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2021 JUL 3 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on Drugs and Therapies - Antifungals have been presented. According [...]

2021 MAR 13 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]

Background: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting. Objective: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. Design: An open randomized, controlled, multicenter trial, powered for equivalence. Setting: 60 oncology centers in 10 countries. Patients: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. Intervention: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution. Measurements: Defervescence, breakthrough fungal infection, drug-related adverse events, and death. Results: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P=0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P=0.001). Significantly more amphotericin B recipients had nephrotoxicity (P Conclusions: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Background: Visceral leishmaniasis (kala-azar) is a worldwide, disseminated intracellular protozoa! infection for which prolonged, conventional therapy with pentavalent antimony has become increasingly less effective. Objective: To determine the efficacy and minimal effective dose of short-course therapy with amphotericin B lipid complex in visceral leishmaniasis. Design: A randomized, open-label study. Setting: Inpatient kala-azar treatment unit in the state of Bihar in northeast India, where visceral leishmaniasis is endemic. Patients: 60 patients with active infection who had not responded to or who had relapse after receiving conventional ([is greater than] 30 days) treatment with pentavalent antimony. Intervention: Intravenous amphotericin B lipid complex was given once daily for 5 consecutive days by 2-hour infusion. Patients were randomly assigned to receive 1, 2, or 3 mg/kg of body weight per day (total doses of 5,10, or 15 mg/kg, respectively). Measurements: Clinical and parasitologic responses (the latter were measured by parasite density score of the splenic aspirate) were determined 14 days after treatment. Definitive responses were assessed 6 months after treatment according to clinical outcomes and findings on examination of bone marrow aspirate. Results: All 60 patients responded to 5 days of treatment. Fourteen days after therapy, all patients had parasite-free splenic aspirates and were considered to have an apparent clinical and parasitologic response. Six months after therapy, definitive responses were documented in 16 of 19 (84% [95% CI, 60% to 97%]), 18 of 20 (90% [CI, 68% to 99%]), and 21 of 21 (100% [CI, 84% to 100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively. Conclusion: Short-course therapy with low-dose amphotericin B lipid complex is effective for visceral leishmaniasis and is an important therapeutic alternative in the management of this serious intracellular protozoal infection., Visceral leishmaniasis seems completely responsive to low-dose short-term treatment with amphotericin B lipid complex. This protozoal infection, also known as black fever or kala-azar, has become less responsive to the traditional treatment using antimony. Intravenous amphotericin B was given in three different dosages to 60 patients for 5 days. After 14 days, all were considered free of parasites. A small percentage of patients taking the lower dose had a relapse, but re-treatment with a higher dose was confirmed successful after a 6-month follow-up.

PURPOSE: To compare the efficacy and toxicity of fluconazole and amphotericin B in the treatment of hematogenous candidiasis in cancer patients. PATIENTS AND METHODS: A matched cohort study of cancer patients with hematogenous candidiasis was conducted. Forty-five patients with hematogenous candidiasis who received fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992 were matched to 45 patients treated with amphotericin B 10.3 to 1.2 mg/kg/day) for the same diagnosis. Criteria for matching included the following prognostic variables at the initiation of therapy: pneumonia, neutropenia (

Invasive fungal infections have become a major source of morbidity and mortality in the modern surgical intensive care unit. PatienTs at risk for invasion and dissemination are common, and are not as ill as thought previously. Severity of ilLness (APACHE II score >10, ventilator use for >48 hours), antibiotics, central venous lines, total parenteral nutrition, burns, and immunosuppression are the most common risk. factors. Recognition of these risk factors should arouse a high index of suspicion for the diagnosis of invasion or dissemination. Unfortunately, laboratory tests alone lack sensitivity and specificity. Therefore, the diagnosis of invasion and dissemination in the majority of cases requires the acquisition and proper interpretation of clinical evidence. Once the diagnosis is made, early systemic treatment is warranted. Reported toxicity and efficacy supports the use of fluconazole for most patients with invasive fungal infections. However, for the most critically ill patient amphotericin B remains the treatment of choice. Am J Surg. 1996;171:374-382.

Invasive fungal infections are more commonly identified in various categories of patients, mainly in cancer patients but also in those undergoing organ transplantation, patients in intensive care units, and those with AIDS. There is a great need to increase the awareness of practitioners who are still underestimating the morbidity and mortality relating to invasive fungal infections, and to stress the economic burden for the society and healthcare systems of invasive fungal infections. The list of fungal pathogens causing life-threatening complications has also increased recently, with the emergence of unusual fungi being more frequently identified in such settings. Early diagnosis of invasive fungal infections is still a major challenge for the clinician at the bedside. Identification of state-of-the-art management is also a difficult task for the clinical scientists involved in the assessment of optimal strategies to prevent and to treat those invasive fungal infections, although major progress has occurred in the last 5 years with the development of new, safe, and effective antifungal agents. Empiric therapy remains a very controversial issue that should be further investigated in high-quality clinical trials. Overall, clinical research in this difficult field requires independent and objective analysis; only large multi-center clinical trials can address these critical issues and rapidly provide convincing results leading to a better prognosis of patients with invasive fungal infections. These complications still represent too often an obstacle to successful control of severe underlying diseases. Clinical research on the appropriate ways to target fungi will not only define state-of-the-art management but also identify ineffective or redundant treatments. Such an approach will make a substantial contribution to the care of the high-risk patients within the next decade and will preserve our capacity for medical excellence.

Background: invasive fungal infections in the immunocompromised patient are associated with substantial mortality. The use of conventional amphotericin B, the mainstay of treatment, has often been limited by its adverse effects. The incorporation of amphotericin B into liposomes enables more drug to be given without an increase in adverse reactions. We examined the efficacy of AmBisome (Vestar Inc, San Diego, Calif), a small unilamellar liposomal formulation of amphotericin B, in the treatment of mycologically proven systemic fungal diseases. Methods: A retrospective analysis of the 'Compassionate Use of AmBisome' in 58 patients who were treated in 34 centers throughout the United Kingdom between July 1990 and August 1992, before licensure of the drug. Results: Thirty patients had a definite or probable mycologic diagnosis, including 17 who had invasive aspergillosis, nine with Candida infections (three with mucosal disease only), three with zygomycosis, and one with cryptococcal meningitis. The overall response rate was 59% for patients with aspergillosis (80% for those who had had no prior therapy with amphotericin B) and 56% for those with candidosis. More than 40% of those in whom AmBisome was used as 'salvage therapy' responded. A daily dose of up to 5 mg/kg was tolerated with minimal side effects. Conclusions: AmBisome is efficacious in the treatment of invasive fungal infections and provides an alternative therapy for those who fail to respond or become intolerant to conventional amphotericin B therapy. Arch Intern Med. 1995;155:1093-1098)

* Objective: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia. * Design: A randomized, controlled, multicenter trial. * Setting: 30 hematologic units in tertiary care or university hospitals. * Patients: 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia. * Intervention: Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours. * Measurements: An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B. * Results: Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 1 0% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). * Conclusion: Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated., Oral doses of amphotericin B and fluconazole seem to be equally effective in preventing fungal infections in adult patients with leukemia. Fluconazole tends to cause fewer severe side effects. Eight-hundred-twenty adults whose leukemia treatment had reduced the number of neutrophils, a white blood cell, were randomly assigned to receive one medication or the other. Systemic fungal infection occurred in 2.6% of the 420 taking fluconazole and 2.5% of the 400 taking amphotericin B. Superficial fungal infections occurred in 1.7% versus 2.7%, respectively. Nausea and vomiting occurred in 7% of those taking amphotericin B, and 3% had to discontinue treatment. They occurred in only 0.7% of the fluconazole patients, and no one had to discontinue treatment.

Background. Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as anti-fungal prophylaxis. Methods. Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity. Results. Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02). Conclusions. At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Blastomycosis is a disease that is caused by infection with a fungus known as Blastomyces dermatitides. This fungus has been found in soil in the United States, Canada, and Africa. It can cause lung and skin infections, and in severe cases it can infect the central nervous system (CNS) and result in lung failure (adult respiratory distress syndrome). Amphotericin B is used to treat patients who have more severe forms of the disease. Ketoconazole (KTZ) is an antifungal drug that is used to treat patients with mild to moderate blastomycosis. Treatment with high doses of KTZ can be toxic to the stomach and intestines. However, lower doses are associated with increased rates of relapse and drug failure. At the present time there is no way to identify the patients who will respond favorably to KTZ treatment. It has been reported that patients with genital and urinary tract involvement are more prone to relapse. This article describes the cases of two patients with blastomycosis who were treated with KTZ. When treatment was initiated, both patients had skin and lung infections, but did not have symptoms of CNS blastomycosis. KTZ treatment cured the lung and skin infections. However, in both cases infection spread to the CNS. Treatment with amphotericin B cured the CNS infections. It is suggested that all patients with disseminated blastomycosis be tested (by computed tomography or lumbar puncture) for CNS infection even if they do not have any CNS symptoms. (Consumer Summary produced by Reliance Medical Information, Inc.)

PURPOSE. To retrospectively study the prophylaxis of invasive asperginosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODs: Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS. Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal Invasive aspergillosis was suspected in a further 16 mm and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying with subsequent return of normal marrow function and resOlutiOn Of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION: intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration., Aspergillosis is an infection of bodily tissues or mucous membranes with the fungal species Aspergillus. It commonly occurs in patients who have depressed immune systems, such as cancer patients or those that have had organ transplants. A major risk for so-called opportunistic infections is neutropenia, a depletion of neutrophils (a type of immune cell) that often occurs in these patients. This study examined the records of patients with neutropenia for proven or suspected infection with Aspergillus from January 1977 to December 1988. The hospital unit and the air in it were examined for reservoirs of Aspergillus spores. The various prevention and treatment methods used during this time period were compared to see which ones were effective. During the period studied, 158 episodes requiring intensive treatment (including bone marrow transplant) for leukemia, lymphoma, or aplastic anemia occurred in 130 patients. Aspergillus infection did not occur in 89 (56.3 percent) of the episodes and colonies were detected in 31 (19.6 percent) of the episodes, but no clinical symptoms occurred. Suspected infection occurred in 16 patients (10.1 percent), all of whom were successfully treated with amphotericin B nasal spray, introduced as a treatment in 1985. Infection was definite in 22 patients (13.9 percent) and 12 of these patients died from the infection. Death from infection was highly correlated to whether or not the underlying disease entered remission at some point. The incidence of proven Aspergillus infection greatly decreased after nasal amphotericin B was introduced. Examinations in the hospital unit found spores present in each month examined. These results indicate that amphotericin B is very effective in preventing invasive aspergillosis in neutropenic patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer patients are susceptible to serious bacterial and fungal infections due to their impaired immunity, which is caused both by their disease and its treatment, both of which can decrease the number of white blood cells available to fight infection. Patients who experience a significant drop in the number of one subpopulation of white blood cells known as granulocytes are known as granulocytopenic, and when these patients develop fever, they are typically placed on several potent antibiotics. When those fevers persist, antifungal agents are often added. The most commonly used antifungal is amphotericin B, which is often effective but which carries a very high risk of damaging the liver and kidney. A study was performed in which 32 granulocytopenic cancer patients were given oral ketoconazole, another antifungal agent, and a total of 52 patients were given amphotericin B intravenously, for presumed fungal infections, after failing to respond to antibacterial agents. A total of 10 patients were later documented to have definite fungal infections. All five who were proven to have the fungus Aspergillus died, three on amphotericin B and two on ketoconazole. The five who had been infected with a species of Candida consisted of three initially on ketoconazole, who responded when switched to amphotericin B, and two initially on amphotericin B who responded to that therapy. Some explanations as to why ketoconazole proved to be inadequate to treat presumed or documented fungal infections in these cancer patients include the fact that the drug merely inhibits growth of the fungi, rather than killing them, as does amphotericin B. Ketoconazole is taken orally, and thus its absorption and subsequent levels in the bloodstream are susceptible to disturbances in the gut, whereas amphotericin B is give intravenously, and impervious to influences by the gut. Finally, ketoconazole is inactive against a number of fungal species, whereas amphotericin B has a broader spectrum of potency. Thus, while the toxic effects are great, until a better agent is developed, amphotericin B must remain the drug of choice for granulocytic cancer patients with presumed or documented fungal infections. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cryptococcal meningitis is an infection that occurs in approximately 10 percent of patients with acquired immunodeficiency syndrome (AIDS). It is a serious infection and results in death in nearly 60 percent of these patients. Amphotericin B and flucytosine are antifungal agents that can be used either alone or in combination to treat cryptococcal meningitis. A new antifungal agent, fluconazole, was evaluated for the treatment of infections caused by the fungus Cryptococcus neoformans. Fluconazole was compared with the combination antifungal regimen of amphotericin B and flucytosine. Fourteen patients received fluconazole, while the remainder received the combination therapy. Conversion of blood, urine, and cerebrospinal fluid cultures from positive to negative was the anticipated indication of successful treatment. Success was slower in patients receiving fluconazole than among those receiving amphotericin B. In seven of nine patients treated with fluconazole, cerebrospinal fluid cultures did not convert to negative. Overall, patients with less severe disease responded better to therapy. Fluconazole was well tolerated, while amphotericin B therapy was associated with nausea, vomiting, and chills, side effects commonly experienced with use of this drug. The investigators did not expect fluconazole to result in treatment failure. Although this drug has some effectiveness against cryptococci, higher doses may be required or it may need to be combined with flucytosine. An alternate regimen may be an initial short course of treatment with the successful combination of amphotericin B and flucytosine followed by treatment with fluconazole. This study did not establish fluconazole as an effective, nontoxic alternative to other antifungals. (Consumer Summary produced by Reliance Medical Information, Inc.)

ABSTRACT & COMMENTARY Synopsis: Caspofungin was superior to amphotericin B deoxycholate in the treatment of patients with invasive candidiasis. Source: Mora-Duarte J, et al. Comparison of caspofungin and amphotericin B [...]

Rhinocerebral mucormycosis with intracranial involvement has a high mortality. The standard therapy consists of aggressive surgical debridement accompanied by high doses of amphotericin B deoxycholate. Even with this therapy, the mortality rate has been 48% in the series reported since 1980. We treated a 60-year-old diabetic woman with rhinocerebral mucormycosis involving the cavernous sinus whose infection responded to medical therapy with amphotericin B lipid complex. To our knowledge, this is the only well-documented medical cure of a patient with rhinocerebral mucormycosis and intracranial involvement. (Arch Intern Med. 1996;156:337-339)

The new antifungal agent fluconazole was approved by the Food and Drug Administration (FDA) earlier this year. In humans, it is indicated for the treatment of fungal infections due to cryptococcal and candida fungi, while experience in animals demonstrated it to be effective for coccidioidomycosis, histoplasmosis, blastomycosis, and aspergillosis. An article in the August 1, 1990 issue of Annals of Internal Medicine describes a comparative study of fluconazole versus the combination of amphotericin B and flucytosine for the treatment of cryptococcal meningitis. Investigators hoped that this drug would be a useful replacement for other, more toxic antifungal agents, since initial reports of patients with acquired immunodeficiency syndrome (AIDS) were very encouraging. Conversion of cerebrospinal cultures was lower in patients who received fluconazole than among those given the combination treatment, and a higher death rate occurred. Aggressive therapy with amphotericin B and flucytosine is the preferred treatment regimen. Nevertheless, patients with cryptococcal meningitis and AIDS will require maintenance antifungal therapy and fluconazole may be useful for that purpose. Fluconazole may also be used for oral candida (thrush) infections in AIDS patients or patients receiving chemotherapy. Continued study of this new drug is needed to determine its effectiveness for the treatment of invasive systemic fungal diseases. (Consumer Summary produced by Reliance Medical Information, Inc.)

Byline: S. Sanath, N. Gogtay, N. Kshirsagar Background : In May 2003, an indigenously developed liposomal amphotericin B (FungisomeTM) was introduced in the Indian market for the treatment of systemic [...]

Patients with vaginitis due to highly azole resistant Candida glabrata can be particularly difficult to treat. We describe three cases of longstanding vaginal candidiasis due to C glabrata. These had [...]

Introduction: Fungal infections occur frequently in lung transplant patients, with the highest risk being in the early postoperative period (the initial hospitalization after lung transplantation). Aspergillus is responsible for more [...]

PURPOSE: Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated. PATIENTS AND METHODS: We randomly assigned 106 patients with absolute neutropenia ([is less than or equal to] 500 cells/al.) and persistent fever of undetermined origin ([is greater than] 38 [degrees] C) despite 1 week of broadspectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection. RESULTS: Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia. CONCLUSIONS: These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Am J Med. 1998;105:478-483. [C] 1998 by Excerpta Medica, Inc.

Male patients with AIDS (acquired immunodeficiency syndrome) who have been effectively treated for meningitis caused by the fungus Cryptococcus neoformans, can develop a persistent infection of the prostate gland by the fungus, without any immediate clinical symptoms. This occurred in 9 out of 41 (29 percent) patients with meningitis caused by C. neoformans. The fungus was detected in urine specimens of the patients and in prostate secretions in four of the patients. Three patients who were treated with amphotericin B, one of the drugs used in the original treatment regimen for the meningitis, had persistent infection but it did not become systemic. Six of the patients were treated with fluconazole, another drug that was used to treat the original meningitis; four of those patients no longer have the infection and two suffered a relapse, which was systemic. The presence of C. neoformans in the urine after adequate treatment for meningitis indicates that the fungus can sequester in the urinary tract, probably in the prostate gland. Infection of the prostate gland is often difficult to treat, since many drugs do not reach high enough levels in the prostate gland to be effective. The fungi can cause a systemic relapse that can affect the central nervous system, making the infection very serious. The use of alternatives to fluconazole, which did not inhibit systemic infections in a proportion of the patients, and longer treatment with amphotericin B, which did not allow systemic infections but was not effective in eradicating the urinary tract infection, are being investigated. (Consumer Summary produced by Reliance Medical Information, Inc.)

Chemotherapy usually reduces the ability of the immune system to fight infection. Patients receiving chemotherapy for the treatment of cancer are at risk for developing fungal infections, particularly candida albicans, because of their compromised immune system. Candida infections constitute 70 to 80 percent of all fungal infections in these patients. Invasive candida infections are difficult to diagnose. Patients having fever, which does not resolve after a course of antibiotics, are given the antifungal agent amphotericin B. Improvement in the patient's condition usually indicates that a fungus was the infective agent. Immunocompromised patients are unable to produce antibodies in response to candida albicans exposure. Therefore, blood tests which measure candida antibodies are not reliable. The diagnostic accuracy of a new test for candida detection, Cand-Tec, was evaluated. The test was performed on 142 patients receiving chemotherapy and radiation therapy. The sensitivity of the test was low; Cand-Tec was unable to provide a definitive diagnosis of invasive candida infection. Although this test could detect candida infection in the blood, it was not useful for detecting candida infection in the esophagus. The use of Cand-Tec did not increase early diagnosis of invasive candida infections which are currently detected by blood culture, tissue biopsy or after autopsy. Therefore, the current method of trial-and-error treatment with amphotericin B should be continued until better detection methods become available. (Consumer Summary produced by Reliance Medical Information, Inc.)

Fungal infections are relatively common, and are endemic in certain areas of the United States, such as California. Diseases such as coccidioidomycosis, blastomycosis and histoplasmosis were recognized early in this century, but only became well understood in the 1950s. Interest in these diseases as life-threatening illnesses increased with the use of aggressive cancer chemotherapy and steroids, which reduce the number of white blood cells and thus the ability of the body to protect itself from fungal infection. In patients with acute leukemia, the number of fungal infections occurring from 1978 to 1982 was 20 percent of all infections, as compared with 11 percent reported for 1966 to 1972 - perhaps as the result of such aggressive treatment. Standard practice has been to treat these patients with amphotericin B. Although generally effective, the drug has a number of side effects, including fever, chills, hypotension, and anemia. In laboratory animals a preparation of amphotericin B in combination with liposomes, cellular products that contain phospholipid, was found to reduce the drug's toxicity while increasing its effectiveness. The use of liposomal amphotericin B was studied in 46 patients who had various systemic fungal infections, 40 of whom had failed to respond to conventional amphotericin B therapy, and the other six of whom experienced toxic side effects from conventional treatment. Twenty-four of these patients had a complete response to this form of treatment while 22 patients showed no improvement. No long-term toxic effects were recorded, but the patients did experience acute short-term side effects, including fever, chills, and body fluid electrolyte imbalances. Confirming the results of animal experiments, lipososomal amphotericin B therapy was found to be both efficacious and to produce less severe side effects compared with conventional amphotericin B treatment.

Sarcoidosis is a disease of unknown cause which affects many body systems. It is characterized by a distinctive type of lesion, noncaseating granuloma. Eleven patients with sarcoidosis have now been found to be infected with the fungus Histoplasma capsulatum, the organism responsible for histoplasmosis. Fungal infections such as histoplasmosis are endemic in certain regions of the United States. In addition, other signs and symptoms are shared by sarcoidosis and histoplasmosis, such as enlarged lymph nodes within the chest, changes in blood chemistry marked by elevation in sedimentation rate, and the presence of noncaseating granulomas in some but not all histoplasmosis patients. It is hypothesized that sarcoidosis may be an unusual immune reaction to an underlying infection with Histoplasma capsulatum. Although treatment with the antifungal drug amphotericin B was unsuccessful, corticosteroids were effective. Prospective studies are required to determine the exact nature of the relationship between sarcoidosis and histoplasmosis. This study suggests that active histoplasmosis must be investigated in sarcoidosis patients who live in areas which are endemic for histoplasmosis.