was: 22 cases with cryptococcal meningitis (13 with hematogenous participation), 3 with pulmonary cryptococcosis and one with disseminated cryptococcosis without meningeal involvement. The patients with AIDS had: greater frequency of positive hemocultures, higher serologic titers and fewer with the meningeal syndrome. The number of T4 lymphocytes was lower than 150 elements/ml in AIDS patients. In 17 patients treatment with amphotericin B and 5-fluorocytosine was administered, 5 received amphotericin B and two fluconazole and two did not receive the above since they had not been diagnosed alive. There were 6 deaths and 10 relapses in 6 AIDS patients and none in the remaining patients.. The incidence of cryptococcosis has increased as a consequence of AIDS. In these patients the disease occurs in advanced stages of immunodeficiency and frequently in disseminated, severe and paucisymptomatic forms. Treatment is usually effective although a maintenance therapy is required to avoid relapse.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Aged, 80 and over; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus; Female; Flucytosine; Humans; Male; Middle Aged; Opportunistic Infections; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Fluconazole; Humans; Prognosis

Immunocompetent hosts usually do not require antifungal therapy for pulmonary cryptococcosis. We present a case of right lung mass and Pancoast's syndrome due to locally invasive Cryptococcus neoformans variety gattii in a normal host. Lobectomy followed by therapy with amphotericin B and flucytosine was curative.

Topics: Adult; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Horner Syndrome; Humans; Lung; Lung Diseases, Fungal; Male; Pancoast Syndrome; Serotyping; Tomography, X-Ray Computed

We discuss 19 cases of infection due to Cryptococcus neoformans diagnosed in 438 AIDS patients admitted to our center (4%). Fourteen of them showed meningitis confirmed by culture of C. neoformans in CSF. Clinical features were rather unspecific and disorders in CSF parameters were non striking. The diagnostic techniques performed with best results were culture of C. neoformans and antigen determination, especially in serum. Survival probability at one year was 75%. Treatment response was good. Treatment with fluocytosine did not seem to provide additional benefits versus amphotericin alone, neither in respect to clinical evolution nor regarding survival probability at one year. Fluconazole has shown effectiveness in maintenance therapy, being not be possible to evaluate it as an acute phase therapy because the low number of cases in which it was studied. It is advisable to follow a suppressive treatment, having found a 10% relapse rate in patients following therapy and a 50% in those who interrupted it.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; HIV-1; Homosexuality; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Substance Abuse, Intravenous

Churg-Strauss vasculitis (CSV) is an interesting but uncommon pulmonary vasculitis. Cavitation in CSV is distinctly unusual and should prompt a work-up for other causes. We have described a case of CSV complicated by pulmonary cryptococcosis, which was treated with a novel antifungal regimen.

Topics: Amphotericin B; Churg-Strauss Syndrome; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Lung; Lung Diseases, Fungal; Male; Middle Aged; Radiography

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Azoles; Costs and Cost Analysis; Cryptococcosis; Humans; Rwanda

This investigation examined the therapeutic efficacy of AmBisome, a unilamellar (55-75 nm) liposome amphotericin B preparation with a murine LD50 by the intravenous route of greater than 175 mg/kg amphotericin B. Both fungal burden and survival were used to evaluate the drug's efficacy against murine candidosis and cryptococcosis. Single and multiple dose intravenous treatment with AmBisome (2.5, 5.0 and 10.0 mg/kg) reduced the colony forming units/mg kidney in candida-infected mice by 99% and improved survival by at least 40% relative to untreated control mice. Repeated intravenous dosing of candida-infected mice with equivalent amounts (0.75 mg/kg) of conventional amphotericin B (Fungizone) or AmBisome showed comparable reduction of yeasts in the kidneys. When mice were infected systemically with Cryptococcus neoformans, all but one of the 30 mice given AmBisome (5.0, 7.5 or 10.0 mg/kg) survived until the experiment was terminated 35 days after infection. Liver and spleen cultures from AmBisome-treated mice were negative for fungal growth. All the mice given conventional amphotericin B intraperitoneally at 4.5 mg/kg survived and cleared the infection from the livers although some of the mice had infected spleens. The percentage of cultured brains free of cryptococcus was 89% following treatment with 10.0 mg/kg AmBisome, and 80% with 4.5 mg/kg conventional drug. These preclinical studies of systemic candidosis and cryptococcosis demonstrate comparable efficacy of AmBisome and conventional amphotericin B at low doses and improved efficacy with AmBisome at doses higher than can be safely administered of the conventional drug.

Topics: Amphotericin B; Animals; Candidiasis; Cryptococcosis; Drug Carriers; Female; Kidney; Liposomes; Mice; Mice, Inbred C57BL

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Confidence Intervals; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Prospective Studies; Prostatic Diseases; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Humans; Liposomes; Male

Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Male; Middle Aged; Opportunistic Infections

The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives. Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine. Administered intravenously, this therapy is associated with frequent and often severe side effects. Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects. The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis. Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments. Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members. U.K. health care costs were used to value these resources. The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment. Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Costs and Cost Analysis; Cryptococcosis; Delphi Technique; Drug Therapy, Combination; Fluconazole; Flucytosine; Hospitalization; Humans; Infusions, Intravenous; Meningitis; Models, Theoretical; Surveys and Questionnaires

A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination.

Topics: Adrenal Gland Diseases; Adrenal Gland Neoplasms; Amphotericin B; Combined Modality Therapy; Cryptococcosis; Diagnosis, Differential; Female; Humans; Middle Aged

Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported. We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS. After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Papilledema

Current therapy of cryptococcosis is unsatisfactory, particularly in patients with AIDS. Experimental cryptococcosis models in DBA/2 mice were used to determine whether the murine monoclonal anticryptococcal antibody (designated E1) might potentiate the chemotherapeutic effect of amphotericin B (AmB). According to the inoculum size, these mice died spontaneously from acute pneumonia (high inoculum) or from brain swelling (lower inoculum). AmB and E1 together significantly improved the survival of mice in both models compared with AmB alone. The mechanisms by which E1 might potentiate AmB activity were investigated in vitro. When cryptococci were preincubated with AmB or another polyene antibiotic, nystatin, there was an augmented binding of E1. AmB enhanced phagocytosis by unstimulated peritoneal macrophages in the presence of E1 or normal rabbit immunoglobulins. Normal and immune IgG deserve further study to determine under what circumstances the chemotherapeutic effect of AmB can be enhanced.

Topics: Amphotericin B; Animals; Antibodies, Fungal; Antibodies, Monoclonal; Cells, Cultured; Combined Modality Therapy; Cryptococcosis; Cryptococcus neoformans; Flow Cytometry; Immunization, Passive; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Phagocytosis

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Humans; Liposomes; Male; Meningitis

The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.

Topics: Amphotericin B; Animals; Aspergillosis; Candidiasis; Cryptococcosis; Dimyristoylphosphatidylcholine; Excipients; Female; Histoplasmosis; Liposomes; Mice; Mycoses; Phosphatidylglycerols

To assess the possible beneficial effects of combined therapy (fluconazole and flucytosine) in the treatment of cryptococcal meningitis in the immunocompromised host, we compared therapy with fluconazole and flucytosine, individually and combined, in the experimental murine model. BALB/c athymic (nu/nu) mice were infected intracerebrally with 150 to 300 CFU of Cryptococcus neoformans. In mortality studies, treatment was initiated 24 h postinfection and continued for 10 to 14 days with either fluconazole (1 to 15 mg/kg of body weight per day), flucytosine (60 to 120 mg/kg/8 h), both drugs, or 0.3% Noble agar (control). Combined therapy delayed mortality significantly when compared with controls and single-drug regimens. This was observed over a broad range of doses. Quantitative determinations of CFU in brain tissue demonstrated a significantly lower burden of C. neoformans in mice receiving combined therapy. The results indicate that combined therapy with fluconazole and flucytosine is superior to single-drug therapy.

Topics: Amphotericin B; Animals; Chromatography, Gas; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Meningitis; Mice; Mice, Inbred BALB C

This is a case report of fatal cryptococcal meningitis in a child with systemic lupus erythematosus being treated with prednisolone and azathioprine. It is believed to be the first case of cryptococcal meningitis recorded in a child in Saudi Arabia.

Topics: Amphotericin B; Azathioprine; Cerebrospinal Fluid; Child; Cryptococcosis; Diagnosis, Differential; Female; Flucytosine; Humans; Lupus Erythematosus, Systemic; Meningitis; Prednisolone

Experiments are described of the treatment of two patients with cryptococcal meningitis using antifungal drugs and amphotericin B. The first patient was a 56-year-old man with a slight azotaemia caused by hypertensive nephrosclerosis. Lumbar puncture revealed a positive India ink stain and a positive culture for Cryptococcus neoformans; serum titre for cryptococcal antigen was elevated. Amphotericin B was not administered because of the patient's slight azotaemia. After admission, the patient received oral and intravenous fluconazole (400 mg per day), for a total dose of 40 g of fluconazole over 103 days from October 1 while simultaneously receiving treatment with oral itraconazole (200 mg per day) from October 1 to December 5. In addition, he was given intravenous miconazole (600-1000 mg per day, total 74.4 g) and intrathecal miconazole (5-20 mg per day, total 375 mg) from December 1 to March 4 1990. Concomitantly, oral flucytosine (6 g per day) was given from December 5 to March 1 1990. Lumbar puncture performed at the completion of these treatments indicated the India ink stain still was positive and the serum titre for cryptococcal antigen high. Finally, amphotericin B alone was administered to the patient intravenously and intrathecally from March 4 to May 1, with an initial dose of 5 mg i.v. gradually increasing by 5 mg increments up to 50 mg per day. The patient's clinical symptoms immediately improved; the India ink stain became negative for the first time after admission and the serum titre for cryptococcal antigen also gradually decreased. On May 1, the patient was completely cured of cryptococcal meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Male; Meningitis; Miconazole; Middle Aged

Cryptococcosis is an opportunistic infection that is responsible for increased morbidity and mortality in patients with the acquired immunodeficiency syndrome. The high toxicity of the antifungal agent that is mainly used against cryptococcosis, amphotericin B (AMB), accounts for the need for new treatments, especially in patients with the acquired immunodeficiency syndrome because of the high relapse rate of cryptococcosis. Drug targeting may be one of these alternate treatments. Since we have demonstrated that an immunoglobulin G1 (IgG1) anti-Cryptococcus neoformans serotype A monoclonal antibody (E1) was protective during experimental cryptococcosis in mice, we investigated whether specific targeting of AMB with liposomes that bear E1 would improve the therapeutic index of the drug. For that purpose, in vitro and in vivo experiments were designed to compare the specificities and activities of these liposomes with those of control immunoliposomes bearing a nonrelated IgG1 monoclonal antibody (CY34). The immunoliposomes were prepared by covalently linking E1 or CY34 and small unilamellar vesicles. When immunoliposomes were incubated with yeast cells, only E1-bearing liposomes recognized C. neoformans. In vivo, mice that were treated 24 h after infection with one injection of AMB (0.12 mg/kg of body weight) intercalated into E1-bearing liposomes survived significantly longer than did those given the same dose of AMB alone or AMB intercalated into nontargeted liposomes or control immunoliposomes. None of the mice that were given control treatments did statistically better than those that were given AMB. Keeping in mind that this kind of therapy requires knowledge of the antigenic type of the infecting organism, the results suggest that specific targeting of small doses of AMB improve the efficacy of AMB and might be an alternative to the use of larger doses of AMB.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Cryptococcosis; Cryptococcus neoformans; Immunochemistry; Immunoglobulin G; Liposomes; Male; Mice; Mice, Inbred DBA; Microbial Sensitivity Tests

Topics: Administration, Oral; Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Fluconazole; Flucytosine; Humans; Infusions, Intravenous; Lung Diseases, Fungal; Miconazole; Mycoses

The triazole Bay R 3783 was compared with fluconazole, itraconazole, ketoconazole, and amphotericin B in rodent models of superficial and systemic candidiasis, meningocerebral cryptococcosis, and pulmonary aspergillosis. Overall, Bay R 3783 was comparable or slightly superior to fluconazole and markedly superior to itraconazole and ketoconazole in both survival and short-term organ load experiments in models of candidiasis and cryptococcosis but was less effective than amphotericin B. Of the antifungal agents tested, only Bay R 3783 and itraconazole showed any efficacy in the model of pulmonary aspergillosis.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Disease Models, Animal; Drug Administration Schedule; Evaluation Studies as Topic; Female; Fluconazole; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Male; Meningitis; Mice; Pharmaceutical Vehicles; Rats; Rats, Inbred Strains; Triazoles

Cryptococcosis is a systemic fungal disease and meningeal or meningoencephalitis involvement is the most serious complication. This is a retrospective analysis of 80 patients admitted from December 1983 to October 1985 (30 cases) and June 1987 to December 1988 (50 cases) in hospital of Bujumbura, Burundi, Central Africa. All patients have an AIDS. Clinically, the meningeal and meningoencephalitis attack prevails in 87% cases. The diagnosis in our study is essentially based on the examination of the CRL. Before the new antifungals, the treatment involved the association of amphotericin B and 5-fluorocytosine, during 6 to 8 weeks. This treatment was badly tolerated and the second falls, when the therapy was stopped, were frequent. Presently, the fluconazole is the best treatment of this affection (ailment?): it enables maintenance therapy for a disease in which the risks of recurrence and reinfection by the environment are not negligible in Africa.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Burundi; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Male; Middle Aged; Retrospective Studies

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Topics: Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Flucytosine; HIV Infections; Humans; Meningitis; Recurrence

Fungal infections have become one of the major causes of death among immunocompromised patients, particularly patients with AIDS. Accurate and quick diagnosis is difficult; therefore, empirical therapy is often necessary. This scenario is complicated by the fact that most antifungal agents are toxic at the doses used or relatively ineffective against deep-seated mycoses. Because the population of AIDS patients is increasing, physicians will be faced more often with the management of systemic fungal infections. Despite the current bleak prognosis for these patients, several new antigen detection tests are being developed and triazole agents are proving to be effective and less toxic than their predecessors. Many cases of systemic mycoses do result in mortality, but appropriate treatment can both prolong life and improve its quality.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Azoles; Candidiasis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Meningitis; Mycoses

Twenty-four consecutive patients with central nervous system cryptococcosis (C.C.) have been studied retrospectively. In contrary to many reports from America or Europe only two patients suffered from an underlying immunocompromising disease. All patients were treated uniformly by amphotericin B and 5-fluorocytosin. They were monitored closely and dose-adjustment was done according to laboratory data. None of the patients died. Sixteen were available for a six-month post-treatment follow-up: seven had various degrees of neurological long-term sequelae whereas nine had no complaints and neurological examination was without abnormal findings. Our series is compared with others both from tropical and non-tropical countries. In accordance with all but one larger series from the tropics the relatively good prognosis and extremely rare occurrence of C.C. in immunocompromised persons is noted. Since different varieties of Cryptococcus neoformans have been shown to exist in different climate zones, this might be one of the possible explanations for the lack of preceding immune-compromising conditions in persons suffering from C.C. in the tropics and the benign course of disease.

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Humans; Immune Tolerance; Male; Meningoencephalitis; Middle Aged; Prognosis; Retrospective Studies; Thailand

Topics: Adult; Amphotericin B; Cryptococcosis; Fluconazole; Flucytosine; Humans; Male; Meningitis

Topics: Amphotericin B; Azoles; Cryptococcosis; Humans

Two patients with acquired immune deficiency syndrome presented with headaches and fevers. A diagnosis of cryptococcal meningitis was made by lumbar puncture and elevated cryptococcal antigens. Complaints of decreased vision in both patients led to the diagnosis of optic disc edema and cryptococcal choroiditis with yellow-white choroidal infiltrates noted in both eyes of the two patients. Systemic treatment with amphotericin B and 5' flucytosine led to resolution of the choroidal infiltrates. Late visual acuity loss was believed to be secondary to optic atrophy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antigens, Fungal; Choroiditis; Cryptococcosis; Eye Infections, Fungal; Flucytosine; Fluorescein Angiography; Fundus Oculi; Humans; Male; Papilledema; Visual Acuity

Topics: Administration, Oral; Amphotericin B; Child; Cryptococcosis; Female; Fluconazole; Humans; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Recurrence

Disseminated histoplasmosis was diagnosed in 36 (4%) of 980 patients with AIDS seen at Parkland Memorial Hospital in Dallas, Texas before September 30, 1989. Diagnostic sensitivity of blood culture plus examination of peripheral smear was 88%; sensitivity of bone marrow aspiration and blood culture was 80%. Median CD4 lymphocyte count at diagnosis was 33/cu mm. Median actuarial survival from the date histoplasmosis was diagnosed was 188 days. Thirteen (36%) of the 36 patients died before adequate antifungal therapy could be administered, while 13 survived long enough to receive 1,500 mg of amphotericin B; actuarial survival of the latter group from the date 1,500 mg of amphotericin B had been infused was 47% at 1 year. The substantial early mortality of AIDS-associated disseminated histoplasmosis and the modestly encouraging survival of those who were diagnosed in time to receive adequate therapy raise the issues of surveillance, prophylaxis, and empiric therapy for this infection in selected HIV-positive patients.

Topics: Acquired Immunodeficiency Syndrome; Actuarial Analysis; Adult; Amphotericin B; Cryptococcosis; Evaluation Studies as Topic; Female; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Male; Middle Aged; Retrospective Studies; Texas; Time Factors

A case of SLE with moderately deteriorated renal function due to lupus nephritis developed cryptococcal meningitis. Long term administration of amphotericin B (cumulative dose 5 g) combined with 5-flucytosine eradicated this fungal infection. Throughout amphotericin B administration urinary excretions of Na and K, as well as plasma HCO3 concentration were monitored, and, Na, K and HCO3 were supplemented orally and intravenously so much as to replace their urinary losses. Neither prominent water-electrolyte disturbance nor severe azotemia, which are the most serious side effects of amphotericin B, did not ensue. This case study indicates that sufficient water.electrolytes supplementation is important to prevent the nephrotoxicity of amphotericin B.

Topics: Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Infusions, Intravenous; Lupus Erythematosus, Systemic; Meningitis; Prednisolone

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Disease; Heart Transplantation; Humans; Immunosuppression Therapy; Itraconazole; Ketoconazole; Male; Neoplasms; Opportunistic Infections

To assess the frequency of persistent Cryptococcus neoformans infection in patients with the acquired immunodeficiency syndrome (AIDS) after receiving apparently adequate treatment for meningitis.. Blood, urine, and cerebrospinal fluid were cultured at the conclusion of primary therapy to assess the adequacy of treatment.. Outpatient clinics at three medical centers.. Patients had C. neoformans grown in culture from cerebrospinal fluid. Primary therapy consisted of either 2.0 g of amphotericin B alone; 6 weeks of combination therapy with flucytosine; or, if flucytosine was poorly tolerated, an adjusted minimum total amphotericin B dose. To meet criteria for adequate treatment of meningitis all patients had two sequential cerebrospinal fluid samples which were culture negative.. Nine of forty-one patients grew C. neoformans from urine after completion of primary treatment, but none had urinary symptoms. Fungi were visualized in expressed prostatic secretions in 4 of these patients. One patient refused further treatment and developed cryptococcemia within 5 weeks. Three patients received additional amphotericin B; all had persistent funguria without systemic relapse. Six patients received fluconazole; 4 became urine culture negative, and 2 had systemic relapse.. The persistence of urinary C. neoformans after adequate therapy for meningitis suggests that the urinary tract (probably the prostate) is a sequestered reservoir of infection from which systemic relapse may occur.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Humans; Male; Meningitis; Prostatic Diseases; Recurrence; Triazoles; Urine

Cryptococcal meningitis is increasing in frequency, in large part because of the advent of acquired immune deficiency syndrome. Using the murine cryptococcosis model, a new oral triazole, SCH39304, has been compared with two drugs in clinical use, fluconazole and amphotericin B. BALB/c mice (nu/nu and nu/+) were challenged intracerebrally or intranasally. Oral treatment was given daily with SCH39304 at doses of 1 to 60 mg/kg of body weight or fluconazole at doses of 1 or 5 mg/kg of body weight. Amphotericin B was given intraperitoneally three times weekly, at doses of 3 or 6 mg/kg. After intracerebral challenge, SCH39304 prolonged survival in doses as low as 1 mg/kg, a dose at which fluconazole was ineffective. At equal doses, SCH39304 consistently increased survival more than did fluconazole but not longer than did amphotericin B. SCH39304 significantly lowered colony counts in brains more than did fluconazole but no more than did amphotericin B. SCH39304 was also superior to fluconazole after intranasal challenge at equal doses. SCH39304 appears to be superior to fluconazole in mice when the drugs are given at equal doses. Clinical trials are warranted.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Female; Fluconazole; Lung; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Saccharomyces cerevisiae; Spleen; Triazoles

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

Topics: Adolescent; Amphotericin B; Catheters, Indwelling; Cryptococcosis; Female; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritonitis

Topics: Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Meningitis

A 76-year-old man was admitted because of multiple nodular opacities in both lungs on chest X-ray. Cryptococcus was identified in the specimens obtained from bronchial brushing and bronchial washing. Primary pulmonary cryptococcosis was diagnosed as he had no underlying diseases and no foci in any other organs except the lung. Transbronchial injection (TBI) of amphotericin B was administered to the largest focus, in addition to the intravenous administration of miconazole. The chest tomogram 25 days after the first TBI showed marked decrease in the size of the largest focus, but no improvements were observed in other foci. TBI can be performed easily and safely, and perhaps more effectively than administration of amphotericin B with aerosol. This procedure may be of value in the treatment of pulmonary cryptococcosis.

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Injections, Intralesional; Lung Diseases, Fungal; Male

CSF studies of 14 cases of cryptococcus meningitis revealed: 1. Direct discerning of yeast cells in the blood cell counting chamber, by Indian ink stain, and by cytological examination based on Sayk's technic, all were highly positive in repeated examinations. 2. Morphology of cryptococcus and inflammatory cellular reactions in CSF were investigated, and were quite characteristic. 3. Suppression and destruction of yeast cells were attainable only when doses of amphotericin B were sufficient.

Topics: Adult; Amphotericin B; Child; Cryptococcosis; Female; Humans; Male; Meningitis; Middle Aged

We report a case of invasive cryptococcosis complicating continuous ambulatory peritoneal dialysis and its successful treatment. This form of infection has not been previously described.

Topics: Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Dose-Response Relationship, Drug; Humans; Lung Diseases

We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Flucytosine; Humans; Hyponatremia; Ketoconazole; Male; Meningitis; Middle Aged; Pancytopenia; Prognosis; Recurrence

Thirty six clinical isolates of Cryptococcus neoformans were tested for their susceptibility to 5-fluorocytosine and amphotericin B by the determination of minimum inhibitory concentrations and minimum fungicidal concentrations. 22.2% of the isolates were resistant to 5-fluorocytosine and 36.1% indicated 5-fluorocytosine tolerance. All strains were sensitive to amphotericin B.

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Drug Resistance, Microbial; Flucytosine; Humans

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Humans; Meningitis

We report a case of acute visual loss after a test dose (1 mg) of intravenous amphotericin B administered to a patient with systemic lupus erythematosus and with cryptococcal meningitis. Her visual acuity was normal prior to the injection of amphotericin B. The meningitis subsequently responded to miconazole and flucytosine treatment. Our findings suggest that amphotericin B should be withheld in the treatment of cryptococcal meningitis if disease of the optic nerve is strongly suspected.

Topics: Adult; Amphotericin B; Blindness; Cryptococcosis; Female; Humans; Lupus Erythematosus, Systemic; Meningitis

Topics: Amphotericin B; Cerebellar Ataxia; Cryptococcosis; Female; Humans; Meningoencephalitis; Middle Aged

Between 1979 and 1985, six of 26 patients undergoing continuous ambulatory peritoneal dialysis developed fungal peritonitis. All had received antibacterial therapy with cefamandole and/or netilmicin prior to the diagnosis. The causal organisms were Candida albicans (three), Candida glabrata (one), Cryptococcus laurentii (one) and Saccharomyces cerevisiae (one). Treatment comprised catheter removal preceded by antifungal drugs (flucytosine and/or amphotericin B) in four patients and catheter removal alone in two. All patients were transferred to haemodialysis and five of the six developed extensive intra-abdominal adhesions. The most prudent management of fungal peritonitis in children would seem to be early cannula removal.

Topics: Adolescent; Amphotericin B; Candidiasis; Child; Child, Preschool; Cryptococcosis; Female; Flucytosine; Humans; Kidney Transplantation; Male; Mycoses; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Renal Dialysis

A patient was admitted complaining of fever and headache. He was suspected of meningitis due to nuchal rigidity, and a lumbar puncture was performed. The patient was diagnosed as having cryptococcal meningitis, as Cryptococcus neoformans was found in an India ink preparation of the cerebrospinal fluid. Both amphotericin B and low-dose flucytosine (50 mg/kg/d) were concomitantly administered to the patient and his clinical symptoms improved. However, the combination therapy induced granulocytopenia and thrombocytopenia, which resolved after discontinuance of the drugs. Amphotericin B alone failed to cause granulocytopenia or thrombocytopenia. These results suggest that the mechanisms of granulocytopenia and thrombocytopenia may be toxic reactions to flucytosine in the azotemic state caused by amphotericin B. Our report emphasizes the need for clinicians to monitor for granulocytopenia and thrombocytopenia in patients receiving treatment with both amphotericin B and flucytosine, even when flucytosine is administered in a low dose.

Topics: Adult; Agranulocytosis; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Male; Meningitis; Thrombocytopenia

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Nervous System Diseases; Opportunistic Infections

Cryptococcal meningoencephalitis (CM) is a fatal disease if untreated. We have presented an unusual case of CM clinically diagnosed as transient ischemic attacks. Therapy with amphotericin B and flucytosine cured the infection and the patient had no further episodes of transient focal cerebral dysfunction. In patients with transient focal cerebral symptoms, study of the cerebrospinal fluid may prove helpful.

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Focal Infection; Humans; Ischemic Attack, Transient; Male; Meningoencephalitis; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Triazoles

Two patients with cryptococcal meningitis were treated with the investigational triazole drug fluconazole (UK-49,858). Cerebrospinal fluid (CSF) levels of fluconazole were between 3.0 and 5.4 mg/l 2 h after an oral dose of 50 mg daily in the first patient and between 7.9 and 9.0 mg/l after an oral dose of 100 mg daily in the second patient. These levels were in the same range as plasma levels. The first patient, a 46-year-old renal transplant patient, was both clinically and microbiologically cured after 28 weeks of therapy (follow-up 14 months). In the second patient, a 15-year-old girl with chronic mucocutaneous candidiasis, fluconazole led to clinical cure of the meningitis, but failed to eradicate cryptococci from the CSF. These cases illustrate that fluconazole is useful for the treatment of cryptococcal meningitis, especially when prolonged treatment is indicated as in patients with immunodeficiencies.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Cryptococcus; Female; Fluconazole; Humans; Male; Meningitis; Middle Aged; Triazoles

Topics: Amphotericin B; Animals; Antifungal Agents; Brain Diseases; Cryptococcosis; Female; Granuloma, Giant Cell; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Male; Polyethylene Glycols; Rats; Rats, Inbred Strains

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

Cryptococcal infection in man is widely disseminated and commonly involves the central nervous system. Primary bone involvement is rare. We report on 2 cases of localized cryptococcal osseous lesions treated successfully by surgery.

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Fluorescent Dyes; Humans; Osteitis; Radiography

Topics: Adult; Amphotericin B; Anemia, Aplastic; Cryptococcosis; Flucytosine; Humans; Male; Meningitis

We describe a patient who presented with cryptococcosis and the adult respiratory distress syndrome (ARDS) as the initial manifestation of the acquired immunodeficiency syndrome. This patient represents the first reported recovery from ARDS secondary to widespread cryptococcosis. He is currently doing well as an outpatient on maintenance therapy with amphotericin B and azidothymidine.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antiviral Agents; Cryptococcosis; Humans; Intubation, Intratracheal; Male; Radiography; Respiratory Distress Syndrome; Thymidine; Zidovudine

Topics: Amphotericin B; Cryptococcosis; Female; Humans; Kidney Failure, Chronic; Leukemia, Lymphocytic, Chronic, B-Cell; Meningitis; Middle Aged; Recurrence; Time Factors

Topics: Administration, Oral; Adolescent; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Injections, Intravenous; Meningitis; Middle Aged; Recurrence

The subacute onset of parkinsonism in a patient with cryptococcal meningoencephalitis is described. The prompt resolution of the extrapyramidal dysfunction with antifungal agents suggests direct involvement of basal ganglia structures by the cryptococcal infection. Rapid development of parkinsonism in immunocompromised individuals should prompt investigation for an infectious etiology.

Topics: Aged; Aged, 80 and over; Amphotericin B; Basal Ganglia Diseases; Cryptococcosis; Flucytosine; Humans; Male; Meningoencephalitis; Parkinson Disease

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Coccidioidomycosis; Cryptococcosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycoses

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Infant, Newborn; Infusions, Intravenous; Meningitis; Mycoses

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Opportunistic Infections

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Meningitis

A 33-year-old man was treated with systemic steroids for a retinal inflammatory lesion before the diagnosis of cryptococcal retinitis and meningitis was suspected. He died from central nervous system disease despite treatment with parenteral antifungals. Histopathological studies demonstrated ocular and disseminated systemic infection with Cryptococcus neoformans. Direct cryptococcal involvement of the eye is rare and is usually associated with disseminated disease. Systemic steroids must be used with caution, and patients who take these drugs require frequent monitoring.

Topics: Adult; Amphotericin B; Cryptococcosis; Flucytosine; Fundus Oculi; Humans; Male; Meningitis; Prednisone; Retina; Retinitis

Topics: Amphotericin B; Child; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Ilium; Osteomyelitis; Sacroiliac Joint

Topics: Amphotericin B; Aortitis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Male; Middle Aged

Topics: Agranulocytosis; Amphotericin B; Anemia, Hemolytic, Autoimmune; Cryptococcosis; Female; Flucytosine; Humans; Meningitis; Middle Aged; Neutropenia; Prednisolone; Purpura, Thrombocytopenic

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Flucytosine; Humans; Lung Diseases, Fungal; Male

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Administration Schedule; Follow-Up Studies; Humans; Meningitis; Recurrence

Combination pairs of 5-fluorocytosine (5-FC) + itraconazole (Itra), 5-FC + fluconazole (Fluc), and amphotericin B (Amph B) + Itra were administered to mice with experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis with a variety of combination ratios. The life-prolonging effect of the combinations was compared with the effect of each partner administered alone and with a double dosage. Using the U test of Mann and Whitney, the effects of the concentration were classified as synergistic, additive, indifferent or antagonistic; the degree of the interaction was compared with the known effect of Amph B and 5-FC combinations. The combination 5-FC + Itra was definitely synergistic or additive in candidiasis and aspergillosis. The most pronounced synergism occurred in the infection with a 5-FC-resistant strain of Candida albicans. The degree of synergism was the same as with 5-FC + Amph B. In cryptococcosis this combination was indifferent. The combination of 5-FC + Itra merits clinical investigation, especially in candidiasis and aspergillosis. Amph B + Itra was mostly indifferent and weakly antagonistic; the degree of antagonism was significantly weaker than the one observed with Amph B + ketoconazole (Keto). In candidiasis, 5-FC + Fluc was synergistic, but indifferent in cryptococcosis and aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Exophiala; Fluconazole; Flucytosine; Itraconazole; Ketoconazole; Mice; Mycoses; Triazoles

The efficacy of fluconazole, a new bis-triazole antifungal agent, was compared with that of orally administered ketoconazole and parenterally administered amphotericin B against aspergillus and cryptococcus infections in mice. Fluconazole was 5-20-fold more active than ketoconazole against systemic aspergillosis and against systemic, intracranial and pulmonary cryptococcosis but was less active than amphotericin B.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Brain Diseases; Cryptococcosis; Female; Fluconazole; Ketoconazole; Lung Diseases, Fungal; Mice; Opportunistic Infections; Triazoles

The authors report three cases of central nervous system cryptococcosis in children in the first decade of life, from Rio Grande do Sul State, Brazil. Diagnosis was supported by demonstration of Cryptococcus neoformans with India-ink preparations of the spinal fluid and Sabouraud's media culture. Clinical presentation included acute, subacute and chronic forms. Increased intracranial pressure and hydrocephalus were the complications during the course of the disease, and a ventriculoperitoneal shunt was used in one case. Undernutrition was associated with all cases and tubercle bacillus infection with one. Specific therapy was administered to the three patients. One patient was cured and the other two died.

Topics: Age Factors; Amphotericin B; Brain Diseases; Brazil; Cerebrospinal Fluid; Child; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Male; Meningoencephalitis

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Eosinophilia; Female; Flucytosine; Humans; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Male; Meningitis; Miconazole

Twenty cases of cryptococcal CNS infection treated at the Alfred and Fairfield Infectious Diseases Hospitals from 1975 to 1985 were reviewed. A predisposing immunological deficit was present in 40% of the cases and nearly half had evidence of pulmonary involvement. Severe headache was an almost universal presenting feature but fever and meningismus were not. Measurement of CSF cryptococcal antigen and CSF culture were far more reliable diagnostic markers than Indian ink smears. Cerebral CT scanning identified abnormalities in nearly 30% of cases, including 2 with cystic lesions and 2 with mass lesions. Combination therapy with amphotericin B and 5-fluorocytosine was used as first line treatment. Ventricular shunts were required for 2 patients with hydrocephalus, and persistently raised intracranial pressure often required frequent lumbar punctures and corticosteroids for control. Mortality was 30% and correlated with the presence of impaired conscious state, hydrocephalus or other neurological deficit, underlying immunodeficiency and low CSF glucose levels.

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Meningitis; Middle Aged; Prognosis; Risk Factors; Tomography, X-Ray Computed

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male

Generalized cryptococcosis with CNS involvement was diagnosed in a 3-year-old spayed German Shorthaired Pointer. Clinical findings included Horner's syndrome, generalized lymphadenopathy, temporal muscle atrophy, and chorioretinitis. Toxic epidermal necrolysis resulted after 19 days of treatment with 5-fluorocytosine and amphotericin B. After discontinuation of the 5-fluorocytosine and amphotericin B and treatment with cephradine and ketoconazole, the toxic epidermal necrolysis resolved. Treatment was completed without further complication by using amphotericin B and ketoconazole concurrently.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Flucytosine; Ketoconazole; Stevens-Johnson Syndrome

Fluconazole is a recently developed triazole with activity in vitro against Cryptococcus neoformans, water solubility, and excellent oral absorption. We compared fluconazole in murine cryptococcosis with ketoconazole and amphotericin B. Fluconazole was highly effective in suppressing cryptococcosis in mice challenged by the intravenous and intranasal routes, and was comparable with the other two drugs in its protective capacity. However, fluconazole was superior to ketoconazole and comparable with amphotericin B after intracerebral challenge. Fluconazole may warrant clinical evaluation in cryptococcosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Fluconazole; Ketoconazole; Kinetics; Meningitis; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Rats; Rats, Inbred Strains; Triazoles

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Humans; Ketoconazole; Lung Diseases, Fungal; Male; Meningitis

Cryptococcus neoformans is a major pathogen in patients with acquired immune deficiency syndrome and was found to infect 13.3 percent of such patients seen at two medical centers. Serum cryptococcal antigen levels were as high as 1:2,000,000 and, despite therapy, often remained elevated. Antigen titers in the cerebrospinal fluid generally declined at an expected rate in the survivors. The significance of high antigen titers in the blood after a prolonged course of therapy with amphotericin B and 5-flucytosine is unknown.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans

We present the findings in a patient having sickle cell disease who developed multilobar pneumonia. Cultures of bronchial aspirates and histologic specimens grew Cryptococcus neoformans. There was neither spontaneous clearing of the infection nor a response to bactericidal antibiotics. The patient had no underlying malignant neoplasm or immunodeficiency as indicated by history, physical examination, and specialized tests of humoral and cell-mediated immunity.

Topics: Adult; Amphotericin B; Anemia, Sickle Cell; Anti-Bacterial Agents; Cryptococcosis; Humans; Male; Pneumonia; Radiography

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Catheters, Indwelling; Cryptococcosis; Diagnosis, Differential; Fever of Unknown Origin; Humans; Liposomes; Mucormycosis; Mycoses; Neutropenia; Risk

In two AIDS patients (homosexual men) microscopical demonstration of Cryptococcus neoformans in samples obtained by puncture of the liver (n = 1) and additionally of the spleen (n = 1) led to the diagnosis of systemic cryptococcosis. Using the India ink method capsulated Cryptococcus neoformans cells could also be detected in cerebrospinal fluid (CSF) and urine. Concomitant culture of the fungus from tracheal secretion, CSF, urine and faeces confirmed the diagnosis of a disseminated infection; the identification and germ count of C. neoformans was achieved by means of the differential-selective medium Guizotia-abyssinica-creatinine agar. The C. neoformans antigen titres in serum and CSF corresponded to the stage of the mycosis as detected by microscopy and culture. After a six-week course of treatment with amphotericin B and flucytosine (Ancotil), the fungus could no longer be isolated from the materials examined in one patient. Mycological monitoring aiming at the detection of C. neoformans in the tracheal secretions by means of the mentioned differential-selective medium is therefore recommended as a prophylactic measure in AIDS patients and persons at risk.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male

A case of cryptococcal meningoencephalitis, as presented by a hypertensive hydrocephalus, is described. To our knowledge, this is the 24th case described in Italy since 1953. The diagnosis was made with ventricular fluid examination: the patient was successfully treated with amphotericin B and 5-fluorocytosine, thus avoiding the risks of surgical treatment of hydrocephalus. Early diagnosis and proper therapy are necessary in order to decrease the high lethality of cryptococcosis.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Meningoencephalitis; Tomography, X-Ray Computed

Intraventricular administration of amphotericin B for meningitis due to Cryptococcus neoformans is usually reserved for selected, seriously ill patients with recurrent disease. Between September 1973 and November 1983, 10 of 23 patients treated for cryptococcal meningitis at Memorial Sloan-Kettering Cancer Center received intraventricular amphotericin B through subcutaneous reservoirs, in addition to systemic therapy. The value of intraventricular amphotericin B was assessed in the 13 patients treated for first episodes of meningitis with systemic amphotericin B and flucytosine. Death during therapy occurred in one of six patients with intraventricular and systemic therapy compared with six of seven patients with systemic therapy alone (p = 0.025). The cerebrospinal fluid was sterilized in six of six patients given systemic and intraventricular therapy compared with three of seven given systemic therapy alone (p = 0.049), and the cerebrospinal fluid cryptococcal antigen titer declined in six of six patients given systemic and intraventricular therapy compared with two of seven given systemic therapy alone (p = 0.016). In the 10 patients who received intraventricular therapy, there were no complications related to reservoir insertion; however, complications related to reservoir use requiring replacement or revision occurred in two patients, and bacterial infection occurred in one but was treated successfully without removal of the reservoir. Although these data are retrospective, they suggest that early therapy with intraventricular amphotericin B in combination with systemic therapy may be beneficial and relatively safe in patients with cryptococcal meningitis and a poor prognosis.

Topics: Adult; Aged; Amphotericin B; Cerebral Ventricles; Cryptococcosis; Female; Humans; Infusions, Parenteral; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Humans; Lupus Erythematosus, Systemic; Meningitis

Between 1 January 1981 and 1 December 1984, 34 of 396 patients with the acquired immunodeficiency syndrome (AIDS) developed cryptococcal infections. Twenty-six cases are reviewed. Twenty-two patients had brain or meningeal disease; the others had pulmonary disease (2 patients), pericarditis (1 patient), and antigenemia (1 patient). During treatment, 3 patients died of cryptococcosis and 3 died of other causes. Fifteen patients were followed for more than 6 weeks after treatment. Of 8 patients who received no additional amphotericin B, 4 had relapses and died of cryptococcosis within 6 months, 3 died of other causes, and 1 survived. Of 7 patients who received maintenance therapy with amphotericin B, none had relapses, 3 died of other causes, and 4 survived. Our data suggest that maintenance therapy with amphotericin may be needed to prevent relapse in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Brain Diseases; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Injections, Intravenous; Injections, Intraventricular; Male; Meningitis; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Tomography, X-Ray Computed

Topics: Aged; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Immunosuppression Therapy; Male; Nephrotic Syndrome; Prednisone

The risk for AIDS patients from Cryptococcus neoformans is outlined on the basis of a case report on a 28-year old male patient whose disease was complicated by cryptococcosis. Beside the description of the diagnosis of cryptococcosis (demonstration of the agent and its antigen), epidemiological associations (habitat of Cr. neoformans in fecal matter of birds) and the clinically, mostly not recognized, route of infection via the lungs is stressed. The effective therapy with the combination of amphotericin B and 5-flucytosine, which also in this case has been successful is described from the clinical and microbiological angles. Finally, proposals for the prevention of Cr. neoformans infections in AIDS patients and for a special mycological surveillance directed at this fungus are made.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Male; Meningoencephalitis; Risk

Cryptococcal meningitis is a life-threatening disease. Headache, vomiting, cranial nerve symptoms and mental changes are the most common symptoms, but as many as 15% may have no symptoms referable to the CNS. For chemotherapy four drugs are available: namely amphotericin B, 5-fluorocytosine, miconazole and ketoconazole. Most cases have been treated by combination of amphotericin B and 5-fluorocytosine. The intrathecal administration of amphotericin B should be considered for patients who fail to respond to the usual intravenous therapy. The case is reported of a patient who died due to hydrocephalus, and the CSF-levels of the administered drugs are presented. Some pitfalls of therapy are discussed.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Resistance, Microbial; Drug Therapy, Combination; Flucytosine; Humans; Injections, Intraventricular; Male; Meningitis; Recurrence

Topics: Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Lung Diseases, Fungal; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome

Two patients with cryptococcal infection of the central nervous system are described. These cases illustrate the variability in mode of presentation of this disease. Upon diagnosis, both patients were initially treated with a combination of amphotericin B and 5-fluorocytosine. Despite an early clinical and serological response, limiting side effects occurred in both cases and 5-fluorocytosine treatment was terminated. In Case 2, 5-fluorocytosine therapy was reinstituted at lower dosages later in the course of the illness, with good results. Combination therapy is superior to amphotericin B alone. However, to circumvent significant toxicity problems close monitoring of renal function, peripheral blood counts and serum 5-fluorocytosine levels are essential. Treatment is usually administered for a minimum of six weeks and remission is assessed on clinical, mycological and serological grounds. Thereafter, adequate follow-up is mandatory.

Topics: Adult; Amphotericin B; Brain; Brain Diseases; Cryptococcosis; Flucytosine; Humans; Lung Diseases, Fungal; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Leukemia, Lymphoid; Middle Aged

Cryptococcus neoformans is a significant pathogen in immunosuppressed patients. In renal transplant recipients receiving prednisone, the development of cryptococcosis is associated with a poor prognosis. When such patients develop cryptococcosis they pose a particularly difficult clinical dilemma since withdrawal of prednisone, to facilitate cure of their fungal infection, may predispose to loss of their transplanted kidney. We report our experience with cryptococcal infection in 13 renal transplant patients. In 11 of these patients maintenance immunosuppression was cautiously continued to preserve allograft function. The results of our study suggest that maintenance immunosuppressive therapy may be continued throughout the period of antifungal therapy and does not preclude eradication of the infecting organisms. Our experience indicates that the prognosis for the renal transplant patient who has cryptococcosis can be improved.

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Immunosuppression Therapy; Kidney Transplantation; Prednisone

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Encephalitis; Flucytosine; Humans; Meningitis; Retrospective Studies; Serologic Tests

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

A recurrence of cryptococcosis sixteen years after the primary infection as a penile ulcer is reported. The clinical manifestations of genitourinary and skin involvement by cryptococci are discussed. The epidemiology, pathogenesis, diagnosis, and treatment of penile mycotic infections are reviewed.

Topics: Amphotericin B; Cryptococcosis; Humans; Male; Middle Aged; Penile Diseases; Recurrence

Skeletal cryptococcosis is an uncommon infection. Isolated osteomyelitis due to Cryptococcus neoformans is quite rare. Only seven cases of skeletal cryptococcosis with involvement of vertebrae but no systemic infection have been reported. In only one was there paraplegia. Since vertebral cryptococcosis seems not to have been reported previously in Japan, this case of a 50-year-old coal miner successfully treated for paraparesis caused by cryptococcal spondylitis of the ninth, tenth, and 11th thoracic vertebrae is noteworthy. Two decompression operations and combined amphotericin B and flucytosine therapy reduced the patient's paraparesis, and no sign of recurrence was seen for 21 months after the second operation.

Topics: Amphotericin B; Combined Modality Therapy; Cryptococcosis; Flucytosine; Humans; Male; Middle Aged; Muscle Spasticity; Osteomyelitis; Paraplegia; Thoracic Vertebrae; Time Factors

Cryptococcosis is a systemic fungal disease and meningitis is the most serious complication. The purpose of this study is to define problems related to its diagnosis and treatment. This is a retrospective analysis of 25 patients admitted from January 1978 to December 1981. All patients had cryptococcal neoformans meningitis proven by culture of cerebrospinal fluid. One patient had a predisposing illness, being on immunosuppressant therapy after a renal transplant 2 years ago. A progressively severe headache of recent onset was the most striking presentation. Fever was frequently absent as a symptom. Cranial nerve palsies were commonly seen. Impairment of consciousness and areflexia signified a poor prognosis as all four patients who died early in the course of treatment were comatose and two of them were areflexic on admission. In newly suspected cases at least 3 separate lumbar punctures are recommended as initial smears or cultures may be negative. Cerebral CT scans were abnormal in 12 patients and those with cerebral oedema or hydrocephalus had a poorer prognosis. Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice. If there is no relapse 3 years after completion of treatment, patients are considered as cured. Positive smears may remain for years after completion of treatment and retreatment is only indicated if the cultures are positive. Twenty patients are alive today and none of them have relapsed. One patient had vasculitis of both anterior cerebral arteries as a result of cryptococcal meningitis.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Cryptococcosis; Flucytosine; Follow-Up Studies; Garlic; Humans; Ketoconazole; Meningitis; Miconazole; Middle Aged; Plant Extracts; Plants, Medicinal

A patient presented with a bilateral profound hearing loss of sudden onset following a two-month neurologic illness. Microscopy and culture of cerebrospinal fluid revealed Cryptococcus neoformans. Treatment with amphotericin B and 5-fluorocytosine failed to restore hearing. Auditory brain stem response and electrical promontory stimulation suggest a profound deafness with poor neuronal survival. This is consistent with previous temporal bone histopathology reports in individuals dying of cryptococcal meningitis, suggesting a retrocochlear lesion. It is important to exclude this occult pathologic factor in a patient with the sudden onset of sensorineural deafness prior to embarking upon a course of steroid therapy.

Topics: Amphotericin B; Audiometry, Evoked Response; Cryptococcosis; Electronystagmography; Evoked Potentials, Auditory; Female; Flucytosine; Hearing Loss, Sudden; Humans; Meningitis; Middle Aged

The acquired immune deficiency syndrome (AIDS) has reached epidemic proportions in the USA and the incidence of this potentially fatal viral infection is increasing rapidly in Australia. The loss of normal cellular immunity in affected individuals predisposes them to severe opportunistic infections and neoplasms, especially Kaposi's sarcoma. Both of these pathological processes may affect the eye, and ocular involvement with an opportunistic infection or malignancy may be the first clue to the presence of AIDS. We present here the first Australian report of a patient with AIDS presenting with ocular involvement. The case is discussed in relation to current concepts of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Candidiasis, Oral; Cryptococcosis; Eyelid Neoplasms; Flucytosine; Humans; Male; Sarcoma, Kaposi; Vinblastine

Cryptococcus neoformans (Torula histolytica) is an uncommon cause of infection in the central nervous system. We review 15 cases from all over Queensland which have presented in the last 6 years. Computed tomography (CT) studies were abnormal in 73.5%, with mass lesions and hydrocephalus being the commonest findings. Notable findings were: the disproportionate severity of clinical signs and symptoms as compared with the CT findings, which often were either normal or demonstrated only small granulomas without significant mass effect, absence of enhancement in granulomas in two cases and observation of calcification during treatment in one patient.

Topics: Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Brain Neoplasms; Cryptococcosis; Diagnosis, Differential; Female; Humans; Immune Tolerance; Male; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Tomography, X-Ray Computed; Tuberculosis, Meningeal

Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experiments. N-D-ornithyl amphotericin B methyl ester gave a slightly higher concentration in serum than amphotericin B did, but both drugs had similar elimination curves, and penetration into the cerebrospinal fluid was poor for both. Despite these similarities between the two polyenes, amphotericin B was much more effective than N-D-ornithyl amphotericin B methyl ester in the treatment of cryptococcal meningitis in rabbits. For C. albicans endocarditis, both polyenes had similar cure rates, but in vitro measurement of fungicidal activity in serum did not predict treatment outcome. For C. albicans pyelonephritis, both polyenes showed efficacy; because higher doses of the less toxic methyl ester could be used, it sterilized the urinary tract more often than amphotericin B. These studies indicate that in vivo and in vitro experiments may be needed to predict the results of treatment with polyenes.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cryptococcosis; Endocarditis; Kinetics; Meningitis; Microbial Sensitivity Tests; Mycoses; Pyelonephritis; Rabbits; Yeasts

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Ketoconazole; Male; Meningoencephalitis; Miconazole; Prognosis

Current therapy for cryptococcal meningitis often is ineffective, toxic, and inconvenient. Ketoconazole has been shown to penetrate into brain tissue of mice and cerebrospinal fluid of humans and to improve the course of human coccidioidal meningitis. Ketoconazole, flucytosine, and amphotericin B, alone and in two-drug combinations, were used to treat cryptococcal meningitis in mice injected intracranially with Cryptococcus neoformans. Mortality was assessed, and numbers of cryptococci in brain and liver were counted. By both of these parameters, the combination of flucytosine and ketoconazole produced results superior to those of either agent used alone. The standard combination of amphotericin B and flucytosine also showed an additive effect in this model. However, the combination of amphotericin B and ketoconazole consistently showed no additive effect. None of the combinations of drugs was antagonistic. Our results indicate a possible role for therapy with a combination of oral flucytosine and ketoconazole as part of the treatment for cryptococcal meningitis.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Cytosine; Drug Synergism; Drug Therapy, Combination; Female; Flucytosine; Ketoconazole; Male; Meningitis; Mice; Mice, Inbred BALB C

Topics: Amphotericin B; Animals; Cryptococcosis; Drug Therapy, Combination; Immunosuppression Therapy; Ketoconazole; Lung Diseases, Fungal; Male; Mice

The triazole derivative BAY N 7133 has been tested for its antimycotic efficacy on oral administration in vivo and compared with ketoconazole in mice infected with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans and in guinea pig trichophytosis. On starting administration at the same time as infection and using daily doses between 25 and 100 mg/kg, the agent protected the mice in all experimental models, even mouse aspergillosis for which ketoconazole was not adequately effective. BAY N 7133 was also effective for mouse candidosis by parenteral administration and was effective for guinea pig trichophytosis on topical application.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Female; Flucytosine; Guinea Pigs; Hair; Infusions, Parenteral; Ketoconazole; Male; Mice; Mycoses; Triazoles

Patients with the hyperimmunoglobulin E-recurrent infection (Job's) syndrome, which is characterized by an elevated immunoglobulin E level, recurrent staphylococcal infections, and an abnormality of neutrophil chemotaxis, have been reported to have visceral Candida infections in addition to their more frequent pyogenic infections. We report a patient with Job's syndrome who presented with massive hematemesis secondary to esophageal cryptococcosis. A thorough evaluation for an occult neoplasm or extraesophageal cryptococcosis was negative. The patient received a 6-wk course of amphotericin B (970 mg) and 5-fluorocytosine with complete radiographic and endoscopic resolution of the lesion. He is doing well 18 mo after therapy. The patient was not anergic, and his response to T-cell mitogens, helper-to-suppressor T-cell ratio, total number of T cells, and immunoglobulin-producing capability were all normal. This case is unusual in that it is the first documentation of a cryptococcoma of the esophagus and underscores the importance of culturing abnormal specimens for unsuspected pathogens in unusual clinical circumstances.

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Endoscopy; Esophageal Diseases; Flucytosine; Humans; Job Syndrome; Male; Phagocyte Bactericidal Dysfunction

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Obesity

Topics: Adult; Amphotericin B; Blastomycosis; Coccidioides; Coccidioidomycosis; Cryptococcosis; Estradiol; Female; Flucytosine; Humans; Lung Diseases, Fungal; Pregnancy; Pregnancy Complications, Infectious; Risk; Stimulation, Chemical; United States

The effect of amphotericin B on magnesium metabolism was studied in 10 patients (aged 30 to 68 years) with systemic fungal infections. Renal magnesium wasting resulting in mild to moderate hypomagnesemia was demonstrated by the second week of therapy following relatively small cumulative dosages of amphotericin B (208 +/- 40 mg). The lowest serum levels and largest fractional excretions of magnesium were observed by the fourth week of therapy after cumulative dosages of 510 +/- 118 mg. A plateauing of the renal magnesium wasting is suggested, as there were no further increases or reductions in fractional magnesium excretion and serum magnesium level, respectively, despite continued amphotericin B administration. Reversibility of the magnesium wasting is indicated by data in three of the patients approximately one year following discontinuation of amphotericin B therapy, in whom the serum magnesium level and fractional magnesium excretion had returned to pretreatment baseline values. Although the available data do not allow precise localization of this defect, increased urinary excretion of magnesium despite its reduced filtered load suggests a tubular defect in magnesium reabsorption. Therefore, routine monitoring of the serum magnesium level during treatment with amphotericin B is recommended.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Candidiasis; Coccidioidomycosis; Creatinine; Cryptococcosis; Female; Humans; Magnesium; Male; Middle Aged; Prospective Studies

Previous reports have emphasized that cryptococcemia is almost uniformly fatal. To define the clinical course and prognostic and therapeutic implications of cryptococcemia, we studied 15 patients treated at this medical center over the past 7 years. Cryptococcemia was strongly associated with corticosteroid therapy, especially when the dosage had recently been increased. Meningitis was common (but not invariably present) in these patients, characteristically with a large burden of organisms in the cerebrospinal fluid. Cryptococcemia developed during hospitalization in one-third of our patients; this high rate of nosocomial infection emphasizes that C. neoformans infection should be considered in febrile, immunocompromised patients even when the initial work-up is negative. Most of these patients were treated with amphotericin B plus 5-fluorocytosine. Although the one-year survival rate of 4/15 (29%) was dismal, no patient died from uncontrolled cryptococcal infection. Other infections, which developed before, during or after cryptococcemia was diagnosed, were the major immediate cause of morbidity and mortality. The progress of underlying diseases and the outcome of concomitant infections in these patients were more important determinants of survival than was cryptococcemia itself.

Topics: Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Host-Parasite Interactions; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prognosis

Four patients with fungal meningitis and hydrocephalus were treated by placement of intraventricular shunts prior to the diagnosis of infection. As a consequence, they were subjected to the risks of surgery as well as to shunt suprainfection. We suggest that chronic meningitis be ruled out in all patients prior to placement of shunts. Preoperative evaluation should include the examination of cisternal or ventricular CSF when a lumbar CSF specimen is nondiagnositc. When fungal meningitis is present, a course of amphotericin B should be initiated and the CSF sterilized prior to the placement of the permanent extracranial shunt. Where acute hydrocephalus supervenes, temporary ventricular drainage may be employed. In some cases of fungal meningitis, the symptoms of hydrocephalus will be resolved with antifungal therapy alone, obviating the need for ventricular decompression.

Topics: Adult; Amphotericin B; Blastomyces; Blastomycosis; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Humans; Hydrocephalus; Male; Meningitis; Middle Aged; Mycoses; Staphylococcal Infections; Staphylococcus; Time Factors

Little information is available regarding the in-vivo effects of amphotericin B on organs other than the kidney. The increasing use of intrathecal amphotericin B has resulted in several reports of neurotoxicity associated with the drug. Development of parkinsonism following intraventricular treatment with amphotericin B for cryptococcal meningitis in a young woman suggested a direct toxic effect on nervous tissue by amphotericin B. Although transient signs of parkinsonism have been described in a patient receiving intraventricular amphotericin B, persistent parkinsonism is an unprecedented occurrence.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Injections, Intraventricular; Meningitis; Parkinson Disease, Secondary

Topics: Aged; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Meningoencephalitis

The incidence of clinically manifest cryptococcosis was determined among over one million subscribers to the Kaiser-Permanente Medical Care Program in Northern California during the 10-year period 1971-1980. A total of 10 persons developed the disease, of whom two had no underlying immunosuppressive disease or therapy. The overall incidence was 0.8 per million persons per year; for nonimmunosuppressed individuals the incidence was estimated to be 0.2 per million per year. Incidence increased with age into the seventh decade of life and was greater in men than in women. The overall case fatality rate was 40 per cent. The data are not consistent with the view that cryptococcosis usually occurs in persons without obvious predisposing factors.

Topics: Adult; Age Factors; Aged; Amphotericin B; California; Cryptococcosis; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Sex Factors

Ketoconazole, amphotericin B, 5-fluorocytosine, and combinations of these drugs were compared as therapy for chronic cryptococcal meningitis in steroid-treated rabbits. Two hours after treatment of rabbits with meningitis with single drugs the mean cerebrospinal fluid concentration of 5-fluorocytosine was 4.4 microgram/ml, that of amphotericin B was less than 0.3 microgram/ml, and that of ketoconazole ranged from less than 0.2 to 0.8 microgram/ml. Serial quantitative cultures indicated that amphotericin B was the best single-drug regimen. Ketoconazole provided little or no additive effect when used in combination with fluorocytosine or therapeutic doses of amphotericin for two weeks. However, the combination of ketoconazole plus amphotericin B was at least as effective as amphotericin B plus 5-fluorocytosine over a two-week treatment regimen. The addition of ketoconazole to subtherapeutic dose of amphotericin B significantly increased the killing of cryptococci in cerebrospinal fluid.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Cytosine; Drug Synergism; Drug Therapy, Combination; Flucytosine; Imidazoles; Ketoconazole; Male; Meningitis; Piperazines; Rabbits

Combination pairs of the major systematic antimycotic drugs, amphotericin B (AmphB), 5-fluorocytosine (5-FC) and ketoconazole (Ktz) were administered to mice with experimental candidiasis, cryptococcosis and aspergillosis at a variety of combination ratios. The 3 mycoses were produced with 3 strains each of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, respectively, which were preselected to represent 3 different degrees of 5-FC sensitivity ('normally sensitive', 'moderately resistant', and 'definitely resistant'). The life-prolonging effect of the combinations was compared with the effect of each partner administered alone at the same and at the double dosage. Using the U test of Mann and Whitney and setting limits which on the whole were more rigorous than those of the isobole methods commonly applied to the study of drug interactions, the effects of the concentrations were classified as 'synergistic', 'additive', 'indifferent' or 'antagonistic'. The combination AmphB plus 5-FC was definitely synergistic or definitely additive in all 3 candidiasis models, the most pronounced synergism occurring in the infection with the 'definitely 5-FC-resistant' C. albicans strain; in cryptococcosis produced by any of the 3 C. neoformans strains the effect was definitely additive, but only slightly additive or indifferent in the 3 aspergillosis models. The combination AmphB plus Ktz was slightly synergistic in candidiasis produced by one C. albicans strain, but definitely antagonistic in this mycosis produced by the remaining 2 strains of the same species; the combination was definitely additive or, even, slightly synergistic in the 3 cryptococcus models, but, again, antagonistic in aspergillosis produced by all 3 strains of A. fumigatus. 5-FC plus Ktz was additive or indifferent in the 3 candidiasis models, but throughout indifferent in cryptococcosis and aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Imidazoles; Ketoconazole; Male; Mice; Piperazines

A 63-year-old man presenting with acute retention and dysuria underwent transurethral resection of the prostate for suspected benign prostatic hypertrophy. Ten days postoperatively he developed disseminated cryptococcosis. Re-examination of the prostatic chips revealed cryptococcal prostatitis. Treatment consisted of amphotericin, flucytosine and transfer factor along with wedge resection of a pulmonary toruloma. He remains well 12 months after cessation of treatment. This appears to be the first case report in Australia of cryptococcal prostatitis with dissemination after transurethral resection of the prostate.

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Lung Diseases, Fungal; Male; Middle Aged; Prostatectomy; Prostatitis; Transfer Factor; Urethra

This study is a review of cryptococcal meningitis in Queensland, Australia, with particular reference to changes in incidence, methods of diagnosis and treatment and their effects on mortality and morbidity over the past three decades. Cryptococcal meningitis remains more prevalent among males, and aborigines. Mortality has declined dramatically since 1948, due to the use of the specific antifungal agents amphotericin B, flucytosine, and more recently miconazole. The availability of cranial computerized axial tomography and the early treatment of hydrocephalus have significantly contributed to the overall management of these patients. 75% of patients receiving a full course of treatment can now be expected to make a satisfactory recovery.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antigens, Fungal; Australia; Child; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Ethnicity; Female; Flucytosine; Follow-Up Studies; Humans; Male; Meningitis; Miconazole; Middle Aged; Tomography, X-Ray Computed

The findings and opinions which are of greater importance for clinical practice with respect to the etiopathogenesis, epidemiology, symptomatology, diagnostics and therapy of cryptococcosis of the central nervous system are discussed with special consideration of the cerebrospinal fluid findings and in evaluation of two cases treated by the authors. Crytococcosis of the CNS produces no clinical pictures that are only typical of it. Favourable curing changes, however, only exist if a specific therapy is initiated systematically and at an early time, for which the application of a combination of amphotericin B and 5-fluorocytosin is considered as the therapy of first choice today. Hints are given that should make an inclusion of cryptococcosis in the differential-diagnostic consideration possible.

Topics: Amphotericin B; Bacteriological Techniques; Cryptococcosis; Diagnosis, Differential; Flucytosine; Humans; Male; Meningitis; Meningoencephalitis; Middle Aged; Myelitis; Prognosis

A case is reported of isolated cryptococcal osteomyelitis in an 11-year-old girl without any detectable underlying disease. The patient was successfully treated for six weeks with intravenous amphotericin B and oral 5-flucytosine. There is only one other case of cryptococcal osteomyelitis reported in the English medical literature in a child. Over 50 per cent of individuals with this infection will have an underlying condition which may have predisposed them to acquiring this disease.

Topics: Amphotericin B; Child; Cryptococcosis; Female; Flucytosine; Humans; Osteomyelitis

Liposomes were prepared to incorporate large amounts of amphotericin B. BALB/c mice were challenged with Cryptococcus neoformans and given liposome-associated amphotericin B (AMBL) or amphotericin B-deoxycholate (AMBD) intravenously. Mice that were treated with AMBL survived longer and had lower tissue counts of cryptococci than mice treated with AMBD or untreated control mice. The reduced acute toxicity of AMBL permitted much larger doses of amphotericin B to be given than were possible with AMBD. AMBL is a novel vehicle of administration that reduces toxicity and concentrates the drug in the appropriate target organs.

Topics: Amphotericin B; Animals; Cryptococcosis; Female; Liposomes; Male; Mice; Mice, Inbred BALB C

Topics: Amphotericin B; Animals; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Horse Diseases; Horses; Male; Meningitis

Flucytosine-associated diarrhea has been previously described in 6%-10% of patients receiving the drug. A potentially fatal ulcerating enterocolitis has been reported in 4 patients. In none of these reports has radiologic or pathologic data been presented. This report describes a case of flucytosine-associated ulcerating enteritis in which the small bowel x-ray demonstrated severe luminal narrowing, ulceration, and marked separation of loops of bowel. Ileal biopsy revealed an erosive enteritis with mucosal inflammatory infiltrate and disruption of the surface epithelium. Discontinuation of the drug resulted in total resolution of the clinical and radiologic abnormalities.

Topics: Aged; Amphotericin B; Biopsy; Cryptococcosis; Cytosine; Diarrhea; Flucytosine; Humans; Ileitis; Ileum; Male; Radiography; Ulcer

Topics: Adult; Amphotericin B; Brain Diseases; Cryptococcosis; Cytosine; Flucytosine; Humans; Male; Meningitis

Topics: Adult; Amphotericin B; Basal Ganglia; Cryptococcosis; Female; Flucytosine; Humans; Male; Meningoencephalitis; Tomography, X-Ray Computed

The first documented cure of cryptococcosis with cryptococcemia is reported. The patient had systemic lupus erythematosis and had received corticosteroids and immunosuppressive drugs for diffuse proliferative nephritis. She had additional poor prognostic factors including high serum cryptococcal antigen titer, low cerebrospinal leukocyte count, and absence of anticryptococcal antibody. Pulmonary tuberculosis was diagnosed concurrently and subsequently she developed disseminated herpes zoster. During amphotericin B therapy, renal function worsened. Cure of cryptococcosis with cryptococcemia was accomplished despite multiple concurrent infections and transient worsening of renal function.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Nephritis; Pneumonia, Viral; Tuberculosis, Pulmonary

A case of granulomatous prostatitis due to Cryptococcus neoformans is reported. The patient, who had a history of diabetes mellitus and chronic active hepatitis, had symptoms of prostatic hypertrophy. Tissue obtained from surgery showed granulomatous prostatitis, and a cryptococcal organism was identified by special stains. Postoperative cultures grew Cryptococcus neoformans, and the patient was treated successfully with surgery and a short course of amphotericin B. After nine months of follow-up, there is no evidence of systemic infection.

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Diabetes Complications; Hepatitis, Alcoholic; Humans; Male; Middle Aged; Prostatectomy; Prostatitis

Topics: Adrenal Cortex Hormones; Amphotericin B; Asthma; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Meningitis; Middle Aged; Prednisone

The authors present one case of cutaneous cryptococcosis, which diagnosis was confirmed by histopathologic and mycologic procedures. As there has not been systemic dissemination, this case must be considered uncommon. The lesions healed completely after treatment by amphotericin-B.

Topics: Amphotericin B; Cryptococcosis; Dermatomycoses; Humans; Male; Middle Aged; Skin

Topics: Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Female; Flucytosine; Humans

Topics: Aged; Amphotericin B; Antibodies, Fungal; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Meningitis

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis; Middle Aged

We have described a case of Cryptococcus neoformans endophthalmitis, especially rare in the absence of simultaneous CNS involvement. The key to management appears to lie in early diagnosis, which is difficult because there are multiple causes of uveitis; clinical examination will not establish the specific cause. If clinical improvement is not apparent after several days of nonspecific therapy and other studies have failed to yield a diagnosis, appropriate stains and cultures of vitreal aspirate should be done for fungi and other organisms. Amphotericin B plus 5-fluorocytosine is the treatment of choice, possibly with intravitreal instillation of amphotericin B and vitrectomy.

Topics: Amphotericin B; Cryptococcosis; Eye Diseases; Female; Flucytosine; Humans; Middle Aged

Two cases of crytococcal meningitis occurred in pregnancy. Amphotericin B was administered in the first trimester in one case, and amphotericin B and flucytosine (5-fluorocytosine) were administered in the second trimester in the second. Both cases had good fetal and maternal outcome. Combined therapy for cryptococcal infections in pregnancy is discussed.

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Meningitis; Pregnancy; Pregnancy Complications, Infectious

Topics: Adult; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Female; Flucytosine; Humans; Meningitis; Tuberculosis, Meningeal

Pulmonary infection with Cryptococcus laurentii occurred in a patient with dermatomyositis receiving corticosteroid therapy. Infections with cryptococci other than C. neoformans are rare, and pulmonary involvement with C. laurentii has not been reported previously. The isolate was susceptible to amphotericin B but resistant to 5-fluorocytosine, and synergism could not be demonstrated with these 2 drugs. Amphotericin B without surgical resection, concurrent with reduction in the dosage of corticosteroids, resulted in clinical and roentgenogrphic resolution of the infection.

Topics: Adrenal Cortex Hormones; Amphotericin B; Cryptococcosis; Female; Humans; Lung Abscess; Middle Aged; Radiography

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Injections, Spinal; Meningitis; Prognosis

A 50-year-old woman with cryptococcal meningitis was treated with amphotericin B intrathecally through a Rickham reservoir and intravenously, together with flucytosine orally. After 4 months of treatment cryptococci and cryptococcal antigen were still present in cerebrospinal fluid from time to time. After removal of the Rickham reservoir the patient recovered completely within 6 weeks. The persistent infection was thus found to be due to the presence of the Rickham reservoir, a complication to intrathecal therapy which has not been reported before.

Topics: Amphotericin B; Catheterization; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Injections, Intravenous; Injections, Intraventricular; Injections, Spinal; Injections, Subcutaneous; Meningitis; Middle Aged; Recurrence

A case of an intrathecal cryptococcal granuloma in the cauda equina is reported. Successful and minimally toxic therapy with intrathecal amphotericin B and oral 5-fluorocytosine, preceded by surgery, is described.

Topics: Adolescent; Amphotericin B; Cauda Equina; Cryptococcosis; Flucytosine; Granuloma; Humans; Injections, Spinal; Male; Spinal Cord Diseases

A patient with unexplained lung abscess six years previously, developed chronic meningitis, and later, bilateral chorioretinitis. The organism found was Cryptococcus neoformans. The patient was successfully treated with amphotericin B and 5-fluorocytosine.

Topics: Adult; Amphotericin B; Cryptococcosis; Eye Diseases; Female; Flucytosine; Humans; Lung Abscess

A retrospective review of cryptococcal meningitis in Papua New Guinea adults showed that the condition is at least as common as tuberculous meningitis. The majority of the patients were young and all were previously healthy. A mortality rate of more than 50% was observed despite amphotericin B therapy. Cryptococcal aetiology should be suspected and looked for in every patient with chronic meningitis in Papua New Guinea. Examining the cerebrospinal fluid for cryptococcal antigen is of value when Indian ink smear and culture are negative.

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Female; Humans; Male; Meningitis; Middle Aged; New Guinea; Retrospective Studies; Tuberculosis, Meningeal

Minocycline has an additive anticryptococcal effect when combined with amphotericin B in vitro, and the combination lowers tissue counts of fungi. However, minocycline offers no survival benefit to amphotericin B therapy in murine cryptococcosis.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Therapy, Combination; Female; Male; Mice; Minocycline; Tetracyclines

A case of cryptococcal meningoencephalitis occurrying in a 26-year-old white man disclosing clinical as well radiological features of a expanding process localized in the right cerebral hemisphere is reported. A definitive diagnosis was established through histopathologic examination following right fronto-temporo-parietal exploratory and decompressive craniotomy. Cryptococcus neoformans was easily demonstrated in the leptomeninges as well as in cystic spaces in the brain substance.

Topics: Adult; Amphotericin B; Biopsy; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Humans; Male; Meningoencephalitis

Topics: Amphotericin B; Cryptococcosis; Cytosine; Flucytosine; Humans; Kidney Transplantation; Male; Middle Aged; Peritoneal Dialysis; Transplantation, Homologous

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Antigens, Fungal; Child; Collagen Diseases; Cryptococcosis; Female; Flucytosine; Hodgkin Disease; Humans; Ireland; Latex Fixation Tests; Male; Middle Aged; Neoplasms; Sarcoidosis; United Kingdom

Topics: Amphotericin B; Cryptococcosis; Granuloma; Humans; Lung Diseases; Male; Middle Aged; Radiography

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Male; Meningitis; Middle Aged

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

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Infusions, Parenteral; Time Factors

A 31-year-old woman with long-standing renal disease, treated with systemic steroids and azathioprine, developed progressive skin ulceration and subcutaneous nodules. A diagnosis of cryptococcosis was established after histological examination of a cutaneous lesion and confirmed by culture of the organism from the biopsy specimen. A detailed description of the histology and ultrastructure of the cutaneous lesion is presented. Treatment with parenteral amphotericin B and 5-fluorocytosine resulted in dramatic resolution of the skin lesions.

Topics: Adult; Amphotericin B; Cryptococcosis; Dermatomycoses; Drug Therapy, Combination; Female; Flucytosine; Humans; Skin

Topics: Amphotericin B; Cryptococcosis; Humans; Injections, Intravenous; Male; Meningitis; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation; Flucytosine; Humans; Meningitis; Miconazole

Serious therapeutic problems are posed by the increasing incidence of invasive fungal infections in transplant recipients as well as in patients with compromised immune defenses, prosthetic devices and grafts and several other predisposing factors. A number of new approaches, including combination drug treatment and the development of newer agents, may justify increased optimism in the management of these infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Immunity; Kidney Transplantation; Miconazole; Mycoses

Topics: Aged; Amphotericin B; Chronic Disease; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Female; Flucytosine; Humans; Immunoglobulin G; Meningoencephalitis

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

Topics: Amphotericin B; Cervical Vertebrae; Cryptococcosis; Flucytosine; Humans; Infant; Male; Osteomyelitis

A 17-year old girl received prednisone and azathioprine for the treatment of systemic lupus erythematosus. She developed a fever and hallucinations 18 months later; cryptococcal meningitis was diagnosed. An internal ophthalmoplegia with loss of accommodation and dilation of the pupils developed together with bilateral lateral rectus palsy. Treatment with intravenous amphotericin resulted in disappearance of papilledema, muscle palsy, and internal ophthalmoplegia. We believe that the internal ophthalmoplegia was secondary to involvement of the accommodative and pupillary fibers of both third nerves at the base of the brain.

Topics: Adolescent; Adult; Aged; Amphotericin B; Azathioprine; Child; Child, Preschool; Cryptococcosis; Female; Humans; Lupus Erythematosus, Systemic; Male; Meningitis; Middle Aged; Ophthalmoplegia; Papilledema; Prednisone

Topics: Administration, Oral; Amphotericin B; Animals; Cat Diseases; Cats; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Injections, Intravenous

Topics: Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Meningitis

Topics: Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Meningitis

The new therapeutic methods based on antibiotics, corticosteroids and immunosuppressors and the new medicosurgical techniques (catheters, monitoring in intensive-care units, open-heart surgery) modify the host, favorise the adaptation and introduction f endogenous and exogenous yeast-like fungi and thus create a new pathology characterized by deep visceral or septicemic infections due to yeasts belonging to the genera Candida, Torulopsis, Cryptococcus, Trichosporon, Rhodotorula, and Saccharomyces. The pathological aspects are analyzed and therapy is suggested in the light of new findings on polyenes (nystatine, amphotericine B), 5-fluorocytosine, imidazole, derivatives (miconazole, econazole) considering their association in function of synergy or antagonism possibilities.

Topics: Amphotericin B; Candida; Candidiasis; Cryptococcosis; Dermatomycoses; Endocarditis; Flucytosine; Humans; Iatrogenic Disease; Imidazoles; Lung Diseases, Fungal; Mycoses; Nystatin; Osteitis; Sepsis; Urinary Tract Infections

Topics: Amphotericin B; Child; Cryptococcosis; Female; Humans; Kidney Transplantation; Transplantation, Homologous

Topics: Adult; Aged; Amphotericin B; Corneal Transplantation; Cryptococcosis; Endophthalmitis; Female; Flucytosine; Humans; Postoperative Complications; Tissue Donors; Transplantation, Homologous

Miconazole was compared with amphotericin B in the treatment of murine cryptococcosis. Both subcutaneous and intraperitoneal administration of miconazole produced serum levels higher than the minimum inhibitory concentration for the challenge strain. However, maximal tolerable doses of miconazole gave no increase in survival. When combined with amphotericin B, miconazole demonstrated neither additive nor antagonistic effects on survival. Spleen and brain counts of cryptococci were not lowered by miconazole; also, miconazole did not alter the effect of amphotericin B on reducing tissue counts. In vitro studies confirmed that the strain of Cryptococcus neoformans was quite susceptible to both miconazole and amphotericin B. However, miconazole had a delayed onset of antifungal activity. This was apparent even at miconazole levels 20 times greater than the minimum inhibitory concentration. Also, the antifungal activity of miconazole was markedly inhibited by serum. Delayed antifungal activity and serum inhibition may limit the in vivo effectiveness of miconazole in murine cryptococcosis.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Imidazoles; Male; Mice; Mice, Inbred BALB C; Miconazole; Microbial Sensitivity Tests

Congenitally athymic nude (nu/nu) and thymus-containing heterozygous (nu/X) mice were infected intraperitoneally with Cryptococcus neoformans over a wide range of challenge doses. Cryptococcal disease progressed more rapidly in nude mice than in their nu/X littermates. When nu/X mice were treated with amphotericin B, all survived an otherwise lethal dose of C. neoformans. At larger challenge doses, survival was prolonged in nu/nu mice treated with amphotericin B, but they later succumbed to cryptococcosis. At lower challenge doses, amphotericin B was curative in some nude mice. Therapy of nude mice with both amphotericin B and flucytosine further prolonged survival at high-dose challenge and increased the number of cures at low-dose challenge. These studies support an interaction of antifungal chemotherapy with thymus-dependent immune defense mechanisms. This interaction is most evident at high challenge doses, where antifungal chemotherapy cures nu/X mice but only modestly prolongs survival in nude mice.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Immunity, Cellular; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microbial Sensitivity Tests

Nosocomial Gram-negative bacillary meningitis and bacteremia occurred in a patient who was receiving intrathecal and intravenous amphotericin B. An epidemiologic investigation found the amphotericin B to be contaminated with Enterobacter agglomerans, Pseudomonas fluorescens, and P aeruginosa. These contaminants were traced to a lot ot sodium phosphate buffer that was added to all intrathecal and intravenous amphotericin B preparations. The phosphate buffer underwent prolonged storage at room temperature and was not subject to terminal sterilization nor sterility testing. This parenteral admixture prepared in the hospital is now steam autoclaved and sterility tested before use.

Topics: Adult; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Drug Contamination; Enterobacter; Female; Humans; Hydrocephalus; Injections, Intravenous; Injections, Spinal; Meningitis; Pseudomonas aeruginosa; Pseudomonas fluorescens; Sepsis

Topics: Adult; Amphotericin B; Bone Marrow Diseases; Cryptococcosis; Cytosine; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Male; Meningitis

Cure of cryptococcal meningitis accompanied by cryptococcemia was achieved with amphotericin B therapy. Cryptococcal meningitis is associated with substantial morbidity and mortality, especially when accompanied by evidence of extraneural infection. Experience with the patient reported suggests that associated cryptococcemia is not invariably associated with treatment failure.

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis; Prognosis; Sepsis

Two patients with cryptococcal infection of the central nervous system are described. The first presented with signs of an intracranial mass and was subsequently shown to have two lesions within the brain which were later identified as cryptococcal granulomata. Antifungal therapy did not eradicate the lesions; following their excision and continued therapy, the CSF became sterile however. The other patient had signs of a fulminant meningoencephalitis which initially were thought to represent the pathophysiological expression of an expanding brain tumor. These reports are used as a basis to review the various aspects of central nervous system cryptococcosis, particularly as they may relate to the neurosurgeon and the therapy of the disease.

Topics: Aged; Amphotericin B; Brain Diseases; Cryptococcosis; Humans; Male

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Male

A patient with cryptococcal meningitis retractory to amphotericin B was treated primarily with intraventricular miconazole. All parameters of disease improved, and the patient was dischared after four months of therapy. In selected persons with cryptococcosis, it may be possible to successfully utilize intraventricular miconazole in the absence of concurrent intravenous medication.

Topics: Amphotericin B; Cryptococcosis; Humans; Imidazoles; Injections, Intraventricular; Male; Meningitis; Miconazole; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Lung Diseases, Fungal; Male

A patient in whom cryptococcal meningitis complicated a nine year old depressed frontal skull fracture, an association which has not been reported previously, is recorded. This is also the first case of cryptococcal meningitis recognised in Ethiopia.

Topics: Adult; Amphotericin B; Cryptococcosis; Ethiopia; Humans; Male; Meningitis; Skull Fractures

Cardiac toxic reactions and pulmonary consolidation in the left lower lobe developed in a patient who was receiving amphotericin B therapy for cryptococcal meningitis. Following surgical resection of the lobe, multiple subcutaneous cryptococcal abscesses appeared. Flucytosine administered intravenously failed to eradicate the lesions. Transfer factor therapy and multiple drainage procedures elimniated the skin abscesses. Transfer factor therapy was administered for one year; the patient was asymptomatic 16 months after therapy was discontinued.

Topics: Abscess; Aged; Amphotericin B; Cryptococcosis; Flucytosine; Heart; Humans; Lung Abscess; Male; Remission, Spontaneous; Skin Diseases, Infectious; Transfer Factor

A 61-year-old man with Trichosporon cutaneum (T. cutaneum) prosthetic valve endocarditis is reported. He had had an aortic valve replacement for rheumatic heart disease 3 years earlier. Onset of the valve infection was subacute. A systolic murmur was noted on admission. Subsequently, he developed conjunctival hemorrhages, hematuria and transient episodes of confusion, aphasia and cranial nerve palsies. Three of 17 blood cultures taken over 3 weeks were positive for T. cutaneum. He was given amphotericin B (AmB) and 5-fluorocytosine (5FC); T. cutaneum infection of prosthetic aortic valve was identified. The aortic valve was replaced. Postoperatively he developed refractory ventricular fibrillation and died. Striking synergy to AmB-5FC and AmB-rifampin combinations was demonstrated in vitro.

Topics: Amphotericin B; Aortic Valve; Cryptococcosis; Cryptococcus; Endocarditis, Subacute Bacterial; Flucytosine; Heart Valve Prosthesis; Humans; Male; Middle Aged

The clinical and pathological findings in 46 patients with cryptococcosis at Memorial Sloan-Kettering Cancer Center from 1956 to 1972 are reported. The striking predilection for cryptococcal infection in patients with leukemias and lymphomas is again confirmed. Of 41 patients with neoplastic disease, those with chronic lymphatic leukemia (CLL), Hodgkin's Disease, chronic myelogenous leukemia (CML), myeloma and lymphosarcoma had the highest incidence of cryptococcosis. In all cases, neoplastic disease was widespread when infection occurred. All of these patients had leukopenia and absolute lymphopenia at the time of infection. Thirty-nine were on steroids. Thirty-one patients with neoplastic disease had disseminated infection. Review of pathology revealed a spectrum of inflammatory lesions. Histiocytic-lymphocytic infiltrates occurred in the central nervous system in 10 patients. In six cases, reaction was granulomatous. There were single instances of suppurative and fibrotic reactions. Mortality from infection was high in patients with neoplastic disease. Twenty-four of 28 deaths occurred within 60 days as a result of infection. Within one year, 10 more patients died, nine of cryptococcosis. Only three survived more than one year, and all patients died within 600 days. Twenty-nine patients with neoplastic disease received amphotericin B. Only nine survived more than 60 days.

Topics: Amphotericin B; Antigens, Bacterial; Central Nervous System; Cryptococcosis; Cryptococcus neoformans; Female; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lung; Lymphoma, Large B-Cell, Diffuse; Male; Multiple Myeloma; Neoplasms

Trichothecin (T-cin), amphotericin B (AB), and 5-fluorocytosine (FC) were compared singly and in combination for capacities to inhibit growth of Cryptococcus neoformans in culture and to protect mice bearing infections with this yeast. The minimum inhibitory concentrations for T-cin, AB, and FC were found to be 0.5, 0.2, and 5.0 mug/ml, respectively. In vitro viability studies demonstrated a marked reduction in colony counts with the AB-FC combination and additive effects with the AB-T-cin and FC-T-cin combinations for a 3-day period. In mice infected intravenously with C. neoformans, the mean effective dose for AB was 0.38 mg/kg, and for FC it was 100 mg/kg for a 30-day treatment period. No mean effective dose could be ascertained when T-cin was tested at doses of 0.1 to 50 mg/kg. Despite this, marked beneficial effects were noted in vivo with the AB-T-cin combination, whereas additive effects and indifference were observed for AB-FC and FC-T-cin combinations, respectively. High-dose T-cin controls survived despite having received a cumulative dosage of more than twice the reported (LD(50)) mean lethal dose value.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Cytosine; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Female; Flucytosine; Male; Mice; Sesquiterpenes; Trichothecenes

An adult renal transplant recipient was complicated with cryptococcal lung granuloma and meningitis. Treatment with the antifungal agents, 5-fluorocytocin and clotrimazole had to be discontinued due to side effects. Whereas, the intrathecal administration of amphotericin B proved effective for meningitis but intravenously it induced acute tubular necrosis to the transplanted kidney. In order to cure the persistant fungal lung granulomas in renal transplant patients early surgical excision seems to be essential.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Cryptococcosis; Granuloma; Humans; Immunosuppressive Agents; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Lung Diseases, Fungal; Male; Meningitis; Postoperative Complications; Transplantation, Homologous

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Flucytosine; Humans; Kidney Transplantation; Male; Meningitis; Postoperative Complications; Transplantation, Homologous

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Drug Synergism; Drug Therapy, Combination; Flucytosine; Mice; Yeasts

Human cryptococcosis is an exogenous human infection of increasing frequency and growing importance. Early diagnosis is essential for the clinical outcome, no matter whether the infection is primary or secondary to underlying disease. Reliable and quick diagnostic methods are outlined and some pitfalls are discussed. Direct microscopy is essential, followed by cultivation procedures and serologic tests.

Topics: Agglutination Tests; Amphotericin B; Antibodies, Fungal; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Ecology; Flucytosine; Humans

The main emphasis in this paper is on the broad-spectrum antifungal agent amphotericin B and the narrow-spectrum agent flucytosine. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. 2-Hydrostilbamidine is used only in indolent cases of blastomycosis; this condition is usually treated with amphotericin B. A number of newer agents and combinations of drugs also warrant mention, but clinical experience is limited and these agents or combinations have not been approved for clinical use. Not all patients from whom fungal agents are isolated require treatment and the extent of the fungal infection should be determined when possible for evaluation of the need for treatment.

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Cytosine; Flucytosine; Humans; Stilbamidines

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Male; Meningitis

Two fatal cases of cryptococcal meningitis complicating adrenocorticosteroid-treated systemic lupus erythermatosus are reported. In one patient who was treated with flucytosine alone, after an initial period of improvement cryptococci resistant to flucytosine were isolated, and subsequent amphotericine B treatment silated, and subsequent amphotericin B treatment did not alter the progress of the disease. In the second patient, who received both drugs concurrently, resistant cryptococci did not appear and the patient recovered sufficiently to return home. Flucytosine-resistant mutants could be demonstrated in vitro in the original cryptococcal isolated from both patients. The use of flucytosine and amphotericin B in combination is discussed.

Topics: Amphotericin B; Cryptococcosis; Cytosine; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Flucytosine; Humans; Lupus Erythematosus, Systemic; Meningitis; Middle Aged

Topics: Amphotericin B; Child; Cryptococcosis; Female; Humans; Meningitis

Topics: Adult; Amphotericin B; Child; Cryptococcosis; Female; Flucytosine; Humans; Lung Diseases, Fungal; Male; Meningitis; Middle Aged

Topics: Adolescent; Amphotericin B; Brain Diseases; Cryptococcosis; Female; Granuloma; Humans; Male

Topics: Amphotericin B; Cryptococcosis; Humans; Male; Middle Aged; Pneumonia

A survey is given of the clinical picture of an infection with Cryptococcus neoformans. The symptoms and therapy are reviewed and the case history of a 13 year old boy suffering from this fungus infection is discussed.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Eye Diseases; Flucytosine; Humans; Male

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Immunosuppression Therapy; Kidney Transplantation; Meningitis; Postoperative Complications; Recurrence; Time Factors; Transplantation, Homologous

Ten cases of cryptococcosis have been identified in a 13 year experience with more than 650 renal transplants. Eight patients had meningitis, one patient had a cerebral granuloma, and in one patient the infection appeared to be limited to the lungs. The central nervous system infection often masqueraded as brain tumor and was not suspected initially. The most useful diagnostic test was cerebrospinal fluid examination including India ink preparation. Various ther apeutic regimens with amphotericin B and 5-fluorocytosine were effective in suppressing the infection. A combination of low doses of amphotericin B, not affecting kidney function, with 5-fluorocytosine for at least 3 months was associated with remission of disease in five patients who still are alive, including three patients without recurrence for longer than one year. Five deaths 3 weeks to 4 years after the beginning of treatment were not due to cryptococcosis; death resulted from vascular disease and septiciemia in three of the four patients with known causes of death. Central nervous system cryptococcosis, with the exception of the rare cerebral granuloma, is associated with little inflammation. If early death from increased intracranial pressure or cerebral edema is prevented, prolonged therapy with amphotericin B and 5-fluorocytosine may be expected to control the infection, even in immunosuppressed patients.

Topics: Adult; Amphotericin B; Brain Diseases; Child; Cryptococcosis; Drug Administration Schedule; Female; Flucytosine; Humans; Immunosuppression Therapy; Kidney Transplantation; Lung Diseases, Fungal; Meningitis; Middle Aged; Postoperative Complications; Pseudotumor Cerebri; Transplantation, Homologous

A simple method for the measurement of 5-fluorocytosine in the presence of amphotericin B is described. The antifungal activity of amphotericin B is abolished by heating serum at 100 C for 45 min. 5-Fluorocytosine is unaffected by this treatment, and serum levels can be subsequently assayed by either tube dilution or disk diffusion methods.

Topics: Amphotericin B; Biological Assay; Candida albicans; Candidiasis; Cryptococcosis; Cytosine; Flucytosine; Hot Temperature; Humans; Meningitis; Saccharomyces cerevisiae

Amphotericin B methyl ester (AME) has been reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME has been porposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the two polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis. Treatment consisted of two or more doses of each drug given by the intravenous route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. These studies have shown that AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections and that amphotericin B had a higher therapeutic ratio for all infections studied than did AME.

Topics: Amphotericin B; Animals; Ascorbic Acid; Blastomyces; Blastomycosis; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Dose-Response Relationship, Drug; Drug Evaluation; Lethal Dose 50; Male; Mice

Torulosis is an uncommon, but potentially lethal disease. The aim of this report is to indicate that resection of isolated pulmonary lesions due to torulosis is a safe procedure. Resection has proved useful in the definitive diagnosis and treatment of eight cases seen in this thoracic surgical unit.

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Lung Diseases, Fungal; Male; Meningitis; Middle Aged

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Male; Meningitis

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Flucytosine; Humans; Knee Joint; Radiography; Synovial Membrane; Synovitis

A 79-year-old female patient suffered from iridocyclitis of both eyes. In the fundus of the left eye equatorially a preretinal questionable granuloma (size 1/2 d.d.) was found; the first hint of a mycotic involvement. In the enucleated right bulbus, an abscess-like granulomatous focus with a diameter of 10 mm was found. Several round encapsulated cells having a diameter of 7 to 20 mu and looking like with Cryptococcus neoformans were microscopically demonstrable in the pus obtained from this abscess. Since the fungus could not be cultured, it may be assumed that a spontaneous healing occurred. The only known basic disease was a temporary uremia (330 mg0/0 urea and 7.0 mg0/0 creatinin). The role of amphotericin B therapy in this patient is discussed.

Topics: Aged; Amphotericin B; Cryptococcosis; Cryptococcus; Eye Diseases; Female; Humans

A case is described of cryptococcosis presenting as a large round intrathoracic lesion with superior vena caval obstruction and clubbing of the fingers. The patient was satisfactorily treated by lobectomy under cover of amphotericin B therapy.

Topics: Amphotericin B; Cryptococcosis; Humans; Lung Diseases, Fungal; Male; Middle Aged; Osteoarthropathy, Secondary Hypertrophic; Pneumonectomy; Vena Cava, Superior

Topics: Amphotericin B; Ampicillin; Brain Abscess; Candidiasis; Cryptococcosis; Enterobacteriaceae Infections; Esophagitis; Herpes Simplex; Humans; Infections; Meningitis; Meningitis, Listeria; Mucormycosis; Neoplasms; Pharyngitis; Stomatitis; Toxoplasmosis

Topics: Amphotericin B; Candida; Candidiasis; Cryptococcosis; Humans

A patient with chronic lymphocytic leukemia developed extensive pneumonia due to Cryptococcus neoformans. A presumptive diagnosis based on results of a Wright's stain of the sputum was made and appropriate antifungal therapy was started. C neoformans was cultured in COUNTS AS HIGH AS 8 X 10(5)/ml of sputum and was present morphologically for three weeks after sputum cultures had become negative. During the patient's first week of hospitalization, C neoformans was cultured from sputum and on cough plates but from no other source in his room. This suggests the possibility of transmitting the fungus to susceptible persons by droplets from patients having extensive pulmonary cryptococcosis.

Topics: Amphotericin B; Cryptococcosis; Humans; Leukemia, Lymphoid; Lung Diseases, Fungal; Male; Middle Aged; Sputum

Topics: Amphotericin B; Animals; Cat Diseases; Cats; Cryptococcosis; Female

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Headache; Humans; Meningitis; Papilledema

The in vitro and in vivo activities of amphotericin B and 5-fluorocytosine (5-FC) alone and in combination were studied to determine possible drug interactions against two strains of Cryptococcus neoformans, one sensitive to 5-FC and one resistant to 5-FC. In vitro tube dilution studies demonstrated only additive effects with the 5-FC-sensitive organism but antagonism with eth 5-FC-resistant organism. A mouse model of cryptococcal meningitis allowed comparative drug trails in a new model for the detection of drug interactions. Drug combinations were no more effective against meningitis caused by the 5-FC-sensitive organism than the additive effects of the individual drugs. However, meningitis caused by the 5-FC-resistant Cryptococcus responded less to drug combinations than to either drug alone. Serum levels of amphotericin B and 5-FC were comparable in all groups. No evidence of toxicity from the drug combinations was found. No inhibition of development of resistance to 5-FC by the combination with amphotericin B was detected.

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Cytosine; Disease Models, Animal; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Flucytosine; Meningitis; Mice

Immunologic studies were performed in two patients with sarcoidosis, who developed cryptococcosis. Polymorphonuclear leukocyte function, complement, and serum antibodies were normal. Both patients had depressed cell-mediated immunity (cmi) to Cryptococcus neoformans and other antigens that persisted after therapy for their infection. These findings suggest that the patients' impaired CMI predisposed them to cryptococcal infection, which complicated their sarcoidosis. Evaluation of sarcoidosis cases should include studies of immune function, and the possibility of a secondary infection should be considered in patients with long-standing sarcoidosis, who develop unexpected changes in their clinical status.

Topics: Amphotericin B; Candida; Cell Count; Cryptococcosis; Cryptococcus neoformans; Dinitrochlorobenzene; Female; Fibula; Flucytosine; Humans; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; In Vitro Techniques; Middle Aged; Radiography; Sarcoidosis; Skull; T-Lymphocytes

Renal transplant recipients are susceptible to a number of fungal infections amenable to therapy with amphotericin B, but azotaemia is an almost invariable sequel to the use of this agent. As intravenous mannitol has been shown to minimize nephrotoxicity induced by amphotericin B in dogs we treated four kidney transplant recipients who had systemic fungal infections with mannitol and amphotericin B. None showed significant reduction in renal function though a mild metabolic acidosis did develop.

Topics: Acidosis; Adult; Amphotericin B; Candidiasis; Cryptococcosis; Histoplasmosis; Humans; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Male; Mannitol; Middle Aged; Postoperative Complications; Transplantation, Homologous; Uremia

Disseminated cryptococcal infection is described in eight patients, seven of them with verified meningeal involvement. Six of the eight patients were recipients of a renal homograft and submitted to the classical immunosuppressive treatment. Consideration is given to predisposing factors and to problems in the clinical, biological and mycological diagnosis. Some comments are presented on the often disappointing results of antifungal therapy of cryptococcal meningitis.

Topics: Adult; Amphotericin B; Brain Diseases; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoma, Non-Hodgkin; Male; Meningitis; Middle Aged; Postoperative Complications; Sarcoidosis; Transplantation, Homologous

Since cryptococcosis is characterized by cryptococcoma formation, the antimycotic effect of amphothericin B was examined in view of such pathological-anatomical conditions. In white mice (NMRI), cryptococcoma formation was induced by intramuscular injection of Cryptococcus neoformans strain W71 into the hind leg (STAIB, 1962), using a suspension (0.2 ml) containing approximately 2.8 times 10-7 cells/ml. The mice were treated daily with 1 mg amphotericin B in 5% dimethyl sulfoxide by gastric intubation. Course of infection and effectivity of therapy were assessed by microbiological and patho-histological examination of the organs. In the present paper (2nd Communication) comparative patho-histological results in mice, treated with amphotericin B either immediately or from the 16th day p.i. or not at all, are reported. In the non-treated animals the course of infection we controlled by sacrificing 2 animals per day from the 2nd to the 25th day. Cryptococcoma found in the muscle, fat, and connective tissue in the hind leg of these animals were characterized by the two different patho-histological alterations: a) Masses of encapsulated cryptococci side by side were filling a paucireactive or non-reactive reticular structure with blood capillaries. b) Non-specific granulomatous tissue. The fungi were less abundantly found as non-encapsulated cells. On the 5th day after infection the first alterations due to dissemination were found in the lungs, then in other parenchymatous organs. Under immediate amphotericin B-therapy, no cryptococcoma was found at the place of infection; after a therapy of 30 days duration, C. neoformans could be detected in small conglomerates of non-encapsulated cells in muscle, fat and connective tissue. Histologically, a septic dissemination of the agent could not be found in this group. After a therapy of 25 days duration a shrinking of cryptococcoma was observed in animals treated from the 15th day after infection. Presumably this was caused by a loss of capsule and formation of non-specific granulomatous tissue. In the surroundings of blood vessels non-encapsulated cells were detectable. After therapy with amphotericin B, single cryptococci e.g. such disseminated into the lungs were increasingly showing morphological alterations which might be explained as forms of degeneration. The animal experiment in connection with microbiological and patho-histological follow-up studies is discussed with a view to the therapy of cryptococcosis i

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus neoformans; Injections, Intramuscular; Mice; Sepsis; Time Factors

Topics: Amphotericin B; Animals; Blastomyces; Clotrimazole; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Flucytosine; Imidazoles; Male; Mice; Sporothrix; Sporotrichosis

In three previously reported cases of cryptococcal meningitis, the only laboratory evidence for this diagnosis was the presence of cryptococcal antigen in the cerebrospinal fluid (CSF). Three additional patients had chronic meningitis and repeatedly negative CSF cultures and had cryptococcal antigen demonstrated in the CSF. In our patients, the diagnosis was further supported by the complete recovery after amphotericin B therapy in two and the demonstration of Cryptococcus neoformans in the meninges at autopsy in the third. In certain patients with chronic meningitis, the detection of cryptococcal antigen in the CSF may be the only means of establishing a diagnosis during life. In such patients, if cryptococcal antigen is present in the CSF in a titer of larger than or equal to 1:8, antifungal therapy should be initiated, pending results of other diagnostic studies.

Topics: Adult; Amphotericin B; Antigens, Fungal; Autopsy; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Male; Meningitis; Middle Aged

Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

Topics: Adolescent; Adult; Amphotericin B; Antibodies, Fungal; Aspergillosis; Bacterial Infections; Candidiasis; Cryptococcosis; Female; Flucytosine; Fungi; Histocompatibility Testing; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Middle Aged; Mycoses; Nocardia Infections; Phialophora; Postoperative Complications; Retrospective Studies

Topics: Actinomycosis; Amphotericin B; Blastomycosis; Candida albicans; Candidiasis, Cutaneous; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Griseofulvin; Histoplasmosis; Mucormycosis; Mycetoma; Sporotrichosis; Tinea Capitis; Tinea Pedis; Tinea Versicolor

Topics: Amphotericin B; Animals; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Cytosine; Drug Synergism; Flucytosine; Humans; Mice

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation; Humans; Male; Meningitis

An extradural toruloma developed in the lumbo-sacral region of a man. Symptoms had been present for two years, but he had been diagnosed as having tuberculosis of the lung seven years before. The mass was excised and the patient treated with Amphotericin B which had to be discontinued and Sulfa Soxizole substituted. He recovered and has remained symptom free for three years.

Topics: Amphotericin B; Cryptococcosis; Humans; Lumbosacral Region; Male; Middle Aged; Spinal Diseases; Sulfisoxazole

The comparative efficacy of amphotericin B and amphotericin B methyl ester (AME) against experimental histoplasmosis, blastomycosis, cryptococcosis, and candidosis in mice was assessed by determining the effect of daily intraperitoneal therapy on 21-day survival and persistence of organisms in internal organs. AME, like amphotericin B, was effective against each of the experimental infections, but the efficacy was lower than the parent compound. For Histoplasma and Blastomyces infections the mean effective dose (ED(50)) of amphotericin B was 0.3 mg/kg, whereas the corresponding values for AME, respectively, were 2.4 and 2.8 mg/kg. For Cryptococcus infection the ED(50) for amphotericin B was 0.2 mg/kg compared with 2.0 mg/kg for AME. The ED(50) of amphotericin B for Candida infection was lower than 0.05 mg/kg and the value of AME was between 0.5 to 0.05 mg/kg. The colony counts from internal organs of the surviving animals after the therapeutic regimens were compatible with the data on survival.

Topics: Amphotericin B; Animals; Blastomycosis; Candidiasis; Cryptococcosis; Esters; Histoplasmosis; Male; Mice

Immunosuppression, whether arising as a consequence of disease (haematopoietic and lymphoreticular malignancies) or therapy (against hemograft rejection or malignancy results in a higher than normal incidence of invasive fungal infections such as candidiasis, aspergillosis, mucormycosis and cryptococcosis. Normal host defense mechanisms, both immunologic and non-immunologic, are not fully functional and may contribute to the pathogenesis of these diseases.Candida, normally a superficial colonizer, may invade the gastrointestinal, respiratory or urinary tracts. Aspergillus and mucor species may cause hemorrhagic or necrotising pneumonias and secondarily spread to the brain. Cryptococcus may infect the meninges in the appropriate host. Therapeutics for these diseases is limited. Amphotericin B may alter the course of any of the four diseases. Fluorocystosine has found some use in the treatment of candidiasis and cryptococcosis.

Topics: Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Candidiasis; Clotrimazole; Cryptococcosis; Flucytosine; Humans; Immunity, Cellular; Immunosuppression Therapy; Immunosuppressive Agents; Leukocytes; Mucormycosis; Mycoses

Topics: Administration, Oral; Adult; Amphotericin B; Cryptococcosis; Cytosine; Flucytosine; Humans; Male; Meningitis

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans

Topics: Adult; Aged; Amphotericin B; Candida; Cryptococcosis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Humans; Lung Diseases, Fungal; Male; Mycoses

Mycoses for most of them) represent a group of infectious diseases which seem to increase steadily although numerous fungicidal or fungistatic therapeutics are available. A severe problem is provided by the so-called opportunistic fungi which become parasitic only after the host's immunological protection has been impaired by predisposing factors. Therapy resistance and prevention of relapse are problems of a general nature in the therapy of mycoses. As special topics local treatment of dermatophytoses, of Candida mycoses, and new development in systemic treatment of deep mycoses are discussed.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Clotrimazole; Cryptococcosis; Dermatomycoses; Drug Resistance, Microbial; Flucytosine; Fungi; Griseofulvin; Humans; Miconazole; Mycoses

In a prospective study from May 1971 to November 1973, 20 consecutive patients with a diagnosis of disseminated cryptococcosis were treated for six weeks with a combination of amphotericin B (20 mg daily) intravenously and flucytosine (150 mg/kg daily) orally. Fifteen patients has culturally docummented Cryptococcus neoformans meningitis, and three died of infection early in therapy. Of the remaining 12 patients, eight were alive and well eight to 34 months after therapy, and four died of other causes. None of the surviving patients has relapsed. Hematologic complications developed in nine patients, three of whom had no underlying lymphoreticular disorder or therapy with known cytotoxic agents. Renal insufficiency of mild degree occurred in only six patients. A shorter period of hospitalization and reduction in toxicity of amphotericin B suggest that combined therapy is a safe and efficacious alternative to other regimens.

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Hematologic Diseases; Humans; Kidney; Male; Meningitis; Middle Aged; Prospective Studies

Topics: Adult; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Male; Meningitis; Prednisone

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Drug Evaluation; Drug Therapy, Combination; Encephalitis; Flucytosine; Humans; Injections, Intravenous; Injections, Spinal; Male

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Aspergillosis; Biopsy; Blastomycosis; Candidiasis; Coccidioidomycosis; Complement Fixation Tests; Cryptococcosis; Fluorescent Antibody Technique; Fungi; Histoplasmin; Histoplasmosis; Humans; Immunity, Maternally-Acquired; Immunodiffusion; Immunosuppression Therapy; Lung; Methods; Mycoses; Precipitin Tests; Silver; Skin Tests; Sporotrichosis; Staining and Labeling; Stilbamidines

Topics: Administration, Oral; Amphotericin B; Animals; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Intubation, Gastrointestinal; Male; Mice

Topics: Amphotericin B; Animals; Arachnoiditis; Cervical Vertebrae; Cisterna Magna; Coccidioidomycosis; Cryptococcosis; Glucose; Haplorhini; Injections, Spinal; Lumbar Vertebrae; Macaca; Meningitis; Methods; Models, Biological; Posture; Serum Albumin, Radio-Iodinated; Solutions; Specific Gravity; Thoracic Vertebrae; Water

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Humans; Male; Meningitis; Polyradiculopathy

Topics: Amphotericin B; Cryptococcosis; Humans; Male; Meningoencephalitis; Middle Aged

Topics: Amphotericin B; Antibodies; Complement System Proteins; Cryptococcosis; Flucytosine; Humans; Immunity, Cellular; Immunoelectrophoresis; Lung Diseases; Male; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Meningitis; Middle Aged

Topics: Amphotericin B; Autopsy; Cryptococcosis; Cryptococcus; Cytosine; Drug Resistance, Microbial; Humans; Meningoencephalitis

Topics: Adult; Amphotericin B; Brain Diseases; Cryptococcosis; Humans; Injections, Intravenous; Injections, Spinal; Lung; Lung Diseases; Male; Pneumonectomy

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Male; Middle Aged; Taiwan

Topics: Amphotericin B; Animals; Cryptococcosis; Cytosine; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Flucytosine; Humans; Male; Meningitis; Pregnancy; Pregnancy Complications, Infectious; Rats

Topics: Amphotericin B; Antibodies, Fungal; Biopsy; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Male; Middle Aged; Nasal Mucosa; Nose Diseases

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Cytosine; Drug Resistance, Microbial; Female; Flucytosine; Humans; Injections, Intravenous; Injections, Spinal; Male; Meningitis; Middle Aged

Topics: Adult; Aged; Amphotericin B; Anterior Chamber; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Cytosine; Drug Resistance, Microbial; Female; Flucytosine; Humans; Keratitis; Kidney Diseases; Kidney Transplantation; Male; Meningitis; Middle Aged; Mycoses; Transplantation, Homologous

Topics: Amphotericin B; Antigens, Fungal; Blood; Cryptococcosis; Cryptococcus; Follow-Up Studies; Humans; Leukocyte Count; Maryland; Meningitis; Prognosis

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Meningitis

Topics: Administration, Oral; Adolescent; Adult; Amphotericin B; Child; Cryptococcosis; Cytosine; Female; Humans; Injections, Intravenous; Kidney; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Biopsy; Cholangitis; Cryptococcosis; Diagnostic Errors; Flucytosine; Granuloma; Hepatitis; Humans; Liver; Male; Meningitis; Neurologic Manifestations

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Meningitis; Mycoses; Natamycin; Nocardia Infections; Penicillin G; Potassium Iodide; Sporotrichosis; Stilbamidines; Sulfonamides

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: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Cytosine; Humans; Lung Diseases, Fungal; Meningitis

Topics: Amphotericin B; Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Cytosine; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Synergism; Flucytosine; Injections, Intraperitoneal; Injections, Intravenous; Mice; Microbial Sensitivity Tests

Topics: Adolescent; Amphotericin B; Antigens, Fungal; Ascitic Fluid; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Peritonitis; Prednisone

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Middle Aged; Ointments; Skin Ulcer

Topics: Adolescent; Adult; Amphotericin B; Australia; Child; Climate; Cryptococcosis; Cryptococcus neoformans; Ethnicity; Female; Humans; Lung Diseases, Fungal; Male; Meningitis; Middle Aged; Occupations; Sex Factors

Topics: Amphotericin B; Antibodies; Antilymphocyte Serum; Azathioprine; Buttocks; Cadaver; Cryptococcosis; Cryptococcus neoformans; Humans; Injections, Intramuscular; Kidney Transplantation; Lymphoma, Non-Hodgkin; Male; Meningitis; Middle Aged; Postoperative Care; Prednisone; Spleen; Transplantation, Homologous

Topics: Adrenal Gland Diseases; Adrenal Glands; Adult; Amphotericin B; Autopsy; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Prednisone

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Lung Diseases, Fungal; Male; Meningitis; Middle Aged; Pneumonectomy; Postoperative Complications; Sputum

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Diethylstilbestrol; Drug Resistance, Microbial; Estradiol; Estrogens; Humans; Meningitis; Norethynodrel; Pregnanes; Progesterone; Testosterone; Time Factors

Topics: Amphotericin B; Animals; Columbidae; Cryptococcosis; Cryptococcus neoformans; Feces; Humans; Lung Diseases, Fungal; Serologic Tests

Topics: Adenine; Aminoglycosides; Amphotericin B; Animals; Antifungal Agents; Blastomyces; Blastomycosis; Candida; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus; Culture Media; Drug Synergism; Histoplasma; Mice; Microsporum; Sporothrix; Trichophyton

Topics: Amphotericin B; Coccidioidomycosis; Cryptococcosis; Female; Fetus; Humans; Pregnancy; Pregnancy Complications, Infectious

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Meningitis

Topics: Age Factors; Amphotericin B; Child; Cryptococcosis; Facial Paralysis; Humans; Male; Neurodermatitis

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Iodides; Mycoses; Nystatin; Sporotrichosis

Topics: Agranulocytosis; Amphotericin B; Antineoplastic Agents; Aspergillosis; Candidiasis; Cryptococcosis; Cytosine; Diabetes Complications; Glucocorticoids; Humans; Immunosuppression Therapy; Mucormycosis; Mycoses; Nystatin

Topics: Amphotericin B; Bacterial Infections; Catheterization; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Chronic Disease; Coccidioidomycosis; Cryptococcosis; Humans; Hydrocephalus; Injections, Spinal; Meningitis; Methods; Time Factors; Wound Infection

Five cases are described in which fear of the possibly hazardous effects of giving amphotericin to patients with kidney disease resulted in death from progressive infection by an amphotericin-sensitive fungus (Cryptococcus neoformans in three cases, Blastomyces dermatitidis in one case, and Histoplasma capsulatum in one case).

Topics: Adrenal Insufficiency; Adult; Amphotericin B; Attitude of Health Personnel; Blastomycosis; Cryptococcosis; Decerebrate State; Drug Prescriptions; Female; Histoplasmosis; Hodgkin Disease; Humans; Kidney Diseases; Lung Diseases, Fungal; Male; Medication Errors; Meningitis; Meningoencephalitis; Mycoses; Phobic Disorders; Sarcoidosis; Spinal Diseases

Topics: Adult; Aged; Amphotericin B; Brain Diseases; Cryptococcosis; Female; Follow-Up Studies; Humans; Indium; Injections, Spinal; Male; Middle Aged; Radionuclide Imaging; Serum Albumin, Radio-Iodinated; Subarachnoid Space; Technetium; Ytterbium

Topics: Adult; Amphotericin B; Brain Diseases; Cerebral Angiography; Cryptococcosis; Follow-Up Studies; Granuloma; Humans; Injections, Intravenous; Injections, Spinal; Male; Motor Cortex; Recurrence

Topics: Adult; Amphotericin B; Biopsy; Cryptococcosis; Female; Fluorescent Antibody Technique; Histiocytes; Humans; Inclusion Bodies; Latex Fixation Tests; Macrophages; Male; Middle Aged; Neutrophils; Organoids; Skin; Skin Diseases, Infectious

Topics: Amphotericin B; Cryptococcosis; Diagnosis, Differential; Humans; Lung Diseases, Fungal

Topics: Adult; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Female; Humans; Lung Diseases, Fungal; Meningitis; Natamycin; Tuberculosis, Meningeal

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antimetabolites; Aspergillosis; Aspergillus; Candida albicans; Candidiasis; Child; Cryptococcosis; Cytosine; Female; Fluorine; Humans; Infant; Male; Middle Aged; Mycoses; Phialophora; Sporothrix

Topics: Amphotericin B; Autopsy; Cryptococcosis; Cryptococcus neoformans; Cytosine; Fluorine; Hodgkin Disease; Humans; Male; Middle Aged; Pleura; Pleural Diseases; Pleural Effusion

Topics: Adolescent; Adult; Amphotericin B; Animals; Asian People; Cerebrospinal Fluid Proteins; Child; Columbidae; Cryptococcosis; Cryptococcus neoformans; Cytosine; Evaluation Studies as Topic; Female; Glucose; Humans; Hypertension; Lung Diseases; Male; Meningitis; Middle Aged; Myasthenia Gravis; Peptic Ulcer; Prognosis; Schizophrenia; Singapore; Tuberculosis, Meningeal

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Lung; Lung Diseases, Fungal; Male

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Humans; Meningitis; Pregnancy; Pregnancy Complications, Infectious

Topics: Adult; Aminosalicylic Acids; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Humans; Isoniazid; Lung Diseases, Fungal; Male; Mycobacterium tuberculosis; Radiography; Tuberculosis, Pulmonary

Topics: Aged; Amphotericin B; Cryptococcosis; Cryptococcus; Humans; Lung Diseases, Fungal; Male

Topics: Amphotericin B; Cryptococcosis; Female; Humans; Lupus Erythematosus, Systemic; Meningitis; Methylprednisolone; Middle Aged

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; Amphotericin B; Biopsy; Catheterization; Cryptococcosis; Humans; Lipids; Lung; Lung Diseases, Fungal; Male; Proteins; Pulmonary Alveolar Proteinosis; Radiography; Sex Factors; Therapeutic Irrigation; Vital Capacity

Topics: Adult; Amphotericin B; Azathioprine; Creatinine; Cryptococcosis; Cryptococcus; Cytosine; Female; Fluorine; Humans; Kidney Diseases; Kidney Transplantation; Male; Metabolic Clearance Rate; Postoperative Complications; Transplantation, Homologous

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Diagnosis, Differential; Face; Female; Humans; Japan; Lupus Erythematosus, Discoid

Topics: Aerosols; Aged; Amphotericin B; Bronchi; Cryptococcosis; Humans; Lung Diseases, Fungal; Male; Nystatin

Topics: Amphotericin B; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Middle Aged

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Male

Topics: Adult; Amphotericin B; Candidiasis, Cutaneous; Cryptococcosis; Female; Humans; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Kidney Diseases; Meningitis

Topics: Amphotericin B; Animals; Aspergillosis; Blastomycosis; Candidiasis; Cat Diseases; Cats; Coccidioidomycosis; Cryptococcosis; Dog Diseases; Dogs; Histoplasmosis; Mycoses; Sporotrichosis

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Drug Resistance, Microbial; Humans; Injections, Intravenous; Injections, Spinal; Microbial Sensitivity Tests; Thailand

Topics: Amphotericin B; Cryptococcosis; Diagnosis, Differential; Follow-Up Studies; Humans; Lung; Lung Diseases; Lung Diseases, Fungal; Postoperative Care; Radiography

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Blood Urea Nitrogen; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Cytosine; Drug Resistance, Microbial; Endocarditis; Fluorine; Heart Valve Prosthesis; Humans; Male; Meningitis; Middle Aged; Postoperative Complications

Topics: Aged; Agglutination Tests; Amphotericin B; Antigens; Antigens, Bacterial; Cryptococcosis; Cryptococcus; Humans; Latex; Male; Meningitis; Microspheres; Middle Aged

Topics: Agglutination Tests; Amphotericin B; Antigens; Blindness; Cataract; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Culture Media; Humans; Hypertonic Solutions; Male; Methods; Middle Aged; Retinal Detachment; Rubber; Sucrose; Triamcinolone; Uveitis

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Humans; Male; Middle Aged; Sputum; Staining and Labeling

Topics: Adrenal Glands; Agammaglobulinemia; Amphotericin B; Brain; Carcinoma; Carcinoma, Hepatocellular; Cryptococcosis; Cryptococcus; Diabetes Complications; Granuloma; Humans; Immunologic Deficiency Syndromes; Kidney Neoplasms; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

Topics: Aged; Amphotericin B; Biopsy; Cryptococcosis; Female; Fluorescent Antibody Technique; Humans; Serologic Tests; Skin Diseases, Infectious

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Chemical Phenomena; Chemistry; Chromoblastomycosis; Cryptococcosis; Cytosine; Fluorine; Fungi; Haplorhini; Humans; Injections, Subcutaneous; Mice; Rats

Topics: Amphotericin B; Cryptococcosis; Humans; Meningitis

Topics: Adult; Amphotericin B; Asian People; Body Temperature; Bone Diseases; Cryptococcosis; Granulation Tissue; Humans; Injections, Intravenous; Joint Diseases; Malaysia; Male; Pulse; Radiography; Sternum

Topics: Adolescent; Adult; Aged; Amphotericin B; Blood Cells; Carotid Arteries; Cerebral Ventriculography; Cerebrospinal Fluid; Cryptococcosis; Electroencephalography; Female; Hemoglobinometry; Humans; Hydrocephalus; Liver Function Tests; Lung; Male; Meningitis; Middle Aged; Neural Conduction; Neurologic Manifestations; Papilledema; Peripheral Nerves; Potassium; Pressure; Prognosis; Time Factors; Urea; Vision Disorders

Topics: Amphotericin B; Child; Child, Preschool; Cryptococcosis; Cytosine; Female; Fluorides; Humans; Male; Meningitis; Prognosis

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

Topics: Adult; Amphotericin B; Biopsy; Cryptococcosis; Humans; Lung Diseases, Fungal; Male; Meningitis; Meningococcal Infections; Radiography

Topics: Adult; Aged; Aminohippuric Acids; Amphotericin B; Biological Transport, Active; Blood Urea Nitrogen; Coccidioidomycosis; Cryptococcosis; Glomerular Filtration Rate; Histoplasmosis; Humans; Inulin; Kidney Concentrating Ability; Kidney Function Tests; Kidney Tubules; Male; Middle Aged; Mycoses; Natriuresis; Potassium; Urea

Topics: Adult; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Drainage; Female; Humans; Meningitis

Two patients on prolonged steroid therapy developed meningitis due to Cryptococcus neoformans. The first responded satisfactorily to treatment with amphotericin B, both initially and again following relapse. The second died shortly after treatment was begun. Pathogenicity studies suggest that the strain isolated from the fatal case was the more virulent. Cryptococcal meningitis probably occurs more often in Britain than is generally appreciated, and this possibility should be remembered when investigating patients with obscure forms of meningitis; if not, then the correct diagnosis may not be made. Attention is drawn to the increasing number of recently reported cases of this disease which have been associated with long-term steroid therapy.

Topics: Adult; Aged; Amphotericin B; Blood Cell Count; Carbohydrates; Cerebrospinal Fluid Proteins; Cryptococcosis; Female; Glucocorticoids; Humans; Male; Meningitis; Middle Aged; Nausea; Urea; Vomiting

The effect of X irradiation on the survival time of animals experimentally infected with pathogenic fungi was studied, and the activity of antifungal agents in pre-irradiated hosts was evaluated. A 24-hr preinfection dose of X irradiation decreased the survival time of mice infected with Cryptococcus neoformans and Histoplasma capsulatum to a greater extent than Candida albicans or Blastomyces dermatitidis infections. Exposure to 400 r caused a significant reduction in the variation (S(2)) survival time of C. albicans or H. capsulatum mouse infections. A single 100-mg/kg dose of 5-fluorocytosine or amphotericin B administered within 24 hr postinfection significantly extended the survival time of mice infected with C. albicans. Delayed treatment with amphotericin B was effective against C. neoformans infections. Four 50-mg/kg doses of 5-fluorocytosine were more effective than a single 200-mg/kg dose against C. neoformans infections. A single dose of amphotericin B provided significant protection when administered 48 hr postinfection against B. dermatitidis in preirradiated mice. A single dose of saramycetin 48 hr postinfection was highly effective against H. capsulatum mouse infections. A 100-mg/kg dose of amphotericin B was only effective against this fungal pathogen when administered within 8 hr postinfection. In vivo activity of the antifungal agents studied was detected within 8 to 14 days. The relative in vivo activity of several antifungal agents indicated the importance of considering their individual pharmacological properties for optimum effectiveness. The experimental model used in this study should be useful for the detection and for the preclinical evaluation of new antifungal agents.

Topics: Amphotericin B; Animals; Antifungal Agents; Blastomyces; Blastomycosis; Candida; Cryptococcosis; Cryptococcus; Cytosine

Topics: Adult; Amphotericin B; Back; Biopsy; Cerebral Ventricles; Cryptococcosis; Cryptococcus; Dermatomycoses; Diagnosis, Differential; Female; Humans; India; Lung; Lung Diseases, Fungal; Male; Meningitis; Middle Aged; Skin

Topics: Amphotericin B; Animals; Child; Cryptococcosis; Cryptococcus; Humans; Male; Mice

Topics: Amphotericin B; Animals; Cat Diseases; Cats; Cryptococcosis; Cryptococcus; Dura Mater; Male; Muscles; Penicillins; Streptomycin; Temporal Bone

(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: Adult; Amphotericin B; Cryptococcosis; Humans; Hypokalemia; Kidney; Kidney Concentrating Ability; Male; Meningitis; Muscular Diseases; Myoglobinuria; Potassium; Potassium Chloride

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Humans

Topics: Amphotericin B; Animals; Blood; Brain; Cryptococcosis; Cryptococcus; Drug Resistance, Microbial; Kidney; Liver; Lung; Mesentery; Mice; Peritoneum; Polymyxins; Spleen; Virulence

Topics: Adult; Amphotericin B; Azathioprine; Cryptococcosis; Female; Humans; Kidney Transplantation; Lung Diseases, Fungal; Melphalan; Polycystic Kidney Diseases; Prednisone; Transplantation, Homologous

Topics: Amphotericin B; Child; Cryptococcosis; Female; Humans; Leukemia, Lymphoid; Leukocyte Count; Meningitis

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Lung Diseases, Fungal; Male; Pleural Effusion; Radiography; Solitary Pulmonary Nodule

Topics: Adult; Amphotericin B; Brain; Cryptococcosis; Diagnosis, Differential; Heart Diseases; Humans; Lung; Male; Meningitis; Nephrocalcinosis; Prednisolone; Sarcoidosis; Sepsis

Topics: Actinomycosis; Amphotericin B; Antifungal Agents; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Mucormycosis; Mycoses; Nocardia Infections; Sporotrichosis

Topics: Adult; Aged; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Diabetes Complications; Female; Follow-Up Studies; Hodgkin Disease; Humans; Leukemia, Lymphoid; Lupus Erythematosus, Systemic; Male; Meningitis; Middle Aged; Sarcoidosis; Silicosis

Topics: Amphotericin B; Autopsy; Child; Chloramphenicol; Cryptococcosis; Hodgkin Disease; Humans; Hydrocortisone; Male; Salmonella Infections; Skin Manifestations; Spinal Diseases

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Pleural Effusion; Sarcoidosis; Skin Manifestations

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus; Humans; Male; Middle Aged; Tuberculosis, Pulmonary

Topics: Adult; Amphotericin B; Child; Cryptococcosis; Cytosine; Female; Humans; Meningitis

Topics: Adolescent; Adult; Amphotericin B; Child; Cryptococcosis; Female; Humans; Injections, Spinal; Radiography

Topics: Amphotericin B; Arachnoiditis; Biological Transport; Blood Glucose; Blood-Brain Barrier; Cryptococcosis; Glucose; Humans; Meningitis; Models, Biological

Topics: Amphotericin B; Bone Diseases; Brain Diseases; Cryptococcosis; Female; Humans; India; Middle Aged; Skin Diseases, Infectious; Skin Ulcer

Topics: Adult; Amphotericin B; Conjunctiva; Cryptococcosis; Cryptococcus; Eye Diseases; Fundus Oculi; Humans; Lupus Erythematosus, Systemic; Male; Meningitis; Necrosis; Optic Nerve; Papilledema; Prednisone; Pupil; Retina; Retinitis

Topics: Actinomycosis; Adult; Amphotericin B; Biopsy; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Diagnosis, Differential; Female; Histoplasmosis; Humans; Male; Middle Aged; Mycoses; Nystatin; Respiratory Tract Infections; Skin; Skin Diseases; Skin Ulcer; South America; Sputum

The antifungal activity of pyrrolnitrin, previously shown to be effective against superficial infections, was evaluated against experimental systemic mycoses. Pyrrolnitrin was inhibitory in vitro at <0.78 to 100 mug/ml to Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, Sporotrichum schenckii, and Histoplasma capsulatum. Pyrrolnitrin activity was reduced about 90% in sera. After multiple subcutaneous doses of pyrrolnitrin at 20 mg/kg, activity was recovered in mouse blood and urine as well as kidney, liver, and brain homogenates. Multiple daily doses (50 mg/kg) of this antibiotic were effective in reducing by 74% the number of viable cells of C. albicans recovered from kidney homogenates. Multiple doses (15 mg/kg) resulted in a 74% reduction in the number of C. neoformans from brain homogenates. Pyrrolnitrin was ineffective in reducing the recovery of B. dermatitidis or H. capsulatum from liver or spleen homogenates of infected mice. When compared with amphotericin B, hamycin, 5-fluorocytosine, and saramycetin, this antibiotic was less effective. This study indicates that pyrrolnitrin would have limited usefulness as a systemic antifungal agent.

Topics: Amphotericin B; Animals; Antifungal Agents; Blastomyces; Blastomycosis; Blood; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Histoplasma; Histoplasmosis; Mice; Neurospora; Sporothrix

Cryptococcal meningitis occurred in two patients in the North of England. One, an elderly woman who was ill for 12 months with an obscure indolent meningitis until use of steroid drugs resulted in an acute exacerbation during which cryptococci were isolated, was treated successfully with amphotericin B. The other, a student from New Guinea with subacute meningitis, could not tolerate amphotericin B but responded to two courses of oral treatment with 5-fluorocytosine 100-200 mg./kg./ day without any appreciable side-effects. Further trials of this drug in the treatment of cryptococcosis are recommended.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Cytosine; Female; Fluorides; Humans; Male; Meningitis; Middle Aged; Prednisone

Topics: Adult; Aged; Amphotericin B; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Male; Middle Aged; Mononuclear Phagocyte System; Mycoses; Phagocytosis; Serum Albumin, Radio-Iodinated

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus; Humans; Male; Meningitis

Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Betamethasone; Cryptococcosis; Female; Humans; Meningitis; Prednisolone

Topics: Adult; Amphotericin B; Atrophy; Craniotomy; Cryptococcosis; Humans; Male; Meningitis; Optic Chiasm; Optic Nerve; Vision Disorders

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Humans; Injections, Spinal; Meningitis; Models, Theoretical

MAXIMAL SEROLOGICAL DIAGNOSIS OF CRYPTOCOCCOSIS MAY BE ACCOMPLISHED THROUGH THE CONCURRENT USE OF THREE TESTS: the latex agglutination (LA) test for cryptococcal antigen, and the indirect fluorescent antibody (IFA) and tube agglutination (TA) tests for Cryptococcus neoformans antibodies. These tests were applied to 141 serum and cerebral spinal fluid specimens from 66 culturally proven cases of cryptococcosis and to 42 sera from normal subjects and from patients with other systemic mycotic diseases. The LA test was sensitive and completely specific; of the sera from proven cases, 55% were positive. With the TA test, 37% of the specimens were positive and the test was highly specific. With the IFA test, 38% of the specimens were positive and the test appears to be the least specific of the three. Cross-reactions were most evident with blastomycosis and histoplasmosis case sera. When the three tests were used concurrently, 87% of the cryptococcosis case specimens were positive and permitted a presumptive diagnosis of C. neoformans infections in 61 (92%) of the 66 patients whose specimens were examined.

Topics: Amphotericin B; Complement Fixation Tests; Cryptococcosis; Fluorescent Antibody Technique; Hemagglutination Tests; Humans; Latex Fixation Tests; Mycoses

Topics: Acute Disease; Adult; Amphotericin B; Arachnoiditis; Cryptococcosis; Humans; Laminectomy; Male; Myelography; Spinal Cord Diseases; Subarachnoid Space

Topics: Adult; Aged; Amphotericin B; British Columbia; Cryptococcosis; Female; Humans; Male; Meningitis

Topics: Amphotericin B; Cross Infection; Cryptococcosis; Cryptococcus; Humans; Pyelonephritis

Topics: Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Arthritis, Rheumatoid; Aspirin; Cryptococcosis; Cryptococcus; Female; Hematuria; Humans; Kidney Papillary Necrosis; Male; Meningitis; Middle Aged; Proteinuria; Pyelonephritis; Pyuria; Urea; Urinary Tract Infections

Topics: Adrenal Cortex Hormones; Aged; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus; Humans; Male; Meningoencephalitis; Middle Aged; Primary Myelofibrosis; Sarcoidosis

Topics: Amphotericin B; Brain; Brain Diseases; Cryptococcosis; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Amphotericin B; Blastomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Myocardial Infarction; Radiography

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Cryptococcosis; Histoplasmosis; Humans; Mice; Mucormycosis; Mycoses; Nocardia Infections; Prognosis; Sulfanilamides; Sulfonamides

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cryptococcus; Female; Humans; Male; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Urinary Tract Infections

Topics: Adult; Amphotericin B; Calcium; Calcium Isotopes; Calcium, Dietary; Carcinoma; Cellulose; Cryptococcosis; Feces; Humans; Hypercalcemia; Intestinal Absorption; Kinetics; Magnesium; Male; Middle Aged; Parathyroid Neoplasms; Phosphates; Phosphorus; Sarcoidosis

Topics: Amphotericin B; Bone Diseases; Cryptococcosis; Diagnosis, Differential; Female; Humans; Middle Aged; Osteolysis, Essential; Ribs; Sarcoidosis

Topics: Adult; Aged; Amphotericin B; Bronchi; Cryptococcosis; Cryptococcus; Female; Follow-Up Studies; Humans; Lung Diseases; Lung Diseases, Fungal; Male; Middle Aged; Pleural Effusion; Radiography; Sputum

Topics: Adult; Aged; Amphotericin B; Biopsy; Bronchi; Cryptococcosis; Cryptococcus; Female; Humans; Lung; Lung Diseases; Lung Diseases, Fungal; Lymphadenitis; Male; Middle Aged; Sputum

Topics: Alkenes; Amphotericin B; Animals; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Mice

Topics: Adolescent; Adult; Aged; Amphotericin B; Bone Marrow; Cerebrospinal Fluid Proteins; Cryptococcosis; Cryptococcus; Culture Techniques; Feces; Female; Glucose; Histoplasma; Histoplasmosis; Humans; Intracranial Pressure; Male; Meningitis; Middle Aged; Skin; Sputum

Topics: Adult; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Diagnosis, Differential; Europe; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningoencephalitis; Spinal Puncture

Topics: Amphotericin B; Cryptococcosis; Encephalitis; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Biopsy; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Lung Diseases, Fungal; Male; Middle Aged; Nocardia Infections; Radiography

Topics: Amphotericin B; Cryptococcosis; Granuloma; Humans; Male; Middle Aged; Skull Neoplasms

Topics: Amphotericin B; Cryptococcosis; Diabetes Complications; Endocarditis; Humans; Male; Middle Aged

Topics: Amphotericin B; Cisterna Magna; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Epidemiologic Methods; Female; Humans; Middle Aged; Skin Ulcer

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis

Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Humans; Male; Meningitis; Prognosis

Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Cryptococcosis; Humans; Lung Diseases, Fungal; Male; Meningitis

Topics: Actinomycosis; Adult; Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis, Vulvovaginal; Child; Cryptococcosis; Dermatomycoses; Female; Griseofulvin; Humans; Lung Diseases, Fungal; Mycetoma; Mycoses; Nails; Nocardia Infections; Nystatin; Skin Diseases; Sporotrichosis; Stilbamidines; Thallium; Tinea Pedis

Topics: Adult; Amphotericin B; Animals; Cryptococcosis; Female; Humans; Meningitis; Mice

Topics: Adult; Amphotericin B; Cerebrospinal Fluid; Coma; Cryptococcosis; Female; Headache; Humans; Injections, Intramuscular; Meningitis; Prednisolone; Spinal Puncture

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Diagnosis, Differential; Humans; Male; Nystatin

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus neoformans; Hodgkin Disease; Humans; Male; Pericarditis; Young Adult

Topics: Amphotericin B; Animals; Cryptococcosis; Dog Diseases; Dogs; Skin Manifestations

Topics: Aged; Amphotericin B; Cryptococcosis; Diabetes Complications; Female; Humans; Kidney Diseases

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Lung Diseases, Fungal

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Humans; Male; Middle Aged; Radiography, Thoracic

Topics: Adolescent; Adult; Aged; Amphotericin B; Cryptococcosis; Female; Humans; Male; Middle Aged; Prednisone; Sarcoidosis

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Leukemia, Lymphoid

Topics: Adrenal Cortex Hormones; Amphotericin B; Brain Diseases; Cryptococcosis; Cryptococcus; Diagnosis, Differential; Humans; Lung Diseases, Fungal; Male; Middle Aged; Radiography, Thoracic; Tuberculosis, Pulmonary

Topics: Amphotericin B; Cryptococcosis; Humans; Mycoses

Topics: Adrenal Cortex Hormones; Adult; Agglutination Tests; Amphotericin B; Antigen-Antibody Reactions; Cryptococcosis; Female; Humans; Male; Middle Aged; Prognosis; Serologic Tests

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Meningoencephalitis

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

Topics: Amphotericin B; Cryptococcosis; Drug Therapy; Fungi; Humans; Lung Diseases, Fungal; Pathology; Radiography, Thoracic

Topics: Amphotericin B; Antineoplastic Agents; Cryptococcosis; Drug Therapy; Hodgkin Disease; Humans; Male; Pathology; Prostatitis

Topics: Amphotericin B; Biomedical Research; Blastomycosis; Chlorpromazine; Coccidioidomycosis; Cryptococcosis; Drug Therapy; Fever; Histoplasmosis; Humans; Lactose; Nausea; Pentobarbital; Sporotrichosis; Toxicology; Vomiting

Topics: Amphotericin B; Biopsy; Cryptococcosis; Diagnosis, Differential; Drug Therapy; Humans; Lung Diseases; Lymph Nodes; Pathology; Prednisone; Sarcoidosis

A case of cryptococcal meningo-encephalitis is described. Treatment with the fungicidal agent amphotericin B resulted in temporary improvement, but the patient relapsed and died 17 months after diagnosis. The pathology and treatment of the disease are discussed.

Topics: Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Drug Therapy; Encephalitis; Humans; Meningoencephalitis; Pathology

Topics: Amphotericin B; Cryptococcosis; Drug Therapy; Pathology; Radiography; Spinal Diseases

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Drug Therapy; Humans; Meningitis

Topics: Amphotericin B; Cryptococcosis; Drug Therapy; Fistula; Geriatrics; Humans; Leukemia; Male; Pathology; Postoperative Complications; Prostate; Prostatectomy

Topics: Aged; Amphotericin B; Cryptococcosis; Drug Therapy; Fungi; Geriatrics; Humans; Lung Diseases; Lung Diseases, Fungal; Postoperative Care; Radiography, Thoracic; Surgical Procedures, Operative

Topics: Adult; Amphotericin B; Antibody Formation; Cryptococcosis; Humans; Meningitis; Myasthenia Gravis; Thymoma

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Lung Diseases, Fungal; Male; Middle Aged; Radiography, Thoracic; Tomography

Topics: Adolescent; Amphotericin B; Cryptococcosis; Hematuria; Humans; Male; Prostatic Diseases; Pyuria; Urination Disorders

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Female; Humans; Postoperative Complications; Sepsis; Thymectomy

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Female; Humans; Postoperative Complications; Sepsis; Thymectomy

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Male; Skin Diseases

Topics: Adult; Amphotericin B; Catheterization; Coccidioidomycosis; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Injections, Subcutaneous; Male; Meningitis; Middle Aged

Topics: Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Follow-Up Studies; Headache; Humans; Meningitis; Meningitis, Cryptococcal; Prognosis; Statistics as Topic; Toxicology

Topics: Amphotericin B; Cryptococcosis; Eye Manifestations; Humans; Meningitis; Meningitis, Cryptococcal; Ophthalmology; Optic Atrophy; Papilledema; Pathology

Topics: Adrenal Gland Diseases; Amphotericin B; Brain Diseases; Cerebrospinal Fluid; Cryptococcosis; Dermatomycoses; Diagnosis; Gastroenterology; Geriatrics; Histoplasmosis; Humans; Lung Diseases; Lung Diseases, Fungal; Meningitis; Pathology

Topics: Alkaline Phosphatase; Amphotericin B; Biopsy; Black People; Cryptococcosis; Hepatomegaly; Humans; Liver Diseases; Lymph Nodes; Mesenchymoma; Muscular Diseases; Neoplasms; Serologic Tests; Surgical Procedures, Operative; Thigh

Topics: Actinomycosis; Amphotericin B; Biomedical Research; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Cycloserine; Erythromycin; Histoplasmosis; Humans; Mycoses; Nocardia Infections; Penicillins; Pharmacology; Sporotrichosis; Stilbamidines; Sulfamerazine; Tetracycline

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Humans; Iodides; Lung Diseases, Fungal; Nocardia Infections; Penicillin G; Sporotrichosis; Stilbamidines; Sulfonamides; Toxicology

Topics: Amphotericin B; Brain Diseases; Cryptococcosis; Cryptococcus; Diagnosis; Diagnosis, Differential; Humans; Lung Diseases; Lung Diseases, Fungal; Meninges; Pathology; Physiology; Sepsis

Topics: Amphotericin B; Central Nervous System; Cerebrospinal Fluid; Cryptococcosis; Diagnosis, Differential; Humans; Meningoencephalitis; Mexico; Prognosis

Topics: Amphotericin B; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus; Cytodiagnosis; Diagnosis, Differential; Drug Therapy; Humans; Lung Diseases, Fungal; Meningitis; Radiography, Thoracic; Skin Diseases; Toxicology

Topics: Amphotericin B; Blood; Blood Chemical Analysis; Blood Urea Nitrogen; Creatine; Creatinine; Cryptococcosis; Drug Therapy; Hematocrit; Histoplasmosis; Kidney Calculi; Kidney Diseases; Pathology; Phenolphthaleins; Potassium; Sodium; Sodium, Dietary; Toxicology; Urea; Urine

Topics: Amphotericin B; Child; Clinical Laboratory Techniques; Cryptococcosis; Cryptococcus; Diagnosis, Differential; Drug Therapy; Fever; Humans; Leukemia; Leukemia, Lymphoid; Lung Diseases; Lung Diseases, Fungal; Lymphadenitis; Meningitis; Radiography; Sulfadiazine

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Blood Proteins; Cryptococcosis; Drug Therapy; gamma-Globulins; Lagomorpha; Mice; Pharmacology; Rabbits; Research

Topics: Amphotericin B; Brain Diseases; Cryptococcosis; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Meningitis

Topics: Adolescent; Amphotericin B; Cryptococcosis; Drug Therapy; HMGB1 Protein; Humans; Meningitis

Topics: Amphotericin B; Brain Diseases; Cryptococcosis; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Meningitis

Topics: Amphotericin B; Blood Chemical Analysis; Cerebrospinal Fluid; Cryptococcosis; Diagnosis; Drug Therapy; Humans; Meningitis; Polysaccharides; Polysaccharides, Bacterial; Prognosis; Rabbits

Topics: Amphotericin B; Cryptococcosis; Drug Therapy; Geriatrics

Topics: Amphotericin B; Cryptococcosis

Topics: Amphotericin B; Cryptococcosis; Humans; Lung Diseases; Lung Diseases, Fungal; Pneumonectomy

Topics: Amphotericin B; Cryptococcosis; Encephalitis; Humans; Isoniazid; Meningoencephalitis; Streptomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Amphotericin B; Cryptococcosis; Humans; Injections, Intraventricular; Lung Diseases; Lung Diseases, Fungal; Meningitis; Pathology; Radiography, Thoracic

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