amphotericin-b and Liver-Diseases

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Topics: Aged; Amphotericin B; Antifungal Agents; Autopsy; Fatal Outcome; Ferritins; Galactose; Humans; Invasive Fungal Infections; Liver Diseases; Male; Mannans; Mucormycosis; Primary Myelofibrosis; Spleen

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole-trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.

Topics: Adolescent; Adult; Amphotericin B; Female; Fungal Proteins; Humans; Hypertension, Portal; Latin America; Liver Diseases; Male; Paracoccidioides; Paracoccidioidomycosis; Phylogeny; Sequence Analysis, DNA; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy- and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. CASE REPORT We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. CONCLUSIONS Among patients with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy.

Topics: Amphotericin B; Antifungal Agents; Chemotherapy, Adjuvant; Fatal Outcome; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Liver Diseases; Middle Aged; Mucormycosis; Risk Factors; Treatment Failure; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antiprotozoal Agents; Humans; Immunosuppression Therapy; Leishmaniasis, Visceral; Liver Diseases; Liver Transplantation; Male; Middle Aged

Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Azoles; Candidiasis; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Therapy, Combination; Echinocandins; Fungemia; Hematologic Diseases; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Kidney Diseases; Liver Diseases; Mice; Neutropenia; Risk Factors

Empirical antifungal therapy has been shown to decrease the number of documented fungal infections in the setting of persistent fever during neutropenia. For decades, amphotericin B deoxycholate has been considered the agent of choice for first-line therapy in this setting. New antifungal agents associated with less toxicity, including the lipid formulations of amphotericin, voriconazole, and caspofungin, are now available and are considered to be suitable alternative first-line agents. In order to ensure appropriate therapy, however, the clinician must consider not only the differences between these antifungals but also patient-specific factors before initiating treatment.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Clinical Trials as Topic; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Echinocandins; Fever; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Liposomes; Liver Diseases; Mycoses; Neutropenia; Pyrimidines; Triazoles; Voriconazole

Amphotericin B reformulated into the liposomal formulation known as AmBisome (amphotericin B, hydrogenated soy phosphatidylcholine, cholesterol and dimyristoyl phosphatidylglycerol) can be safely administered at dosages 15 times higher than the conventional drug with the same broad spectrum of activity. Increased doses demonstrate non-linear clearance with saturation of the reticuloendothelial system (RES) and redistribution of the drug into non-RES tissues. The efficacy of this liposomal amphotericin B formulation appears to be related both to improved tissue penetration in the lungs, brain, kidneys, liver and spleen along with sustained bioactivity of therapeutic drug levels in these target tissues.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain Diseases; Dermatomycoses; Humans; Liver Diseases; Lung Diseases, Fungal; Mycoses; Splenic Diseases

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: Adult; Amphotericin B; Animals; Anti-Bacterial Agents; Bacitracin; Cats; Cycloserine; Drug Antagonism; Drug Hypersensitivity; Female; Hearing Disorders; Humans; Intestinal Diseases; Kidney Diseases; Liver Diseases; Male; Mental Disorders; Middle Aged; Neomycin; Novobiocin; Polymyxins; Stomach Diseases; Vision Disorders

The aim of this study was to evaluate the efficacy of two antifungal prophylaxis regimens in liver transplant recipients. One hundred and twenty-nine consecutive recipients were randomized to receive sequential treatment with intravenous liposomal amphotericin B + oral itraconazole, intravenous fluconazole + oral itraconazole, or intravenous and oral placebo. Frequency and incidence of mycotic colonization, local and systemic infection of mycotic origin, causes of death, and possible risk factors for mycotic infection were evaluated. The incidence of mycotic colonization was higher in the placebo group ( P<0.01), but there was no significant difference in the incidence of infection between the three groups. Pre-transplant colonization, severity of liver disease, and graft rejection were all risk factors for the development of fungal infection. The routine use of antifungal prophylaxis for all liver transplant recipients does not seem to be justified.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluconazole; Humans; Immunosuppressive Agents; Itraconazole; Liver Diseases; Liver Transplantation; Male; Middle Aged; Mycoses; Placebos; Postoperative Complications; Survival Analysis

The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C(ave)) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 microg h/ml, C(ave) was 0.50 +/- 0.11 microg/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 microg/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC with complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Combinations; Female; Humans; Liver Diseases; Male; Phosphatidylcholines; Phosphatidylglycerols; Splenic Diseases

To study the efficacy of fluconazole against chronic disseminated candidiasis (hepatosplenic candidiasis) in patients with leukemia in whom amphotericin B treatment had failed.. Retrospective analysis of patients with chronic disseminated candidiasis treated with fluconazole on a compassionate investigational new drug protocol.. Multi-institutional.. Twenty consecutive patients received 100 to 400 mg of fluconazole per day for a median of 30 weeks. All had either failed to respond to treatment with more than 2 g of amphotericin B or had serious amphotericin B-related toxicities.. Fourteen of 16 evaluable patients (88%) responded. Responses were observed in seven of nine patients in whom adequate doses of amphotericin B had failed and in all seven patients who had amphotericin B-related toxicities. In 12 patients, cytotoxic chemotherapy was continued without flare of the infection. Fluconazole was well tolerated with rare side effects. Aspergillus superinfection developed in three patients and contributed to the death of two of them.. Fluconazole is a safe and effective agent with significant activity against chronic disseminated candidiasis.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Child, Preschool; Chronic Disease; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Retrospective Studies; Splenic Diseases; Superinfection

Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000-400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region. This is the first report showing such extreme latency of VL in a European traveller. This case is furthermore unusual because it suggests primary treatment failure to liposomal amphotericin B.. An 80-year-old man who was on immunosuppressive treatment due to a non-specific inflammatory disease of the liver and kidney presented to our hospital with recurrent fever, fatigue and bloody diarrhoea. Histopathological analysis from a colon biopsy showed intracellular amastigotes. The diagnosis of VL was confirmed by polymerase-chain-reaction (PCR) of the colon biopsy. PCR was also performed in plasma, a bronchopulmonary lavage, a lymph node, liver and bone marrow biopsy and proved L. donovani as causative species. The disseminated infection was unresponsive to treatment with liposomal amphotericin B as recommended in immunosuppressed individuals despite stopping immunosuppressive treatment.. Imported cases of VL to non-endemic regions are increasing due to extensive international travel and migration. Furthermore, the increase of elderly patients and immunosuppressed individuals, secondary to HIV, post-transplant and chemotherapeutic agents, has resulted in an increase of VL also in endemic regions of Europe. It is thus important for physicians to be able to recognize the infection. This case also demonstrates treatment failure to amphotericin B, which was only a known problem in patients with HIV until now. The knowledge of this as a possible complication is important for specialists treating the disease.

Topics: Aged, 80 and over; Amphotericin B; Antiprotozoal Agents; Azathioprine; Biopsy; Colon; Europe; Humans; Immunocompromised Host; Immunosuppressive Agents; India; Indonesia; Kidney Diseases; Leishmaniasis, Visceral; Liver Diseases; Male; Polymerase Chain Reaction; Positron Emission Tomography Computed Tomography; Severity of Illness Index; Time Factors; Travel; Treatment Failure

Visceral leishmaniasis is a disease caused by the protozoan Leishmania sp. and is transmitted by Lutzomyia longipalpis (sand fly). In renal transplant recipients, visceral leishmaniasis causes severe damage to the liver, spleen, and hematopoietic system, as well as poor outcomes for patients with transplanted kidneys. This study describes the largest series of cases of visceral leishmaniasis in renal transplant recipients, providing important information about the diagnostic routines and therapeutic strategies in this patient population.. A retrospective, descriptive study was performed to analyze the distribution and evaluate the extent of the epidemiologic, clinical, diagnostic and therapeutic aspects of 30 renal transplant recipients from endemic regions who presented with visceral leishmaniasis in the post-transplantation period.. In this study, visceral leishmaniasis was more frequent in men (80%). The mean age of presentation was 40 ± 10.5 years. The majority of patients worked in urban areas (66.7%), cohabitated with domestic animals (90%), and were from low-income households. In 73.3% of cases, diagnosis was made by direct isolation of Leishmania forms. Patients were treated with liposomal amphotericin, resulting in a high degree of disease remission (80%).. This study describes the largest series of visceral leishmaniasis in renal transplant recipients and expands clinical-epidemiological knowledge for transplantation teams to perform adequate disease management for this specific patient population.

Topics: Adult; Age Distribution; Amphotericin B; Animals; Animals, Domestic; Antiprotozoal Agents; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Leishmania; Leishmaniasis, Visceral; Liver Diseases; Male; Middle Aged; Residence Characteristics; Retrospective Studies; Sex Distribution; Splenic Diseases; Transplant Recipients

The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Colloids; Critical Illness; Female; Humans; Liver Diseases; Male; Middle Aged; Young Adult

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a cumulative incidence of around 2% during the first year after SOT. The associated mortality rate is high, and surgical debridement is frequently required as part of the treatment along with antifungal therapy based mostly on amphotericin B formulations, We describe here an unusual case of hepatic mucormycosis in a liver transplant recipient that was successfully treated with clinical therapy based on liposomal amphotericin B followed by posaconazole, without surgical resection.

Topics: Amphotericin B; Antifungal Agents; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Liver Diseases; Liver Transplantation; Mucormycosis; Time Factors; Treatment Outcome; Triazoles; Young Adult

Antifungal prophylaxis in the haematological patient is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukaemias, myelodysplastic syndromes and autologous or allogenic hematopoietic stem cell transplantation. Over the years, different scientific societies have established a series of recommendations on antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each one of the agents must be personalised, adapted to the characteristics of each patient and to possible interactions with concomitant medication.

Topics: Algorithms; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Biological Availability; Decision Trees; Drug Interactions; Echinocandins; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Diseases; Mycoses; Myelodysplastic Syndromes; Postoperative Complications; Practice Guidelines as Topic; Premedication; Triazoles

Invasive fungal infection negatively influences the morbidity and mortality in heavily immuno-incompetent patients. Diagnosis of non-Aspergillus mould infections remains challenging despite application of a wide spectrum of non-culture-based microbiological techniques. Invasive diagnostic procedures are often essential. In this article, we present the case of a 15-month-old boy diagnosed with Rhizopus microsporus var. rhizopodiformis liver mycetoma during induction chemotherapy for acute promyelocytic leukaemia. Following surgery, he was effectively treated with a combination of ABLC and posaconazole during ongoing intensive chemotherapy. Posaconazole was also used as long-term secondary prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Humans; Infant; Leukemia, Myeloid, Acute; Liver; Liver Diseases; Male; Mycetoma; Rhizopus; Triazoles

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

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

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Appendicitis; Candidiasis; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Splenic Diseases

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Fatal Outcome; Humans; Immunocompromised Host; Liver Diseases; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography; Splenic Diseases; Typhlitis

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Dextrans; Disease Models, Animal; Drug Therapy, Combination; Granuloma; Liver Diseases; Male; Mice; Mice, Inbred C57BL

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Echinocandins; Female; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Liver Diseases; Peptides, Cyclic; Splenic Diseases

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Female; Humans; Itraconazole; Kidney Transplantation; Liver Diseases

A 14-year-old girl with leukemia had Doppler ultrasound evidence of hepatic necrosis, thought to be caused by a lipid formulation of amphotericin B, which has not been previously reported. It seems prudent to exert caution when retreating patients with previous hepatocellular damage with lipid formulations of amphotericin B.

Topics: Adolescent; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Cytarabine; Etoposide; Female; Humans; Idarubicin; Leukemia, Myeloid; Liposomes; Liver; Liver Diseases

A case of liver and brain mucormycosis in a 73-y-old diabetic patient is described. The patient presented with fever and a moderate, tender hepatomegaly and a C/T scan examination of the abdomen and brain showed multiple hepatic and cerebral nodular lesions. The largest of the liver lesions was aspirated and broad hyphae of mucor were demonstrated in the purulent material obtained. The patient was treated successfully (for 40 d) with intravenous liposomal amphotericin B and then with itraconazole for 3 months. To our knowledge, this is the first case of a diabetic patient with both liver and brain mucormycosis who has been treated successfully.

Topics: Aged; Amphotericin B; Antifungal Agents; Brain Diseases; Diabetes Mellitus, Type 2; Female; Humans; Liver Diseases; Mucormycosis; Opportunistic Infections

In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride-rich emulsion (AB-emulsion). The present paper compares the severity of the histopathological alterations as determined by morphometry produced in the target tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the conventional formulation AB-deoxycholate (DOC) following subacute AB treatment. No morphological alterations were seen in the spleen and heart following both AB-DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and lungs are basically the same for both formulations, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compared to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration. These three treatment regimens consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive days. Thus, these regimens consisted of total doses varying from 8-12 mg/kg of body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition, acute interstitial inflammation was observed in the lungs prior to interstitial and alveolar edema. The intensity of the histopathological damage increase with the dose and with the reduction in the time interval between AB administrations. Abnormal serum biochemical parameters were observed for serum urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decreased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effects induced by in vitro and in vivo tests with AB-emulsion treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Chemical and Drug Induced Liver Injury; Deoxycholic Acid; Fat Emulsions, Intravenous; Kidney; Kidney Diseases; Liver; Liver Diseases; Lung; Lung Diseases; Male; Myocardium; Rats; Rats, Wistar; Triglycerides

Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5.75 d (range 0-14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candidiasis; Female; Fever of Unknown Origin; Genes, Fungal; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization; Leukemia, Myeloid; Liver Diseases; Lung Diseases, Fungal; Male; Middle Aged; Monitoring, Physiologic; Neutropenia; Polymerase Chain Reaction; Sensitivity and Specificity

Chronic systemic (hepatosplenic) candidiasis (CSC) is a syndrome of invasive candidiasis characterized by fever without localizing signs or symptoms. It occurs predominantly in patients with acute leukemia, after prolonged severe neutropenia. We report a young woman who underwent extensive chemotherapy for granulocytic sarcoma of the ovary; CSC then developed in this patient. She was successfully treated with fluconazole and liposomal amphotericin B. Clinical presentation, diagnostic problems, and the current successful treatment with fluconazole and liposomal amphotericin B are discussed.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Chronic Disease; Female; Fluconazole; Humans; Liver Diseases; Opportunistic Infections; Ovarian Neoplasms; Sarcoma; Splenic Diseases; Tomography, X-Ray Computed

Hepatosplenic candidiasis following granulocytopenic periods is a relatively recently recognised problem in immunocompromised patients, particularly in those with acute leukaemia. We present three patients in whom diagnosis of hepatosplenic candidiasis was suspected on the basis of ultrasonographic (US), computed tomographic (CT) findings and confirmed by laparoscopy and biopsy of liver lesions. All three patients were successfully treated briefly with amphotericin B, followed by a longer period of fluconazole. In one patient laparotomy and surgical evacuation of abscesses was performed. This condition could be more often recognised by careful follow-up of liver function test, C-reactive protein level, ultrasonography, CT and MRI after recovery from chemotherapy-induced neutropenia.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Female; Fluconazole; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Neutropenia; Opportunistic Infections; Splenic Diseases

A retrospective study of 23 patients with acute leukaemia and hepatosplenic candidiasis (HSC) was conducted to evaluate clinical treatment characteristics in terms of amount and duration of antifungal agents and to assess treatment outcome. Patients were admitted to two major tertiary care centres between 1990 and 1998. The diagnosis of HSC was based on clinical, blood cultures, histologic and imaging studies. Patients were treated with amphotericin B without interruption of the planned chemotherapy regimens. Serial magnetic resonance imaging (MRI) studies were the main tool for following patients' response and activity of the fungal lesions in conjunction with clinical and laboratory parameters. Treatment with amphotericin B was continued until resolution of all clinical symptoms and signs attributable to HSC, obtaining negative blood cultures and the appearance of at least healed lesions on MRI. Amphotericin B was discontinued in four patients because of severe nephrotoxicity (two patients), or continuous fever and persistent fungal lesions on MRI (two patients). Amphotericin B lipid complex (ABELCET) was successfully used as salvage therapy for these refractory patients. Four patients died with evidence of HSC despite treatment and supportive measures. The response rate for treatment of HSC was 82%. The mean total dose of amphotericin B including empirical treatment was 4 g and the median duration of treatment for responding patients was 112 d. The median number of days of anti- fungal treatment before the disappearance of fever was 19 d. Our results confirmed the need for protracted courses of antifungal agents for the successful eradication of HSC. Chemotherapy for the underlying disorder should not be interrupted or delayed in order to treat HSC.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Fever; Humans; Leukemia, Myeloid; Liver Diseases; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Splenic Diseases

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candidiasis; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Humans; Leukemia, Myeloid; Liver Diseases; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Splenic Diseases

A case of isolated localized hepatic mucormycosis in an immunocompetent 3 1/2-yr-old girl with concomitant acute toxoplasmosis is described. Mucormycosis is rare in immunocompetent patients, and hepatic mucormycosis has so far been described only in the context of disseminated disease. The infection resolved spontaneously without surgical debridement and/or appropriate medical therapy with amphotericen B.

Topics: Amphotericin B; Antifungal Agents; Child, Preschool; Female; Humans; Immunocompetence; Liver Diseases; Mucormycosis; Tomography, X-Ray Computed; Toxoplasmosis

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Biopsy; Cholestasis; Diagnosis, Differential; Fatal Outcome; Granuloma; Histoplasmosis; Humans; Liver; Liver Diseases; Male

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Female; Humans; Leukemia, Promyelocytic, Acute; Liver Diseases; Splenic Diseases

Four patients with cryptococcal meningitis were treated with amphotericin B colloidal dispersion because of nephrotoxicity from prior treatment with conventional amphotericin B. The limited experience presented here suggests that amphotericin B colloidal dispersion is efficacious for the treatment of cryptococcal meningitis, despite being undetectable in cerebrospinal fluid, and offers a potential therapeutic alternative for patients who cannot tolerate conventional amphotericin B.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Colloids; Diabetes Mellitus, Type 2; Heart Transplantation; Humans; Liver Diseases; Male; Meningitis, Cryptococcal; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Suspensions

The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer.. The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed.. Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis.. A radiographic syndrome resembling hepatic, splenic, or renal candidiasis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Breast Neoplasms; Candidiasis; Combined Modality Therapy; Female; Fluconazole; Fungemia; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Kidney Diseases; Liver Diseases; Middle Aged; Neutropenia; Retrospective Studies; Splenic Diseases; Syndrome; Tomography, X-Ray Computed; Transplantation, Autologous

The incidence of disseminated candidiasis is increasing. Liver involvement is frequent but rarely diagnosed. The authors report a case of disseminated candidiasis due to Candida glabrata with liver metastases. The presence of hepatic lesions was diagnosed by CT scan and parasitological examination of liver abscess contents obtained by CT-scan-directed puncture-aspiration. The outcome was favorable with amphotericin-B (cumulative dose of 1 g) and flucytosin. Aspects of hepatic involvement in disseminated candidiasis is discussed, together with the role of Candida glabrata in pathology of this type.

Topics: Aged; Amphotericin B; Candidiasis; Female; Flucytosine; Humans; Liver Abscess; Liver Diseases

To determine whether a prior history of hepatosplenic candidiasis resulted in increased Candida-associated morbidity and mortality after marrow transplant, 15 consecutive patients with biopsy-proven hepatosplenic candidiasis were observed prospectively. All patients received amphotericin B before transplant. Amphotericin B was continued at a dose of 0.5 mg/kg/day from conditioning through marrow engraftment, at which time it was discontinued if computerized tomography (CT) evidence of disease was stable or improved. Patients were observed for progression of candidiasis for the first 100 days after transplant. The amount and duration of antifungal therapy received before transplant varied widely. The majority of patients (73%) had persistently abnormal CT scans before transplant. After transplant, 3 of 15 died (20%) with evidence of fungal disease, although fungal species differed from those diagnosed pretransplant, compared with a historical mortality rate of 90% in posttransplant patients with documented hepatosplenic candida. Comparison CT scans obtained before and after transplant showed improvement in 9 of 15 (60%), complete resolution in 2 of 15 (13%), and none showed progression. We conclude that hepatosplenic candidiasis is not an absolute contraindication to marrow transplant when patients receive amphotericin B therapy before transplant and continue therapy until engraftment is established.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Contraindications; Humans; Liver Diseases; Prospective Studies; Splenic Diseases; Tomography, X-Ray Computed

Two pediatric leukemic patients with hepatosplenic candidiasis during multidrug antileukemic chemotherapy successfully underwent bone marrow transplantation (BMT) after aggressive antifungal chemotherapy employing fluconazole and amphotericin B with or without splenectomy. One patient received allogeneic marrow graft and the other received an autologous graft. One patient has been disease-free for more than 21 months after BMT without any recurrence of Candida infection. The other patient showed tentative reactivation of hepatic lesions just after BMT by CT scanning, but these lesions disappeared again by continuous administration of the antifungal agents. The second patient died of leukemia relapse without recurrence of fungal infection. Our cases indicate the possibility of successful BMT once a fungal infection is well controlled by antifungal chemotherapy and surgical resection.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Child, Preschool; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Splenic Diseases

A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.

Topics: Amphotericin B; Candidiasis; Child, Preschool; Female; Humans; Liposomes; Liver; Liver Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Amphotericin B; Brain Diseases; Candidiasis; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Liver Diseases; Middle Aged; Splenic Diseases

Topics: Adult; Amphotericin B; Candidiasis; Drug Carriers; Female; Focal Infection; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Liposomes; Liver Diseases

Topics: Amphotericin B; Candidiasis; Child; Female; Humans; Liver Diseases; Liver Neoplasms; Sarcoma; Therapeutic Irrigation

A 38-year-old woman with acute myeloid leukaemia developed focal hepatic candidiasis. Ultrasonography and computerised tomography revealed the hepatic lesion and definite diagnosis was established by percutaneous liver biopsy. The use of a cumulative dose of 6.6 g of amphotericin B in combination with 5-fluorocytosine resulted in successful eradication of the fungus. The difficulties in making an antemortem diagnosis are well recognised and optimal therapy of the condition remains to be defined.

Topics: Adult; Amphotericin B; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Remission Induction; Tomography, X-Ray Computed; Ultrasonography

The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects.

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Drug Carriers; Humans; Leukemia; Liposomes; Liver Diseases; Male; Opportunistic Infections; Splenic Diseases

To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment.. Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole.. All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis.. Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Candidiasis; Child; Child, Preschool; Fluconazole; Flucytosine; Humans; Leukemia; Liver Diseases; Remission Induction; Splenic Diseases; Tomography, X-Ray Computed

A 23 year old woman with Philadelphia-positive chronic granulocytic leukaemia underwent a 3/4 HLA identical bone marrow transplantation. During the neutropenic period, a septic condition developed which was caused by Candida albicans. Administration of Amphotericin B for 63 day was ineffective including an attempt to give the drug through the truncus coeliacus. Finally the sepsis disappeared during fluconazole treatment.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Candidiasis; Female; Fluconazole; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Liver Diseases; Splenic Diseases

Topics: Adult; Amphotericin B; Candida albicans; Candidiasis; Drug Administration Schedule; Drug Resistance; Female; Fluconazole; Humans; Liver Diseases; Splenic Diseases

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

Opportunistic fungal infections occur with increasing frequency during chemotherapy induced granulocytopenia. A 27-year-old woman developed mucormycosis in the ileocecal region with fatal dissemination to the liver while receiving consolidation therapy for acute T-lymphoblastic leukemia. The infection occurred during a period of decreased colonization resistance in the intestinal tract. Early symptoms were high fever unresponsive to broad spectrum antibiotics, severe pain in the right lower abdominal quadrant and diarrhoea. This was followed by an infiltrate in the right abdomen, ileus, and icterus. Diagnosis was established in the living patient by thin needle aspiration from affected liver tissue. Giemsa's stain and fungal cultures revealed Mucor indicus. The fatal outcome of disseminated mucormycosis justifies a high index of suspicion and a maximal (invasive) diagnostic effort as localised infections might be cured by resection and amphotericin B.

Topics: Adult; Agranulocytosis; Amphotericin B; Appendix; Cecal Diseases; Female; Flucytosine; Humans; Injections, Intravenous; Liver Diseases; Mucormycosis; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

A murine model of focal hepatic candidiasis which we suggest simulates certain conditions of this clinical variant of systemic candidiasis in leukemic patients is described. We have shown that outbred mice inoculated with Candida albicans by the oral-intragastric route as infants (6 days old) and then immunocompromised by cyclophosphamide and cortisone acetate treatment 2 weeks later demonstrate systemic spread of the opportunistic pathogen to the liver, lungs, spleen, and kidneys. Treatment with the immunosuppressive drugs cyclophosphamide and cortisone acetate resulted in alteration of the normal integrity of the mucosal epithelium of the gut as well as in granulocytopenia. Approximately 55% of the animals with C. albicans infections in the liver demonstrated hepatic abscesses. After these same infected, immunocompromised animals were treated with suboptimal dosages of antifungal agents (cilofungin or amphotericin B), either by intraperitoneal or subcutaneous (s.c.) routes, persistent hepatic abscesses were fewer in number and delimited by a distinct outer layer of host tissue but still contained large numbers of the viable pathogen. Blood cell counts indicated that these antifungal drug-treated animals had reestablished approximately the same number of leukocytes per microliter of blood as estimated prior to the immunocompromising drug treatment. Similar conditions in leukemic patients who were in remission and who were undergoing antifungal drug therapy for systemic candidiasis have been reported. Clearance of hepatic infections in mice was accomplished by using appropriate concentrations of amphotericin B administered by daily intraperitoneal or s.c. injection for 5 to 7 days or cilofungin by continuous s.c. infusion for 7 days. However, systemic antifungal therapy did not significantly reduce numbers of C. albicans cells in the stomach and esophagus. Persistent foci of gastrointestinal colonization by C. albicans, especially in the region of the cardial-atrium fold of the stomach of these mice, are reservoirs of the opportunistic pathogen from which reinfection may occur, leading to relapse of systemic candidiasis.

Topics: Agranulocytosis; Amphotericin B; Animals; Body Weight; Candidiasis; Cortisone; Cyclophosphamide; Disease Models, Animal; Drug Therapy, Combination; Echinocandins; Esophagitis, Peptic; Immune Tolerance; Incidence; Injections, Intravenous; Injections, Subcutaneous; Liver Diseases; Mice; Microbial Sensitivity Tests; Organ Specificity; Peptides; Peptides, Cyclic

Topics: Adolescent; Adult; Amphotericin B; Candidiasis; Female; Humans; Leukemia; Liver Diseases; Middle Aged; Splenic Diseases

Three cases of aspergillosis observed in Pavia Infectious Disease Clinic in 1983-85 are described. The cases differed both in the site of the infection (lungs, bones and liver) and in the patients' basic immunological situation. The importance of mycological investigations during diagnosis is emphasised, though they should of course be flanked by instrumental examinations and blood chemical assays. The efficacy of specific treatment with amphotericin B combined with surgery and plasma exchange is also emphasised.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Female; Humans; Intervertebral Disc; Liver Diseases; Male; Middle Aged; Plasma Exchange; Spinal Diseases

Hepatic candidiasis has been increasingly recognized as a variant of disseminated candidiasis in immunocompromised patients. Five leukemic patients with antemortem diagnosis of hepatic candidiasis are described, and 32 additional cases reported in the literature are reviewed. Cultures of the liver and/or spleen and blood cultures usually give negative results; histopathologic demonstration of Candida organisms in tissue specimens is necessary for a definitive diagnosis. Response to conventional therapy with amphotericin B is poor, and 34.4 percent of the patients died with evidence of active fungal disease. Liposome-encapsulated amphotericin B, which has been successfully used in a limited number of patients with invasive fungal disease, may be an effective and relatively nontoxic drug.

Topics: Adult; Amphotericin B; Biopsy; Candida; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Immunologic Deficiency Syndromes; Ketoconazole; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver; Liver Diseases; Male

Nine patients with hematologic malignancies developed fungal infections, predominantly involving the liver and spleen. Eight patients had biopsy-documented progressive candidiasis and one had an unclassified fungus. The patients were treated with liposomal-amphotericin B (L-AmpB) after their fungal infection progressed during treatment with standard intravenous (IV) AmpB (Fungizone; E. R. Squibb & Son, Princeton, NJ) and/or other antifungals. Eight patients (88.8%) were cured of their fungal infection, and one showed improvement after treatment. Minor acute toxicity and no chronic toxicity were associated with the administration of L-AmpB. L-AmpB is a safe and effective therapeutic method for treating fungal infections that have invaded the liver and spleen even when they are refractory to conventional anti-fungal therapy.

Topics: Adolescent; Adult; Amphotericin B; Candidiasis; Child, Preschool; Female; Humans; Leukemia; Liposomes; Liver Diseases; Lymphoma; Male; Middle Aged; Splenic Diseases

Disseminated fungal disease, predominantly involving liver and spleen, developed in eight patients with hematologic malignancies. Because the patients failed to respond to standard antifungal drugs, they were treated with liposomal amphotericin B (L AmpB). Before therapy began, the diagnosis was confirmed histologically and the patients underwent abdominal computed tomography (CT), which indicated hepatosplenomegaly with or without multiple microabscesses in the liver and spleen. After each course of treatment with L AmpB, patients underwent CT, followed by either open or CT-guided percutaneous aspiration biopsy of the liver. Post-treatment CT showed partial regression of lesions in six patients and persistence in two. In all patients a liver biopsy confirmed that the lesions noted after treatment were due to granulomas or focal areas of fibrosis compatible with healing. Thus, the persistence of multiple defects on enhanced scans in two patients was not an indication of persistent abscesses. Clinical response was an additional important factor. Close clinical and pathologic correlation in addition to CT scanning are required in the follow-up of hepatosplenic fungal infections.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Biopsy; Candidiasis; Child; Female; Humans; Leukemia; Liposomes; Liver; Liver Diseases; Lymphoma; Male; Middle Aged; Splenic Diseases; Tomography, X-Ray Computed

The potential of ketoconazole prophylaxis to antagonize the activity of amphotericin B against aspergilli was investigated in vitro and in neutropenic mice. Exposure of Aspergillus fumigatus (six strains) and of Aspergillus flavus or Aspergillus niger to ketoconazole resulted in a uniform increase of the minimal fungicidal activity of amphotericin B, from 0.15-0.63 mg/liter to greater than 2.5 mg/liter in a microwell assay. To test the relevance of this antagonism in vivo, we challenged neutropenic mice iv with a lethal dose of conidia from two strains of A. fumigatus and then treated the mice first with ketoconazole and then with amphotericin B or amphotericin B plus ketoconazole. Pretreatment with ketoconazole for 48 hr completely abolished the protective effect of a subsequent therapy with amphotericin B, whether ketoconazole therapy was stopped (P less than .001) or not (P less than .001). Ketoconazole given alone had no significant effect on survival. Our data show that ketoconazole not only antagonized the fungicidal activity of amphotericin B in vitro but also abolished in vivo the protective effect of the only drug shown to be useful in the therapy of aspergillosis. The clinical importance of this antagonism, which is not limited to Aspergilli in vitro, requires careful consideration before ketoconazole prophylaxis can be recommended for patients at high risk of developing invasive opportunistic fungal infections.

Topics: Amphotericin B; Animals; Aspergillosis; Disease Models, Animal; Female; Humans; In Vitro Techniques; Ketoconazole; Liver Diseases; Mice; Neutropenia; Premedication

Topics: Amphotericin B; Candidiasis; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Thrombocytopenia

Topics: Amphotericin B; Ampicillin; Animals; Anti-Bacterial Agents; Azaguanine; Cephaloridine; Chloramphenicol; Colistin; Cyclophosphamide; Cycloserine; Erythromycin; Female; Kanamycin; Liver Diseases; Mice; Mitomycins; Penicillins; Polymyxins; Streptomycin; Tetracycline; Viomycin

Topics: Adult; Amphotericin B; Biopsy; Coccidioidomycosis; Eye Diseases; Female; Humans; Liver; Liver Diseases; Radiography, Thoracic

Topics: Amphotericin B; Cricetinae; Liver Diseases; Liver Diseases, Parasitic; Mice; Pharmacology; Research; Schistosomiasis; Schistosomiasis mansoni

Topics: Alkaline Phosphatase; Amphotericin B; Biopsy; Black People; Cryptococcosis; Hepatomegaly; Humans; Liver Diseases; Lymph Nodes; Mesenchymoma; Muscular Diseases; Neoplasms; Serologic Tests; Surgical Procedures, Operative; Thigh

Topics: 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; Animals; Liver Diseases; Male; Mice; Myositis; Sporotrichosis; Temperature

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

Topics: Amphotericin B; Animals; Humans; Liver Diseases; Sheep