amphotericin-b and Meningitis

The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series.. Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease.. We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs.. We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole.. Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Topics: Adult; Antifungal Agents; Central Nervous System; Female; Histoplasmosis; HIV Infections; Humans; Hydrocephalus; Itraconazole; Male; Meningitis; Vasculitis; Young Adult

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

This article summarizes the diagnosis and treatment of coccidioidal meningitis (CM) and its complications. An overview of current and prospective pharmacologic treatment options and monitoring parameters is provided. A consensus has not been reached regarding universally accepted therapeutic serum levels for azoles because of insufficient evidence. We describe the preferred therapeutic drug level ranges that our institution uses to monitor azole therapy.. Ho et al. described the preparation and administration of intrathecally delivered amphotericin B deoxycholate. Thompson et al. described possible benefits of controversial adjuvant corticosteroid therapy for secondary prevention of vasculitic infarction secondary to CM. CM was universally fatal until the advent of intrathecal amphotericin B deoxycholate therapy, the introduction of which changed the natural history of the disease in much the same way as penicillin changed the natural history of bacterial meningitis. Although there was still significant morbidity, survival rates drastically increased to approximately 70%. The introduction of azole therapy has decreased the side effects and burden of treatment but without a significant change in CM-related mortality and morbidity compared with the use of intrathecal amphotericin B deoxycholate therapy.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Cognitive Dysfunction; Deoxycholic Acid; Disease Management; Drug Combinations; Humans; Hydrocephalus; Injections, Spinal; Meningitis; Prospective Studies; Treatment Outcome

Coccidioidal meningitis (CM) is a devastating complication of coccidioidomycosis. Since the late 1950s, intrathecal (IT) amphotericin B deoxycholate (AmBd) has been successfully used to treat and often cure this disease, reducing mortality rates from 100% to approximately 30%. The introduction of azoles further revolutionized the treatment of coccidioidal infections. However, IT AmBd remains the only known curative option in the management of CM. While the use of IT AmBd is well described in many articles, few discuss the actual methods behind preparation, titration, and dosing strategies utilized. The practitioners at Kern Medical (Bakersfield, California) have >60 years of experience in the utilization of IT AmBd and the treatment of CM. This article describes the practice experience in the treatment of CM, preparation of IT AmBd, and the different dosing strategies used in regard to route of administration (ie, cisternal, lumbar, ventricular).

Topics: Amphotericin B; Antifungal Agents; Coccidioidomycosis; Humans; Injections, Spinal; Meningitis

Candida species, including Candida dubliniensis, are a rare cause of meningitis. Herein, we report the second case of C. dubliniensis meningitis in a 49-year-old man with a history of hepatitis C virus-related cirrhosis, substance use disorder, and recent exposure to intravenous antibiotic therapy, presenting with confusion, abnormal gait, and urinary incontinence. Magnetic resonance imaging (MRI) of the brain showed marked hydrocephalus and leptomeningeal enhancement. Initial cerebrospinal fluid (CSF) studies were concerning for bacterial meningitis, although cultures were negative. Despite empiric treatment with broad-spectrum antibiotics, the patient's mental status declined. The diagnosis of C. dubliniensis meningitis was not made until the third lumbar puncture. The patient was treated with liposomal amphotericin B and flucytosine. Despite improvement of hydrocephalus on MRI of the brain and sterilization of CSF, the patient's mental status declined and he expired. This case highlights the difficulty in the diagnosis of C. dubliniensis meningitis as multiple lumbar punctures may be necessary. C. dubliniensis meningitis should be considered in the differential diagnosis for a patient with risk factors such as end-stage liver disease, human immunodeficiency virus infection, recent chemotherapy, substance use disorders, and recent broad-spectrum antibiotic use. A high index of suspicion is necessary as delay in initiation of therapy is associated with high mortality. The optimal treatment strategy has not been determined.

Topics: Amphotericin B; Antifungal Agents; Brain; Candida; Candidiasis; Cerebrospinal Fluid; Fatal Outcome; Flucytosine; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Magnetic Resonance Imaging; Male; Meningitis; Middle Aged; Substance-Related Disorders

Prior to the 1950s no effective therapy for coccidioidomycosis existed. The advent of amphotericin B ushered in the therapeutic era for coccidioidomycosis. Until this time amphotericin B and its lipid congeners have been regarded as the "gold standard" of therapy for severe pulmonary and disseminated coccidioidomycosis. The availability of azoles and later triazoles for the past three decades have relegated the amphotericins into a rescue mode, used mainly in widely disseminated cases, azole intolerance, or when there are contraindications to Azoles, such as pregnancy. In meningitis the intrathecal use of amphotericin B is still used frequently by some clinicians alone or with a triazole. The newer lipid preparations, while more expensive, have significantly reduced toxicity, particularly nephropathy.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Female; Humans; Kidney Diseases; Lipids; Meningitis; Pregnancy; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antifungal Agents; Brain; Brain Neoplasms; Child, Preschool; Diagnosis, Differential; Female; Humans; Meningitis

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

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, 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

Coccidioidomycosis is a highly variable disease. Initial respiratory tract infection can lead to self-limited pneumonia, pulmonary complications, and extrapulmonary disease. The early infection requires no therapy, except in immunosuppressed patients and other selected patients. Treatment for pulmonary complications may include surgery for cavities or pyopneumothorax (resulting from rupture of a cavity) and antifungal therapy for chronic pneumonia. The majority of extrapulmonary disease occurs in the skin, bones and joints, or meninges and is an indication for treatment with antifungal agents and sometimes adjunctive surgery. Meningitis is a particularly serious consequence of dissemination and currently is best treated with intrathecal instillation of antifungal agents. Antifungal agents useful in the treatment of coccidioidomycosis are amphotericin B, which is administered intravenously and is relatively toxic, and ketoconazole, which is administered orally and whose toxicities are less serious and reversible. Because studies to compare the efficacy of these two drugs have not been performed, selecting between them for use in individual patients is most rationally based on the pharmacologic differences, which lend themselves to different clinical settings. In future years, new antifungal agents will likely be available, some of which will offer significant advantages over present therapies. Itraconazole is an imidazole related to ketoconazole, which appears to be effective and possibly less toxic than ketoconazole. Fluconazole, another imidazole, has broad antifungal activity, a long serum half-life, and excellent penetration into the cerebrospinal fluid. Thus, the pharmacology of this agent would appear ideal for use in treating coccidioidal meningitis. In addition, other compounds with different modes of action are now under investigation in preclinical studies. It is therefore likely that continued improvements will occur in the coming years in the treatment of this disease.

Topics: Amphotericin B; Coccidioidomycosis; Humans; Ketoconazole; Lung Diseases, Fungal; Meningitis

Topics: Amphotericin B; Candida; Candidiasis; Catheters, Indwelling; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Meningitis

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

Disseminated coccidioidomycosis should be considered as a diagnostic possibility whenever a patient has visited or resides in an endemic coccidioidal area and has a history of fever, skin rash, persistent pulmonary symptoms, bone pain, headache, or confusion. Imaging of this multisystem disease, especially of the lung, bone, and central nervous system, shows various protean manifestations that can simulate many infectious entities. The radiographic, scintigraphic, computed tomographic, or sonographic findings of this disease may be helpful in diagnosis, prognosis, and treatment follow-up in patients with disseminated coccidioidomycosis.

Topics: Amphotericin B; Angiography; Cerebral Ventriculography; Coccidioidomycosis; Ependymoma; Humans; Hydrocephalus; Knee; Lung Diseases, Fungal; Meningitis; Myelography; Radionuclide Imaging; Tomography, X-Ray Computed

Topics: Amphotericin B; Arthritis, Infectious; Coccidioidomycosis; Eosinophilia; Erythema; Erythema Multiforme; Erythema Nodosum; Ethnicity; Female; Humans; Liver Diseases; Lung Diseases, Fungal; Meningitis; Miconazole; Osteomyelitis; Pregnancy; Pregnancy Complications, Infectious; Skin Diseases, Infectious; Tenosynovitis; Transfer Factor; United States

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

Seven patients with Candida meningitis are reported. These 7, plus 21 previously cited cases, were reviewed. This infection arose by two distinct mechanisms: hematogenous dissemination and direct inoculation. Recent antibiotic therapy, corticosteroid administration and severe underlying diseases were important predisposing factors. Fever, meningismus, elevated CSF pressures and localizing neurologic signs were commonly noted. Organisms were seen on gram-stain of CSF in only 43% of cases. Mortality rate in patients receiving inadequate or no antifungal therapy was high (greater than 90%), while those patients given appropriate antifungal drugs, especially intravenous amphotericin B, had a significantly lower mortality rate (38%). Several factors associated with poor prognosis were delineated in this study: diagnostic interval after symptomatic onset longer than two weeks, CSF glucose levels below 35 mg/100 ml and presence of intracranial hypertension and focal neurologic deficits.

Topics: Amphotericin B; Candidiasis; Cerebrospinal Fluid Shunts; Child, Preschool; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Middle Aged; Prognosis

Topics: Amphotericin B; Animals; Bicarbonates; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Infusions, Parenteral; Injections, Intra-Articular; Injections, Intravenous; Injections, Spinal; Kidney; Mannitol; Meningitis; Mycoses; Rifampin

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: Amphotericin B; Coccidioidomycosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Methods; Mycoses

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

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

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: Adolescent; Amphotericin B; Animals; Cattle; Female; Humans; Infections; Meningitis; Prototheca

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of

Topics: Amphotericin B; Antifungal Agents; Antitubercular Agents; Ascomycota; Brain; Brain Abscess; Diagnosis, Differential; Humans; Male; Meningitis; Meningitis, Fungal; Middle Aged; Phaeohyphomycosis; Steroids; Tuberculosis, Meningeal; Voriconazole

We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement.

Topics: Abdominal Pain; Adult; Amphotericin B; Antifungal Agents; Biopsy; Bone Marrow; Dexamethasone; Diagnosis, Differential; Drug Therapy, Combination; Encephalitis, Viral; Etoposide; Female; Fever; Histoplasma; Histoplasmosis; Humans; Invasive Fungal Infections; Lymphohistiocytosis, Hemophagocytic; Meningitis; Nausea; Treatment Outcome

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

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

Intrathecal amphotericin B deoxycholate (AmB-d) can be prescribed as an adjunct to systemic therapy for severe or recalcitrant cases coccidioidal meningitis. Recently intravenous (IV) Liposomal amphotericin B (L-AmB) has been recommended as monotherapy therapy for refractory coccidioidal meningitis based on its advantages over (AmB-d), however, its intrathecal use has not been reported. Moreover, there is nothing in the literature quantifying clinical improvement with objective laboratory data in human patients. Consequently, there are no guidelines on how to monitor regularly for improvement of coccidioidal meningitis with treatment of intrathecal L-AmB. The present case addresses both of these. We report intrathecal use of L-AmB for refractory coccidioidal meningitis. Our data demonstrate that there is a correlation between clinical improvement and a decrease in cerebrospinal fluid (CSF) white blood cells (WBC's), protein, and coccidioidal titers with treatment of intrathecal L-AmB with serial collection of CSF studies at the same site, in our case via collection through an external ventricular drain (EVD). As a result, one may postulate that serial CSF collection can be used to monitor the treatment of coccidioidal meningitis; however this case also addresses the risk of developing ventriculitis with sustained EVD placement.

Topics: Adult; Amphotericin B; Antifungal Agents; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Humans; Injections, Spinal; Male; Meningitis

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Antifungal Agents; Candida glabrata; Candidiasis; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Erythrocytes; Meningitis; Mice; Mice, Inbred BALB C; Micelles; Nanoparticles; Polyethylene Glycols; Rabbits; Receptors, Transferrin; Transferrin

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV-infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological work-up showed that this is the first report of R. glutinis isolation from our institute.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; HIV Infections; Humans; Male; Meningitis; Middle Aged; Retrospective Studies; Rhodotorula

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Brain Damage, Chronic; Brain Edema; Child; Delayed Diagnosis; Deoxycholic Acid; Diagnostic Errors; Drug Combinations; Histoplasma; Histoplasmosis; Humans; Hydrocephalus; Immunocompetence; Itraconazole; Liposomes; Male; Meningitis; Meningitis, Viral; Prognosis; Stroke, Lacunar; Tuberculosis, Meningeal; Ventriculoperitoneal Shunt

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

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

Despite the advent of new antifungal agents, coccidioidal meningitis (CM) remains a difficult-to-treat condition with significant morbidity and mortality. In this study we directly compare the clinical presentation and management of patients with Coccidioides immitis meningitis in the azole era (after 1980) to that of a cohort of patients from the pre-azole era. We reviewed 30 CM cases seen at 3 Los Angeles hospitals between the years 1993 to 2008 ("2008 cohort") and compared them to 31 patients ("1980 cohort") described by Bouza et al in a previous study. The demographics and clinical presentation of patients in the 2008 cohort were similar to those of the 1980 cohort except for a higher incidence of Hispanic patients (2008: 53% vs. 1980: 6%) and a greater percentage of patients with underlying, predisposing clinical conditions (2008: 66% vs. 1980: 32%). Ten patients in the 2008 cohort had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a condition not reported in the earlier study. Laboratory findings were similar between the 2 groups except for a lower incidence of peripheral leukocytosis and eosinophilia in the 2008 group.There were marked differences in drug treatment between the 2 eras. In the 2008 cohort, 29 patients received fluconazole therapy: 13 were treated with fluconazole monotherapy, and 16 received a combination of fluconazole and intravenous amphotericin B. Although almost all patients (29/31) in the 1980 cohort received intrathecal amphotericin B, only 3 patients in the 2008 study received amphotericin B via this route. With respect to complications of CM, a similar percentage of patients in each cohort developed complications such as stroke and hydrocephalus. The 2008 cohort (40%) had similar mortality compared to patients in the 1980 study (39%); survivors in both groups experienced significant impairment of activities of daily living. Although recommended as first-line therapy for CM, azole-based therapies are not curative and do not necessarily prevent complications associated with the disease.CM remains a serious illness with a high rate of morbidity and mortality. Immunocompromised individuals, especially those with HIV/AIDS, are at special risk for CM and represent a greater share of the overall population with this condition. Despite the clear advantages of azole treatment in CM, new therapeutic approaches are needed to provide definitive cure and to reduce the need for long-term suppressive therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Coccidioides; Coccidioidomycosis; Enzyme-Linked Immunosorbent Assay; Female; Fluconazole; Humans; Hydrocephalus; Male; Meningitis; Middle Aged; Radiography, Thoracic; Young Adult

A rare case of Prototheca wickerhamii meningitis is reported in a patient without any underlying immunodeficient condition. Wet-mount microscopy and culture of cerebral spinal fluid specimens, along with temperature resistance, cycloheximide tolerance, carbohydrates assimilation, including API 20C AUX tests of the isolated etiologic agent were performed. In addition, transmission and scanning electron microscopy studies and in vitro antifungal susceptibility tests were conducted. Through the combination of these investigations, the isolate was identified as P. wickerhamii and the patient was successfully treated with intravenous amphotericin B and itraconazole. This is the first detailed report of meningitis caused by P. wickerhamii in China.

Topics: Adult; Amphotericin B; China; Humans; Infections; Itraconazole; Male; Meningitis; Prototheca

Extrapulmonary manifestations of tuberculosis involving the central nervous system (CNS) due to haematogenous spread are not a rare entity. It presents as meningitis or tuberculoma. Tuberculoma is a granulomatous inflammatory process mimicking a neoplasm radiologically, so usually a biopsy is performed.. Our study consisted of 23 pathologically proven cases of tuberculomas between 1988 and 2003. Patients were discussed clinically, radiologically and histologically. Headache, fever, weight loss and weakness are the most common clinical manifestations. Our patient's ages vary from 3 to 67 years with a mean of 31.8 years. Ninety-five percent of patients had bad social, economic and nutritional conditions. None of them were infected by human immunodeficiency virus (HIV). All patients had similar contrast-enhancing lesions radiologically. The majority of tuberculomas were located supratentorially. Only one patient presented two foci of (cerebral and cerebellar) tuberculomas. Nineteen tuberculomas were intracerebral; two were located in the cerebellum and one was intramedullary. Among those lesions, one cavernous sinus tuberculoma and one sellar tuberculoma were identified. Only two patients underwent stereotactic biopsy and 21 patients underwent surgical excision. Histopathologic examination revealed granulomatous inflammation with central caseous necrosis in all patients.. Diagnosis of tuberculoma can be difficult, and in most of our cases, the clinical diagnosis was 'neoplasm'. For this reason, clinicians must always be aware of it and consider it in the differential diagnosis of central nervous system mass lesions.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Infective Agents; Brain Diseases; Child; Child, Preschool; Diagnosis, Differential; Female; Fever; Headache; Humans; Magnetic Resonance Imaging; Male; Meningitis; Middle Aged; Necrosis; Retrospective Studies; Socioeconomic Factors; Tuberculoma, Intracranial

The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P < or =0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the trea

Topics: Amphotericin B; Animals; Antifungal Agents; Body Temperature; Body Weight; Brain; Cerebrospinal Fluid; Coccidioidomycosis; Leukocyte Count; Male; Meningitis; Motor Activity; Posture; Rabbits; Spinal Cord; Survival Analysis

Acute amebic meningoencephalitis caused by free-living amebae naegleria fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinal fluid (CSF) and treated with amphoterecin B, rifampicin and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival.

Topics: Adult; Amebiasis; Amebicides; Amphotericin B; Animals; Antiprotozoal Agents; Drug Therapy, Combination; Female; Humans; Meningitis; Naegleria fowleri; Ornidazole; Rifampin

Bipolaris spicifera, one of the darkly pigmented (dematiaceous) fungi commonly found in soil, is an uncommon cause of infection in humans and an unusual cause of meningitis and nosocomial infections. An 18-y-old boy who experienced meningitis with this micro-organism after acoustic neuroma resection was successfully treated with amphotericin B.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Fungi; Humans; Itraconazole; Male; Meningitis; Microbial Sensitivity Tests; Neuroma, Acoustic; Postoperative Complications; Skull Base Neoplasms; Treatment Outcome

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

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: Amebiasis; Amphotericin B; Animals; Antiprotozoal Agents; Child; Humans; Hydrocephalus; Injections, Spinal; Male; Meningitis; Naegleria fowleri

A case of an Italian AIDS patient who developed both meningitis and cerebral mass lesion as a final relapse of disseminated histoplasmosis is reported. Central nervous system (CNS) involvement occurred while the patient was receiving both amphotericin B and itraconazole as maintenance therapy, thus indicating the difficulty of eradicating histoplasmosis in patients with AIDS.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Fatal Outcome; Histoplasma; Histoplasmosis; Humans; Italy; Itraconazole; Male; Meningitis

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

A case of chronic meningitis caused by the achloric alga Prototheca wickerhamii is described, which has persisted for more than 6 years despite treatment with various antifungal agents. For the last year no treatment has been given, but the patient has no complaints.

Topics: Adult; Amphotericin B; Antifungal Agents; Chronic Disease; Humans; Infections; Male; Meningitis; Prototheca; Radiography

A 10-year-old boy had been suffering from kala-azar (visceral leishmaniasis) for two and a half years. He failed to respond to all known anti-leishmanial treatment regimens. Even the drastic step of splenectomy failed to cure him. In November 1991, he presented with symptoms of meningitis. A diagnostic lumbar puncture revealed leishmanial amastigotes in his cerebrospinal fluid. The patient was finally cured with a course of amphotericin B, a drug known to cross the blood-brain barrier.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Cerebrospinal Fluid; Child; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Meningitis

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Cerebrospinal Fluid; Child; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Meningitis; Splenectomy

Intrathecal administration of amphotericin B is the best method of eradicating intracranial fungal infections. The Ommaya reservoir provides an easy and practical method for fungicidal medication administration. Treatment of coccidioidomycosis with amphotericin B may be accomplished via an Ommaya reservoir. Astute nursing care is essential to prevent complications associated with this procedure.

Topics: Amphotericin B; Brain Abscess; Catheters, Indwelling; Cerebral Ventricles; Coccidioidomycosis; Humans; Injections, Spinal; Male; Meningitis; Middle Aged; Patient Care Planning

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

A case of candida meningitis occurring in a child treated for a lymphoma is reported. Diagnosis was made with Candida albicans culture in the CSF. Blood cultures were negative. Cerebral CT scan was normal. No other localization was found. The child was successfully treated by amphotericin B (initially with 5-fluorocytosin). Fluconazole was continued orally later on. This case is noteworthy by the absence of other localization, the favourable evolution and its occurrence in childhood. The therapeutic attitude and prevention are discussed.

Topics: Abdominal Neoplasms; Adolescent; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Fluconazole; Follow-Up Studies; Humans; Immunosuppression Therapy; Lymphoma, B-Cell; Male; Meningitis; Neoplasm Recurrence, Local

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Confidence Intervals; Cryptococcosis; Fluconazole; Humans; Male; Meningitis; Prospective Studies; Prostatic Diseases; Recurrence

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

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

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Carriers; Humans; Liposomes; Male; Meningitis

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

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Arizona; California; Coccidioidomycosis; Dermatomycoses; Female; Follow-Up Studies; HIV Infections; Humans; Ketoconazole; Leukocyte Count; Liver Diseases; Lung Diseases, Fungal; Lymphatic Diseases; Male; Meningitis; Retrospective Studies; T-Lymphocytes, Helper-Inducer

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

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

Topics: Adult; Amphotericin B; Cryptococcosis; Fluconazole; Flucytosine; Humans; Male; Meningitis

Trichosporon beigelii (Trichosporon cutaneum) was identified as the causative agent of chronic meningitis in a 15-year-old boy with acute lymphocytic leukaemia. After a neutropenic episode following cytostatic treatment and itraconazole therapy as prophylaxis, cerebrospinal fluid (CSF) samples yielded growth of Trichosporon beigelii. Treatment with amphotericin B, flucytosine and high doses of fluconazole was followed by clinical improvement, although CSF pleocytosis remained. The cross-reactivity between Cryptococcus neoformans and Trichosporon beigelii in a cryptococcal antigen latex test was used as a means of diagnosis in CSF and serum samples.

Topics: Adolescent; Amphotericin B; Chronic Disease; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis; Mycoses; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporon

Topics: Administration, Oral; Aged; Alberta; Amphotericin B; Arizona; Coccidioides; Coccidioidomycosis; Female; Fluconazole; Humans; Injections, Spinal; Male; Meningitis; Travel

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

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

A case of coccidioidal meningitis following an open-head injury is presented. A 6-year-old boy was ejected from a motor vehicle as it was driven over a cliff, resulting in a severe open-skull fracture with grossly contaminated wounds. The accident occurred in an area in which coccidioidomycosis is endemic, and the causative agent, Coccidioides immitis, is found in high concentration in the soil. In addition to fracture reduction, the child received a course of intrathecal and intravenous amphotericin and achieved a satisfactory clinical response.

Topics: Amphotericin B; California; Child; Coccidioidomycosis; Craniocerebral Trauma; Humans; Male; Meningitis; Tomography, X-Ray Computed; Wound Infection

Topics: Adult; Amphotericin B; Candidiasis; Female; HIV Seropositivity; Humans; Ketoconazole; Meningitis

Topics: Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Meningitis

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 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

A woman with coccidiodal meningitis had two successive pregnancies and was treated with intrathecal amphotericin B. The outcome was successful.

Topics: Adult; Amphotericin B; Coccidioides; Coccidioidomycosis; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Pregnancy; Pregnancy Complications, Infectious; Recurrence

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

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

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: Adult; Amphotericin B; Anemia, Aplastic; Cryptococcosis; Flucytosine; Humans; Male; Meningitis

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

Fifteen patients with coccidioidal meningitis were treated with high doses of ketoconazole for up to 4 years. Five patients were treated with ketoconazole alone. One clinically failed, one developed hepatotoxicity, and three achieved remission of meningitis. One patient received intrathecal AMB in addition to ketoconazole for only 2 weeks before continuing on ketoconazole alone. He improved, but discontinued ketoconazole because of nausea and vomiting, and suffered a lethal relapse. Nine patients received ketoconazole in combination with prolonged courses of intrathecal AMB. Two patients were failures from nausea and vomiting, and the remaining seven either improved or experienced remission. The clinical responses appeared to be similar in patients receiving high-dose ketoconazole, either alone or combined with AMB, suggesting that there is no clinically significant antagonism of the drugs. Nausea and vomiting are significant limitations of high-dose ketoconazole. Ketoconazole alone is effective in some patients with coccidioidomycotic meningitis.

Topics: Amphotericin B; Coccidioidomycosis; Drug Therapy, Combination; Humans; Ketoconazole; Leukocyte Count; Meningitis

Topics: Amphotericin B; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Infant, Newborn; Infusions, Intravenous; Meningitis; Mycoses

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Meningitis

The mortality related to coccidioidal meningitis (CM) has been reduced since the introduction of amphotericin B therapy, but children with CM continue to suffer significant morbidity. Some of this is related to the toxicity of the drug. We report nine children with CM treated with orally administered ketoconazole and intraventricularly administered miconazole. Four of them had been treated initially with amphotericin B with resultant failure in one and severe toxicity in all four. The other five children were treated only with imidazoles. All nine children had evidence of ventriculitis at the time of diagnosis and had ventriculoperitoneal shunts inserted for control of increased intracranial pressure. There was no relapse or recrudescence of CM in a follow-up period of 32 to 90 months on imidazole therapy. The coccidioidal complement-fixation antibody titers in the cerebrospinal fluid of the lateral ventricle became negative in all children 3 to 51 months after diagnosis (mean, 17 months). The serum antibody titers demonstrated a 16- to 256-fold decrease from their maximal levels. Four children are still receiving intraventricular miconazole whereas the others have not received miconazole for an average of 51 months. Therapy with the imidazoles was well-tolerated. The main morbidity was related to the shunts required for control of increased intracranial pressure. There was no evidence of hepatic toxicity and no clinical evidence of adrenal insufficiency although transient adrenal suppression was demonstrated at 4 but not at 24 hours after ketoconazole administration.

Topics: Administration, Oral; Amphotericin B; Cerebrospinal Fluid Shunts; Child; Child, Preschool; Coccidioidomycosis; Combined Modality Therapy; Female; Humans; Infant; Injections, Intravenous; Injections, Intraventricular; Injections, Spinal; Ketoconazole; Male; Meningitis; Miconazole; Peritoneal Cavity

Topics: Amphotericin B; Coccidioidomycosis; Humans; Injections, Subcutaneous; 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: Agranulocytosis; Amphotericin B; Anemia, Hemolytic, Autoimmune; Cryptococcosis; Female; Flucytosine; Humans; Meningitis; Middle Aged; Neutropenia; Prednisolone; Purpura, Thrombocytopenic

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Drug Administration Schedule; Follow-Up Studies; Humans; Meningitis; Recurrence

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

Male ICR mice were challenged intracerebrally with endospores of Coccidioides immitis and then treated with water (control), fluconazole, amphotericin B (Fungizone), or ketoconazole (Nizoral). All three drugs markedly prolonged survival, and all three drugs lowered brain colony counts of C. immitis. Survival of mice treated orally with fluconazole at the high dose was longer than in the ketoconazole treated group. Amphotericin B was more efficacious than fluconazole. Further investigations are needed to determine the efficacy of fluconazole in treatment of coccidioidal meningitis.

Topics: Amphotericin B; Animals; Antifungal Agents; Coccidioides; Coccidioidomycosis; Fluconazole; Ketoconazole; Male; Meningitis; Mice; Mice, Inbred ICR; Triazoles

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

Topics: Amphotericin B; Candida albicans; Cryptococcus neoformans; Cytosine; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Meningitis

We have reported an unusual case of Candida glabrata meningitis causing acute changes in mental status in a chronically ill, elderly patient with non-insulin-dependent diabetes mellitus. Candida glabrata was identified by Gram stain, culture, and fermentation pattern from the CSF. Although the patient died of foreign body aspiration, an excellent clinical response was initially obtained with amphotericin B and 5-flucytosine. This is the first report of a symptomatic Candida glabrata meningitis.

Topics: Aged; Amphotericin B; Candidiasis; Chronic Disease; Drug Therapy, Combination; Female; Flucytosine; Humans; Meningitis

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

Eleven patients with coccidioidal meningitis were treated with high individual doses (1.0 to 1.5 mg) of intrathecal amphotericin B mixed with 25 to 50 mg of hydrocortisone in an attempt to reach a dose of 12 mg per month for at least two consecutive months. Patients received a mean intrathecal dose of amphotericin B of 82 mg (range, 40 to 157 mg) and 2.4 g intravenously (range, 1.0 to 3.5 g). No deaths related to disease or treatment occurred, and overall survival was 91% during an average follow-up period of 75 months (range, 30 to 137 months). Comparative analysis with eight well-known series in the literature reveals that our survival rate and follow-up time are significantly greater than the more recent series (1977-1981). Rank correlation and linear regression showed that the mean intrathecal dose of amphotericin B used in all series corresponds well with mean survival time. Our clinical results and analysis of the literature suggest that intrathecal amphotericin B administered at a high dose rate of 0.75 mg (or greater) three times per week promptly reaching 20 mg and a total surpassing 40 mg is associated with significantly enhanced survival rates.

Topics: Adult; Amphotericin B; Coccidioidomycosis; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Middle Aged

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

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

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

The incidence of candidiasis meningitis in infants has lately increased. This required choosing of the dose and regimen for the use of amphotericin B, the only drug effective in the treatment of generalized mycoses. The antibiotic levels in the blood and CSF were determined in 14 infants at various periods after discontinuation of intravenous drip infusion of amphotericin B. It was shown that the therapeutic concentrations of the antibiotic in the blood were attained when it was administered in a dose of 120-200 units/kg twice a day. For attaining the therapeutic concentrations of the antibiotic in the CSF, daily endolumbar administration of amphotericin B in a dose more than 10 units in addition to its intravenous drip infusions was required. Therefore, the tactics of amphotericin B use in the treatment of candidiasis meningitis in infants was developed.

Topics: Amphotericin B; Biological Availability; Blood-Brain Barrier; Candidiasis; Dose-Response Relationship, Drug; Humans; Infant; Kinetics; Meningitis

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

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

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

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

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

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Infant; Male; Meningitis

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

Subacute meningitis caused by Candida albicans was confirmed by culture and immunoserologically in a 19-year-old girl. Combined administration of amphotericin B and flucytosine only slowly affected the course of the disease despite impressive improvement in clinical symptoms. Pleocytosis (1000/mm3) in cerebrospinal fluid persisted. Falling Candida antibody titre in serum and CSF, however, pointed to an improvement in the acute infection. Treatment had to be discontinued after 42 days because of side-effects such as rigor, fever and polyuria with low concentration. Under serial clinical observations with occasional CSF punctures complete cure occurred with normal CSF findings. There was an additional and unusual neurological-otological condition of intermittent inner-ear deafness, left more than right, before treatment. Recording of early auditory evoked potentials pointed to an involvement of the cranial nerves as part of the inflammatory process.

Topics: Adolescent; Amphotericin B; Antibodies, Fungal; Candida albicans; Candidiasis; Female; Flucytosine; Humans; Meningitis

Topics: Aged; Amphotericin B; Chronic Disease; Coccidioidomycosis; Humans; Male; Meningitis; Pennsylvania

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: Amphotericin B; Candidiasis; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Meningitis; Miconazole

Topics: Adolescent; Amphotericin B; Child; Coccidioidomycosis; Female; Humans; Infant; Male; Meningitis

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Female; Flucytosine; Humans; Infant; Infant, Newborn; Male; Meningitis; Middle Aged; Prognosis

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

A case of bilateral necrotizing scleritis due to Aspergillus oryzae is reported. The patient was a former addict of intravenous narcotics treated five years previously for meningitis due to the same organism. A seeding focus in the thoracic spine was eventually found. The patient responded well to combined local and systemic therapy with amphotericin B, flucytosine, and natamycin. This represents, to the best of our knowledge, both the first reported case of ocular disease due to this species of Aspergillus and of isolated scleral, nonintraocular involvement in endogenous oculomycosis.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus oryzae; Child; Cocaine; Eye Diseases; Female; Flucytosine; Heroin; Humans; Inflammation; Injections, Intravenous; Meningitis; Natamycin; Sclera; Substance-Related Disorders

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

Topics: Amphotericin B; Animals; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Horse Diseases; Horses; Male; Meningitis

A man of 74 years of age, suffering from a left-sided ophthalmoplegia and a radiologically detected opacification of the sphenoid sinus with destruction of the bony roof of the sphenoid sinus, was operated on because a malignant tumor was suspected. A destruction of the bony walls of the sphenoid sinus was found. The histological examination of the "glue"-like "tumorous" material revealed an aspergillosis. The patient developed an aspesrgillus meningitis postoperatively. Intrathecally administered Amphotericin B led to an improvement of the meningitis, but caused a fatal renal failure. A review of the literature showed that only 7 cases of aspergillosis of the sphenoid sinus have been reported, 3 of which presented with a tumor-like destruction of the sinus. An aspergilloma of the sphenoid sinus is therefore a rare but important differential diagnosis in patients with a suspected malignancy of the infrasellar region.

Topics: Aged; Amphotericin B; Aspergillosis; Diagnosis, Differential; Humans; Male; Meningitis; Pituitary Neoplasms; Sphenoid Sinus

We present a patient with coccidioidal meningitis whose diagnosis was not confirmed until a skin biopsy was performed. Because he lived in an area where coccidioidomycosis is not endemic, his meningitis was at first attributed to tuberculosis or sarcoidosis. After a verrucous lesion from the face was biopsied and the diagnosis substantiated, the patient responded well to consolidation therapy consisting of intrathecal amphotericin B and oral ketoconazole.

Topics: Adult; Amphotericin B; Coccidioidomycosis; Dermatomycoses; Humans; Male; Meningitis

Topics: Adult; Amphotericin B; Brain Diseases; Cryptococcosis; Cytosine; Flucytosine; Humans; Male; Meningitis

Topics: Adrenal Cortex Hormones; Amphotericin B; Asthma; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Meningitis; Middle Aged; Prednisone

Topics: Adult; Amphotericin B; Candida albicans; Candidiasis; Culture Media; Humans; Male; Meningitis

Topics: Aged; Amphotericin B; Antibodies, Fungal; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Meningitis

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis; 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; Coccidioidomycosis; Female; Humans; Meningitis; Methylprednisolone

Topics: Adult; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Female; Flucytosine; Humans; Meningitis; Tuberculosis, Meningeal

Topics: Amphotericin B; Candidiasis; Child; Ethambutol; Flucytosine; Humans; Isoniazid; Male; Meningitis; Streptomycin; Tuberculosis, Meningeal

Two adult patients with CSF shunts contracted Candida albicans meningitis. In both patients, these infections were either preceded by or occurred simultaneously with bacterial meningitis. Treatment with antimicrobials alone failed to sterilize the CSF. Cure was obtained only after removal of the shunt tubes. The simultaneous or subsequent development of Candida meningitis should be considered in selected patients who do not make appropriate recovery from a bacterial meningitis, especially one that complicates shunt placement.

Topics: Acinetobacter Infections; Adult; Aged; Amphotericin B; Candidiasis; Cerebrospinal Fluid Shunts; Enterococcus faecalis; Female; Humans; Male; Meningitis; Postoperative Complications; Streptococcal Infections

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

Two patients with coccidioidal meningitis experienced transient neurologic deficits shortly after receiving intrathecal injections of amphotericin B. Continuation of treatment eventually led to a severe flaccid paraparesis with a thoracic sensory level in one patient, and a partial Brown-Séquard's syndrome in the other. Myelography was normal in both, with no evidence of arachnoiditis. Autopsy findings in the first patient showed a focal area of necrosis in the left half of the spinal cord consistent with the patient's clinical findings during life. The distribution of the lesion corresponded to the area supplied by a central sulcal artery. Amphotericin B may exert a direct toxic effect on the spinal cord or its vascular supply when given intrathecally.

Topics: Amphotericin B; Coccidiosis; Female; Humans; Injections, Spinal; Male; Meningitis; Middle Aged; Muscle Hypotonia; Myelography; Paralysis; Spinal Cord; Spinal Cord Diseases

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

Two patients with culture-negative chronic meningitis were diagnosed as having Histoplasma capsulatum meningitis based on serial serologic studies; both had antibody in the cerebrospinal fluid as well as the serum. The patients were treated successfully with amphotericin B and had favorable clinical responses. Three control patients with active histoplasmosis and positive serum serologic tests, but without meningeal involvement, did not have antibody in the cerebrospinal fluid. Patients with chronic meningitis of obscure cause should have serial serum and cerebrospinal fluid antibody studies for H. capsulatum.

Topics: Adult; Aged; Amphotericin B; Complement Fixation Tests; Female; Histoplasmosis; Humans; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Male; Meningitis; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Humans; Injections, Intravenous; Male; Meningitis; Middle Aged

Topics: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation; Flucytosine; Humans; Meningitis; Miconazole

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

This report describes a case in which an intracranial histoplasmoma was successfully treated with surgical removal and amphotericin B. This is the third reported case of its kind. The authors discuss problems of preoperative diagnosis in a patient with depressed cell-mediated immunity, and no evidence of extracerebral dissemination.

Topics: Adult; Amphotericin B; Brain Diseases; Female; Histoplasmosis; Humans; Meningitis

Topics: Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Meningitis

Topics: Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Meningitis

A patient with coccidioidal meningitis was treated with intrathecally administered amphotericin B, and an acute toxic delirium with EEG abnormalities developed. Clinical recovery followed discontinuation of therapy and paralleled EEG resolution. This complication was dose related and argues for caution when initiating intrathecal therapy with amphotericin B at doses greater than 0.025 mg.

Topics: Acute Disease; Adult; Amphotericin B; Coccidioidomycosis; Electroencephalography; Humans; Injections, Spinal; Male; Meningitis; Psychoses, Substance-Induced

The incidence of Candida meningitis in the neonatal period is increasing, and 63% of reported patients have either died or are mentally retarded. We report a newborn with Candida meningitis and arthritis who did well after treatment with intravenous and intrathecal amphotericin B, along with oral flucytosine.

Topics: Administration, Oral; Amphotericin B; Arthritis, Infectious; Candidiasis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infusions, Parenteral; Injections, Spinal; Male; Meningitis

Candida albicans meningitis was diagnosed in a 45-day-old premature infant whose birth weight was 1,616 gm. Symptoms consisted of poor weight gain and poor suckling. The combined use of amphotericin B and 5-fluorocytosine (5-FC) resulted in negative CSF cultures after 12 days of therapy. Amphotericin B was given for 45 days (total 83 mg) and 5-FC for 60 days (total 19 mg). Only one other premature infant has been reported in the literature who had similar treatment. A review of Candida meningitis diagnosed before death in 11 other infants less than 1 year of age is presented.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Male; Meningitis

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

A patient with disseminated coccidioidomycosis initially had pulmonary and skin manifestations and survived for 14 years before dying of meningitis due to Coccidioides immitis. In addition to several courses of amphotericin B therapy the patient received injections of transfer factor derived from appropriate donors and miconazole nitrate therapy. The immunologic defence mechanisms of the patient during the course of his disease were studied and the possibility of a cell-mediated immunologic defect, potentially reversible by transfer factor, was demonstrated.

Topics: Adult; Amphotericin B; Coccidioidomycosis; Dermatomycoses; Humans; Immunity, Cellular; Male; Meningitis; Miconazole; Prognosis; Transfer Factor

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

Meningitis due to Candida albicans was successfully treated in a 1.1 kg premature infant using combined antifungal therapy of amphotericin B for three weeks and 5-fluorocytosine for four months. Hydrocephalus and profound psychomotor retardation were present one year later. Psychomotor retardation, aqueductal stenosis and hydrocephalus were found to be common in a review of 16 previously reported cases of central nervous system (CNS) candidiasis in newborn infants. The diagnosis and institution of therapy were frequently delayed, and the mortality rate was 29% in the 17 patients reviewed here. The subacute course, lack of clinical findings, variable cerebrospinal fluid (CSF) findings, negative CSF cultures due to low concentrations of organisms, slow in vitro growth of C. albicans and misinterpretation of positive cultures as contaminants are factors frequently leading to delayed diagnoses. Using combination therapy, it should be possible to use lower doses and shorter courses of amphotericin B therapy for C. albicans meningitis in the newborn infant.

Topics: Adolescent; Amphotericin B; Candidiasis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Follow-Up Studies; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Male; Meningitis; Pregnancy; Psychomotor Disorders

Miconazole at dosages up to 30 mg/kg/day was given intravenously to seven patients with complicated courses of disseminated coccidioidomycosis. Six had received treatment with amphotericin B previously and five of these patients could be evaluated for the efficacy of the treatment. In three patients the condition failed to respond to therapy, another patient required intratracheal administration of amphotericin B later, and the fifth patient had an equivocal response to treatment. Severe phlebitis, pruritus, nausea, vomiting, hyperlipidemia, and thrombocytosis were frequent side effects. These limited unfavorable results indicate that until controlled studies demonstrate its safety and efficacy, therapy with miconazole should be reserved for highly selected patients with disseminated coccidioidomycosis who cannot receive amphotericin B.

Topics: Adult; Amphotericin B; Coccidioidomycosis; Drug Evaluation; Humans; Imidazoles; Infusions, Parenteral; Injections, Intraventricular; Lung Diseases, Fungal; Male; Meningitis; Miconazole; Middle Aged

Topics: Amphotericin B; Clotrimazole; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Meningitis; Miconazole; Mycoses; Rifampin; Thrombophlebitis

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

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Flucytosine; Humans; Male; Meningitis

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

The fungus Sporotrichum schenckii caused chronic meningitis in a 48-year-old man. Only three other firmly diagnosed cases were reported previously.

Topics: Amphotericin B; Humans; Male; Meningitis; Middle Aged; Sporotrichosis

Topics: Aged; Amphotericin B; Cryptococcosis; Humans; Male; Meningitis

Topics: Adolescent; Adult; Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Male; Meningitis

Histoplasma meningitis (HM) has been reported to occur primarily in association with disseminated histoplasmosis (DH). We report a case of histoplasma meningitis occurring in a patient with common variable hypogammaglobulinemia (CVH) in which no manifestations of DH were observed. L. L., a 66-year-old Caucasian male, clerical worker, developed occasional episodes of dizziness and tinnitus in mid-1971. During 1972, increasing frequency of these episodes and gradually progressive confusion were noted. In January 1973, vomiting, forther confusion, obnubilation, and a left central facial paresis developed and he was hospitalized. Physical examination revealed no pulmonary abnormalities, lymphadenopathy or hepatosplenomegaly. Over the ensuing 6-week evaluation, there was occasional fever to 38.5 degrees C. Chest roentgenogram was normal. Cerebral angiography suggested a mass in the left cerebellar hemisphere. EEG was diffusely slow. Multiple CSF examinations revealed: Glucose 7-18 mg/with a normal blood glucose, protein 109-256 mg/and cells 66-140 (95 + % mononuclear). Histoplasma capsulatum was cultured from CSF but not from sputum, urine, blood or bone marrow. Skin tests for PPD, histoplasmosis, coccidiodomycosis, blastomycosis, mumps, dinitrochlorobenzene and streptokinase-streptodornase were negative then and 6 months later. Histoplasma serum antibody was absent. Immunoglobulin analysis revealed IgG 430 mg %, IgA 46 mg %, and IgM 35 mg %, which with the history and skin test results suggested CVH. Treatment with 2.51 gm of amphotericin B given intravenously over a 3-month period resulted in complete reversal of all neurologic signs and clearing of the confusion. The remission has been maintained for two years. This case represents a primary infection of the CNS by histoplasma. The relationship between the HM and the CVH will be discussed.

Topics: Agammaglobulinemia; Aged; Amphotericin B; Cerebrospinal Fluid; Diagnosis, Differential; Histoplasma; Histoplasmosis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymphocytes; Male; Meningitis; Skin Tests

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: Administration, Oral; Amphotericin B; Candidiasis; Flucytosine; Humans; Imidazoles; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Miconazole

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

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

In a patient with only meningitis, a septate hypha was seen in a Langhans giant cell, and the rarely pathogenic Aspergillus oryzae was cultured from the cerebrospinal fluid. Serologic results confirmed the diagnosis. The patient responded to therapy with amphotericin B and flucytosine.

Topics: Adult; Amphotericin B; Antibodies, Fungal; Aspergillus; Aspergillus oryzae; Cerebrospinal Fluid; Female; Flucytosine; Humans; Meningitis

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Male; Meningitis

Topics: Amphotericin B; Candidiasis; Child; Child Abuse; Female; Humans; Meningitis

The combined use of amphotericin B and 5-fluorocytosine in the treatment of two children with Candida albicans meningitis is described. Therapy consisted of nine to 13 days of iv amphotericin B, combined with, or followed by six to nine weeks of oral 5-FC. Each organism was sensitive to 5-FC before starting therapy. Resistance did not develop during therapy. CSF administration was not necessary and toxic reactions were minimal and transient; neither patient has suffered a recurrence four years and 14 months, respectively, after discontinuance of therapy. The combination of short-term therapy with iv amphotericin B plus long-term oral 5-FC was successful in these two patients.

Topics: Amphotericin B; Candidiasis; Child; Child, Preschool; Cytosine; Drug Administration Schedule; Drug Therapy, Combination; Female; Flucytosine; Humans; Infant; Male; Meningitis; Microbial Sensitivity Tests

Topics: Amphotericin B; Ampicillin; Brain Abscess; Candidiasis; Cryptococcosis; Enterobacteriaceae Infections; Esophagitis; Herpes Simplex; Humans; Infections; Meningitis; Meningitis, Listeria; Mucormycosis; Neoplasms; Pharyngitis; Stomatitis; Toxoplasmosis

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

Topics: Amphotericin B; Antifungal Agents; Benzene Derivatives; Benzyl Compounds; Candida albicans; Candidiasis; Cytosine; Ethers; Fluorine; Humans; Imidazoles; Infant; Meningitis

Topics: Age Factors; Amphotericin B; Candida albicans; Candidiasis; Cerebrospinal Fluid; Humans; Infant; Meningitis

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

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

Topics: Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation; Humans; Male; Meningitis

Topics: Administration, Oral; Adult; Amphotericin B; Cryptococcosis; Cytosine; Flucytosine; Humans; Male; Meningitis

Topics: Amphotericin B; Candidiasis; Female; Fetofetal Transfusion; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Pregnancy; Twins

Topics: Amphotericin B; Child, Preschool; Coccidioidomycosis; Humans; Injections, Intravenous; Injections, Spinal; Male; Meningitis; Spinal Puncture

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: 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; Anti-Bacterial Agents; Candidiasis; Humans; Immunity; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meningitis

Topics: Amphotericin B; Cryptococcosis; Cytosine; Female; Flucytosine; Humans; Meningitis; Middle Aged

Topics: Adrenal Cortex Hormones; Amphotericin B; Coccidioidomycosis; Drug Combinations; Humans; Hydrocephalus; Immunity, Maternally-Acquired; Meningitis; Prognosis

Topics: Adult; Amphotericin B; Antifungal Agents; Autopsy; Benzyl Compounds; Brain; Coccidioides; Coccidioidomycosis; Drug Evaluation; Drug Resistance, Microbial; Ethers; Humans; Imidazoles; Injections, Intravenous; Male; Meningitis

Topics: Administration, Oral; Amphotericin B; Arrhythmias, Cardiac; Brain Diseases; Cytosine; Flucytosine; Gastrointestinal Diseases; Humans; Hypokalemia; Injections, Intravenous; Injections, Spinal; Intestinal Perforation; Kidney Diseases; Meningitis; Mycoses; Paralysis; Radiculopathy; Vision Disorders

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; Antifungal Agents; Arthritis, Infectious; Candidiasis; Cytosine; Drug Resistance, Microbial; Drug Therapy, Combination; Endophthalmitis; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis; Osteomyelitis; Pyelonephritis; Radiography; Recurrence; Sepsis

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: Amphotericin B; Candidiasis; Child, Preschool; Encephalitis; Humans; Hypersensitivity, Delayed; Immunity, Maternally-Acquired; Immunotherapy; Infant; Meningitis

Topics: Adult; Amphotericin B; Biopsy; Cholangitis; Cryptococcosis; Diagnostic Errors; Flucytosine; Granuloma; Hepatitis; Humans; Liver; Male; Meningitis; Neurologic Manifestations

Topics: Amphotericin B; Candida albicans; Candidiasis; Child; Electroencephalography; Eye Diseases; Fever; Fundus Oculi; Humans; Inflammation; Injections, Intravenous; Male; Meningitis; Parenteral Nutrition; Visual Acuity

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: 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: 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: Adult; Amphotericin B; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Female; Humans; Meningitis; Pregnancy; Puerperal Disorders

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Meningitis

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

Topics: Amphotericin B; Catheterization; Cerebral Ventricles; Cerebrospinal Fluid; Humans; Injections, Spinal; Leukemia; Meningitis; Methods; Subarachnoid Space

Topics: Adolescent; Amphotericin B; Arachnoiditis; Coccidioidomycosis; Female; Humans; Injections, Spinal; Male; Meningitis; Staphylococcal Infections; Sterilization

Of two patients who had acute neurologic damage from cisternal punctures, one died 17 hours following a tap which produced major subarachnoid hemorrhage, the other patient recovered from probable brain stem infarction associated with cisterna magna amphotericin injection. Subarachnoid hemorrhage is the commonest major complication of cisternal puncture, with at least 30 reported fatalities. Other serious complications result from direct puncture of brain substance.Cisternal puncture is not an appropriate alternative to a difficult lumbar puncture, and indications for its use are limited. The occasional required cisternal tap should be performed only by persons carefully trained in the technique, preferably utilizing fluoroscopic guidance, and only where neurosurgical assistance is readily available.Post-puncture subarachnoid hemorrhage accompanied by progressive obtundation requires emergency evaluation and consideration of posterior fossa decompression.

Topics: Adult; Amphotericin B; Brain Stem; Cisterna Magna; Coccidioidomycosis; Female; Humans; Infarction; Injections, Spinal; Male; Meningitis; Middle Aged; Punctures; Subarachnoid Hemorrhage

Topics: Amphotericin B; California; Coccidioides; Coccidioidomycosis; Disease Outbreaks; Humans; Injections, Spinal; Meningitis; Occupational Diseases; Soil Microbiology

The localization of coccidioidal meningitis in the basilar regions, with resultant hydrocephalus and uniformly fatal outcome, has necessitated intrathecal injection of amphotericin B via cisternal puncture or subcutaneous ventricular reservoir for successful therapy. A simpler form of treatment is described here, whereby amphotericin B diluted in 10 percent glucose solution is injected via lumbar puncture, and delivered to the base of the skull by tilting the patient to a head-down position. A simultaneously performed hyperbaric cisternogram with (131)I-serum albumin has demonstrated satisfactory migration of the injected bolus to the occiput. This method of administration resulted in successful suppressive treatment of one patient, including two years of follow-up without serious sequelae or relapse.

Topics: Aged; Amphotericin B; Coccidioidomycosis; Humans; Injections, Spinal; Male; Meningitis; Methods

Topics: Adult; Amphotericin B; Cryptococcus; Humans; Male; Meningitis

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; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Female; Humans; Lung Diseases, Fungal; Meningitis; Natamycin; Tuberculosis, Meningeal

Topics: Adolescent; Adult; Aged; Amphotericin B; Candida albicans; Candidiasis; Child; Child, Preschool; Endocarditis; Esophagitis; Female; Humans; Laryngitis; Male; Meningitis; Middle Aged; Pneumonia; Stomatitis; Vaginitis

Topics: Amphotericin B; Arthritis; Candida albicans; Candidiasis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Joint Diseases; Meconium; Meningitis; Periostitis; Radiography

Topics: Amphotericin B; Anemia; Blood Transfusion; Blood Urea Nitrogen; Candida albicans; Candidiasis; Female; Humans; Infant; Iron; Leg Ulcer; Leukocyte Count; Meningitis; Uremia

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: Adolescent; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Female; Flucytosine; Humans; Meningitis; Pregnancy; Pregnancy Complications, Infectious

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia; Child; Endocarditis; Female; Histoplasma; Histoplasmosis; Humans; Infant; Larynx; Liver; Male; Meningitis; Middle Aged; Mouth; Prospective Studies; Thrombocytopenia; Urine

Topics: Amphotericin B; Cryptococcosis; Female; Humans; Lupus Erythematosus, Systemic; Meningitis; Methylprednisolone; Middle Aged

Topics: Amphotericin B; Arthritis, Infectious; Candidiasis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intra-Articular; Injections, Intravenous; Injections, Spinal; Meningitis; Pregnancy

Topics: Amphotericin B; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Candidiasis, Cutaneous; Cryptococcosis; Female; Humans; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Kidney Diseases; Meningitis

Topics: Adolescent; Amphotericin B; Calcium; Chlorides; Creatine Kinase; Female; Humans; Hypokalemia; Meningitis; Muscular Diseases; Potassium

Topics: Adult; Amphotericin B; Canada; Cerebral Ventriculography; Chronic Disease; Coccidioidomycosis; Humans; Hydrocephalus; Male; Meningitis; Microscopy, Electron; South America; Time Factors; United States

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: Amphotericin B; Cryptococcosis; Humans; Meningitis

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; Biopsy; Cryptococcosis; Humans; Lung Diseases, Fungal; Male; Meningitis; Meningococcal Infections; Radiography

Topics: Adolescent; Adult; Amphotericin B; Coccidioides; Coccidioidomycosis; Complement Fixation Tests; Female; Humans; Male; Meningitis; Neurologic Manifestations; Skin Tests

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

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Humans; Imidazoles; Infant, Newborn; Infant, Premature, Diseases; Meningitis

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: Adult; Amphotericin B; Cryptococcosis; Humans; Hypokalemia; Kidney; Kidney Concentrating Ability; Male; Meningitis; Muscular Diseases; Myoglobinuria; Potassium; Potassium Chloride

Topics: Adult; Amphotericin B; Bacteriological Techniques; Biopsy; Brain Abscess; Cerebrospinal Fluid Proteins; Hemiplegia; Humans; Isoniazid; Joint Diseases; Lung Diseases; Male; Meningitis; Nocardia Infections; Polymyxins; Prednisone; Pseudomonas Infections; Sarcoidosis; Skin Diseases; Sporotrichosis; Tetracycline

Topics: Age Factors; Amphotericin B; Anti-Bacterial Agents; Cryptococcus; Escherichia coli Infections; Humans; Injections, Intravenous; Injections, Spinal; Intracranial Pressure; Leptospira; Meningitis; Meningitis, Haemophilus; Meningitis, Listeria; Meningitis, Meningococcal; Meningitis, Pneumococcal; Meningitis, Viral; Microbial Sensitivity Tests; Penicillins; Staphylococcal Infections; Streptococcal Infections; Streptomycin; Sulfonamides; Tuberculosis, Meningeal

Topics: Amphotericin B; Child; Cryptococcosis; Female; Humans; Leukemia, Lymphoid; Leukocyte Count; Meningitis

Topics: Adult; Amphotericin B; Brain; Cryptococcosis; Diagnosis, Differential; Heart Diseases; Humans; Lung; Male; Meningitis; Nephrocalcinosis; Prednisolone; Sarcoidosis; Sepsis

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: Adult; Amphotericin B; Child; Cryptococcosis; Cytosine; Female; Humans; Meningitis

Topics: Acremonium; Adult; Amphotericin B; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Mycoses

Topics: Amphotericin B; Arachnoiditis; Biological Transport; Blood Glucose; Blood-Brain Barrier; Cryptococcosis; Glucose; Humans; Meningitis; Models, Biological

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

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; 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

Topics: Adolescent; Amphotericin B; Cerebrospinal Fluid; Cerebrovascular Circulation; Coccidioides; Female; Humans; Meningitis; Mycoses; Radionuclide Imaging; Serum Albumin, Radio-Iodinated; Technetium

Topics: Adolescent; Adult; Amphotericin B; Brain Abscess; Brain Neoplasms; Cerebral Ventriculography; Chronic Disease; Coccidioidomycosis; Complement Fixation Tests; Diagnosis, Differential; Female; Humans; Male; Meningitis; Skin Tests

Topics: Adult; Aged; Amphotericin B; British Columbia; Cryptococcosis; Female; Humans; Male; Meningitis

Topics: Amphotericin B; Bronchopneumonia; Candidiasis; Child; Colistin; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infusions, Parenteral; Male; Meningitis; Sepsis; Sterilization; Vaccination

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: 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: Amphotericin B; Humans; Meningitis; Mycoses

Topics: Amphotericin B; Cisterna Magna; Cryptococcosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Middle Aged

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: Amphotericin B; Candida; Candidiasis; Humans; Infant; Male; Meningitis

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: Adrenal Cortex Hormones; Amphotericin B; Anti-Bacterial Agents; Antitubercular Agents; Ethionamide; Humans; Isoniazid; Meningitis; Meningitis, Viral; Mycoses; Prognosis; Sarcoidosis; Streptodornase and Streptokinase; Streptomycin; Syphilis; Tuberculosis, Meningeal

Topics: Amphotericin B; Cerebrospinal Fluid; Fluorescent Antibody Technique; Humans; Male; Meningitis; Middle Aged; Sporotrichosis

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Cerebrospinal Fluid; Female; Humans; Meningitis

Topics: Adult; Amphotericin B; Blastomycosis; Female; Humans; Injections, Intravenous; Injections, Spinal; Meningitis; Radiography, Thoracic

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

Topics: Amphotericin B; Cryptococcus; Humans; Meningitis; Meningitis, Cryptococcal

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Drug Therapy; Humans; Meningitis

Topics: Adult; Amphotericin B; Antibody Formation; Cryptococcosis; Humans; Meningitis; Myasthenia Gravis; Thymoma

Topics: Amphotericin B; Candidiasis; Craniotomy; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Infusions, Parenteral; Meningitis; Pregnancy

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: Adenoidectomy; Amphotericin B; Anemia; Anti-Bacterial Agents; Ear, Inner; Hemorrhage; Hydrocarbons; Meningitis; Mycoses; Nystatin; Otitis Media; Otolaryngology; Pediatrics; Pharynx; Streptomycin; Tonsillectomy; Toxicology; Vitamins

Topics: Abscess; Amphotericin B; Brain Abscess; Candidiasis; Carrier State; Child; Chloramphenicol; Colistin; Deoxyribonucleases; DNA; Empyema; Enteritis; Humans; Kanamycin; Meningitis; Methicillin; Penicillins; Peritonitis; Phlebitis; Pneumonia; Pneumothorax; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Sulfadiazine; Troleandomycin

Topics: Amphotericin B; Biological Phenomena; Candida albicans; Candidiasis; Humans; Infant; Meningitis; Physiological Phenomena

Topics: Amphotericin B; Bone Diseases; Cervical Vertebrae; Coccidioides; Coccidioidomycosis; Humans; Meningitis; Paralysis; Quadriplegia; Radiography; Surgical Procedures, Operative

In a study of 25 patients the usefulness of amphotericin B in the control of meningeal infection produced by Coccidioides immitis was established. Initial treatment must be intensive, consisting of intravenous and intraspinally administered amphotericin B. Serologic evaluation of coccidioidal disease provides the most important single criterion for determining the course of the meningeal infection and for estimating the response of the patient to amphotericin B therapy. Final control of coccidioidal meningitis rests upon the prevention of relapse after completion of initial intensive therapy. This requires continued suppressive fungistasis by regular intracisternal injections of amphotericin B at intervals of three to seven days after the patient returns home. Such suppressive cisternal therapy does not replace the initial intensive use of both intravenously and intraspinally administered amphotericin B. This "local" type of inhibition of C. immitis is without toxic effect upon the kidney, the red blood cells or the serum potassium values which may be associated with the intravenous administration of amphotericin B. Such intraspinal therapy, by lowering the total intravenous dosage required in the initial phase of treatment, results in a proportionate decrease in the degree of nephrotoxicity produced by amphotericin B. The total intravenous dosage given ordinarily should not exceed 5 grams. The long-term therapeutic plan as outlined permits the development of an adequate immune mechanism that appears essential to complete recovery from coccidioidal meningitis. The importance of such immunity in the recovery process has been previously indicated and confirmed by detailed study of a patient who required immunosuppression for successful homotransplantation of a kidney.

Topics: Administration, Intravenous; Adolescent; Amphotericin B; Black People; Cerebrospinal Fluid; Child; Cisterna Magna; Coccidioides; Coccidioidomycosis; Complement Fixation Tests; Dactinomycin; Dosage Forms; Humans; Imidazoles; Immunity; Infusions, Intravenous; Injections; Injections, Intravenous; Injections, Spinal; Kidney Transplantation; Meningitis; Meningitis, Fungal; Purines; Subarachnoid Space; Toxicology; Transplantation Immunology; White People

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; Anaphylaxis; Anemia; Anuria; Blushing; Feeding and Eating Disorders; Fever; Headache; Heart Failure; Humans; Hypokalemia; Kidney Diseases; Liver Diseases; Meningitis; Nausea; Pain; Paralysis; Paresthesia; Phlebitis; Seizures; Thrombocytopenia; Toxicology; Ventricular Fibrillation; Vertigo; Vomiting

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; 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; Cryptococcus; Humans; Meningitis; Meningitis, Cryptococcal; Prognosis

Topics: Amphotericin B; Candida; Candidiasis; Humans; Meningitis; Meningitis, Fungal

Topics: Amphotericin B; Cryptococcosis; Humans; Injections, Intraventricular; Lung Diseases; Lung Diseases, Fungal; Meningitis; Pathology; Radiography, Thoracic

Topics: Amphotericin B; Anti-Bacterial Agents; Cerebrospinal Fluid; Chloramphenicol; Humans; Influenza, Human; Leptospirosis; Meningitis; Meningitis, Pneumococcal; Meningitis, Viral; Mycoses; Neurosyphilis; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcus pneumoniae; Streptomycin; Tuberculosis; Tuberculosis, Meningeal

Topics: Alopecia; Amphotericin B; Candida tropicalis; Candidiasis; Child; Haemophilus; Humans; Kidney Diseases; Liver Diseases; Meningitis; Meningitis, Haemophilus; Sepsis

Topics: Amphotericin B; Cerebrospinal Fluid; Geriatrics; Histoplasma; Histoplasmosis; Humans; Meningitis

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fungicides, Industrial; Meningitis; Meningitis, Cryptococcal; Pregnancy; Pregnancy Complications

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fungicides, Industrial; Humans; Meningitis; Meningitis, Cryptococcal

Topics: Amphotericin B; Candida; Candidiasis; Hodgkin Disease; Humans; Meningitis

Topics: Amphotericin B; Coccidioidomycosis; Humans; Meningitis

Amphotericin B is the first agent to alter favorably the course of coccidioidal meningitis. The morbidity and toxicity of the drug are at present its chief limiting factors. Although no cures were obtained in a series of 11 cases, significant remissions usually followed a course of therapy. Comparison with similar groups showed a significant prolongation of life in adequately treated cases.

Topics: Amphotericin B; Antifungal Agents; Coccidioidomycosis; Fungicides, Industrial; Humans; Life; Meningitis; Meningitis, Fungal

Topics: Amphotericin B; Antifungal Agents; Child; Fungicides, Industrial; Histoplasma; Histoplasmosis; Humans; Infant; Medical Records; Meningitis; Physiological Phenomena

Topics: Amphotericin B; Antifungal Agents; Child; Cryptococcosis; Cryptococcus; Infant; Meningitis

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Meningitis

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fungicides, Industrial; Humans; Meningitis; Meningitis, Cryptococcal

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

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Humans; Medical Records; Meningitis

Topics: Amphotericin B; Antifungal Agents; Coccidioidomycosis; Fungicides, Industrial; Humans; Meningitis; Meningitis, Fungal

Topics: Amphotericin B; Cryptococcosis; Cryptococcus; Meningitis

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

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fungicides, Industrial; Humans; Meningitis; Meningitis, Cryptococcal

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Heart Arrest; Meningitis