amphotericin-b and Splenic-Diseases

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

Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB-PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Daunorubicin; Dimyristoylphosphatidylcholine; Drug Carriers; Female; Follow-Up Studies; Fusarium; Granuloma; Hepatitis; Humans; Immunocompromised Host; Kidney Diseases; Leukemia-Lymphoma, Adult T-Cell; Mycoses; Neutropenia; Phosphatidylglycerols; Prednisone; Recurrence; Splenic Diseases; Vincristine

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Catheters, Indwelling; Female; Hepatic Artery; Humans; Leukemia; Liver Abscess; Male; Mycoses; Portal Vein; Splenic Artery; Splenic Diseases

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

Endogenous fungal endophthalmitis (EFE) caused by disseminated fusariosis is a rare condition that generally has a poor outcome, even with intensive therapy. Here, we describe a case in which this type of EFE was diagnosed with vitreous sampling and was successfully treated with 25-gauge vitrectomy and antifungals, including liposomal amphotericin B and voriconazole. A 16-year-old male patient undergoing treatment for acute myeloid leukemia complained of eye pain and blurred vision in his right eye. Treatment was initiated for a vitreous opacity, possibly associated with herpetic retinitis, but the patient worsened and he was referred to us. Right-eye visual acuity was limited to light perception. We suspected endogenous endophthalmitis and performed 25-gauge vitrectomy with antibiotic perfusion of ceftazidime, vancomycin, and voriconazole. Vitreous culturing revealed the presence of Fusarium solani species complex, and enhanced computed tomography revealed disseminated fusariosis lesions in the lung, spleen, and the soft tissue of the left upper arm. The patient received antifungal treatment with liposomal amphotericin B and voriconazole, and these conditions were eliminated. Visual acuity recovered to 20/400 after additional vitrectomy for tractional retinal detachment and was maintained at this level during the 6-month follow-up period. The success of our treatment allowed the capture of optical coherence tomography images of the retina during fusarium-associated endogenous endophthalmitis and the follow-up period. Furthermore, this case showed that immediate vitrectomy for suspected EFE and intensive treatment can lead to a good clinical outcome.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Dermatomycoses; Endophthalmitis; Fusariosis; Fusarium; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Splenic Diseases; Treatment Outcome; Vitrectomy; Voriconazole

Mucormycosis, a rare opportunistic infection seen in immunocompromised hosts, is caused by fungi of Mucorales family. It may be confined to the organs, such as rhinocerebral and pulmonary mucormycosis, or may cause disseminated infection. A 14-year-old boy presented to our clinic with fever and left upper quadrant abdominal pain, and on evaluation was found to have pancytopaenia, and imaging revealed ill-defined splenic collection with thrombus in the splenic vein. He was started on empirical intravenous antibiotics, followed by antifungals empirically as he did not show any improvement clinically. Eventually, splenectomy was done, which on histopathological examination revealed mucormycosis. The patient finally succumbed to his illness as he developed peritonitis and refractory shock. To date, only two cases of isolated splenic mucormycosis have been reported. Aggressive treatment is needed, which includes the use of antifungals (amphotericin B) and surgical debridement or resection of the involved tissues or organs.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Anti-Bacterial Agents; Antifungal Agents; Fatal Outcome; Humans; Immunocompetence; Male; Mucormycosis; Opportunistic Infections; Rare Diseases; Spleen; Splenectomy; Splenic Diseases; Tomography, X-Ray Computed

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

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis, Invasive; Chemotherapy-Induced Febrile Neutropenia; Cytarabine; Daunorubicin; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Hepatitis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Splenic Diseases; Tomography, X-Ray Computed

Amphotericin B (AmB), is a highly effective antileishmanial agent used as first-line treatment in different formulations in visceral leishmaniasis endemic areas of Bihar, India. However, parenteral infusion, prolonged hospitalization, and toxicity are major hurdles. Our previous work demonstrated the efficacy and stability of functionalized carbon nanotubes as a delivery mechanism for AmB. In this study, using the hamster model, we have shown that this novel formulation of AmB can be administered orally, resulting in 99% inhibition of parasite growth following a 5-day course at 15 mg/kg body weight.

Topics: Administration, Oral; Amphotericin B; Animals; Antiprotozoal Agents; Chemistry, Pharmaceutical; Cricetinae; Drug Carriers; Leishmania donovani; Leishmaniasis, Visceral; Male; Nanotubes, Carbon; Parasite Load; Splenic Diseases

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Caspofungin; Combined Modality Therapy; Echinocandins; Humans; Hyphae; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Leukemia, B-Cell; Lipopeptides; Male; Middle Aged; Neutropenia; Spleen; Splenectomy; Splenic Diseases; Triazoles

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Endocarditis, Bacterial; Fatal Outcome; Female; Hepatic Encephalopathy; Humans; Liver Abscess; Middle Aged; Splenic Diseases; Tomography, X-Ray Computed; Treatment Failure; Ultrasonography

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

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

Hepatosplenic microabscesses secondary to invasion by various organisms may result in life-threatening conditions, especially in patients with cancer. Whether these patients should continue ongoing cytotoxic therapy, which might result in neutropenia, with the risk of progressive abscess formation or fungemia, remains a dilemma. We report five cases of pediatric acute leukemia with hepatosplenic microabscesses in children aged 4 years to 18 years. These patients presented with prolonged fever and neutropenia after antineoplastic chemotherapy, followed by abdominal pain, hepatosplenomegaly and hepatic dysfunction. Abdominal ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated multiple small lesions compatible with hepatosplenic candidiasis in all of the patients. Cultures, including blood or stool cultures, were positive in only two cases. Treatment with intravenous antifungal agents, including amphotericin B, liposomal amphotericin B, and/or fluconazole were successful in two cases. These two patients remained event-free and survived for more than 24 months (20 months and 22 months after infection was diagnosed). The duration of systemic antifungal medication administration ranged from 3 months to 22 months. The serial image examinations revealed drastic reductions in small residual lesions in the two patients who survived the longest. The major issues for these patients were how long the antifungal therapy should be administered for, and how to select the optimal drug and dosage to avoid hepatic and renal toxicity. Among our patients, alternative therapy with amphotericin B, liposomal amphotericin B, and fluconazole was used according to the patients' conditions, and the duration of antifungal therapy was determined by clinical manifestations and imaging study changes.

Topics: Abscess; Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Administration Schedule; Humans; Leukemia; Liver Abscess; Male; Splenic Diseases

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Hepatitis; Humans; Leukemia; Lung Diseases, Fungal; Opportunistic Infections; Osteomyelitis; Pyrimidines; Remission Induction; Sacroiliac Joint; Splenic Diseases; Triazoles; Voriconazole

Mucormycosis is an uncommon and frequently fatal fungal infection. It characteristically affects patients with diabetes mellitus or patients with severe immunosuppression. The hallmark of mucormycosis infection is tissue infarction and vascular invasion. We present clinical data and imaging studies of a 16 year-old child with acute lymphoblastic leukemia complicated by disseminated mucormycosis resulting in a pseudoaneurysm of the spleen. This was successfully managed by a combination of systemic antifungal therapy (Amphotericin B) and surgery (splenectomy). This entity has not been described in the literature.

Topics: Adolescent; Amphotericin B; Aneurysm, False; Antifungal Agents; Female; Humans; Leukemia, Lymphoid; Mucormycosis; Splenectomy; Splenic Diseases

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

We report a 26-year-old male patient with acute myelocytic leukemia and hepatosplenic candidiasis during his clinical course. His hepatosplenic candidiasis was refractoty to itraconazole and fluconazol. He developed serious side-effect such as renal dysfunction, when conventional amphotericin B was given. Then he was treated with liposomal amphotericin B (Abelcet). This therapy was safe and effective for him. He was able to be treated with 3075 mg of a liposomal amphotericin B. This was ten times as much as the dose of conventional amphotericin B which was given earlier until amphotericin B was stopped because of renal dysfunction. Liposomal amphotericin B seems to be a safe and effective therapy for systemic fungal infectin and should be considered more in Japan.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Humans; Leukemia, Myeloid, Acute; Liposomes; Liver Abscess; Male; Splenic Diseases

A sensitive, culture-based, microtitration technique has recently been developed for determining parasite burdens in organs recovered from Balb/c mice infected with Leishmania infantum. In the present study, this technique was used to examine the efficacy of three, first-line, antileishmanial agents in reducing parasite burdens and eradicating parasites from target organs in mice. Treatment with meglumine antimoniate (50 mg SbV/kg.day) significantly reduced the parasite burdens in the livers and lungs (by about 10-fold and > 100-fold, respectively) but not those in the spleens. Although use of a higher dose of meglumine antimoniate (200 mg SbV/kg.day) resulted in an even more dramatic reduction in the parasite burdens in the livers, it had no significant effect on the burdens in the spleens. Treatment with amphotericin B (0.8 mg/kg every other day) resulted in significant reductions in the parasite burdens in the livers, spleens and lungs of infected mice. Although low doses of aminosidine (20 mg/kg.day) had no effect, high doses (200 mg/kg.day) resulted in undetectable parasite burdens in the livers, for at least 100 days post-treatment, and marked reductions in burdens in the spleens. These results are consistent with previous data from studies using animal models of visceral leishmaniasis. Thanks to the sensitivity of the technique, culture microtitration revealed that none of the drug schedules achieved the elimination of all parasites in all target organs. The murine model used mimics some important features of HIV/Leishmania infantum co-infections in humans.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Female; Leishmania infantum; Leishmaniasis, Visceral; Liver Diseases, Parasitic; Lung Diseases, Parasitic; Meglumine; Meglumine Antimoniate; Mice; Mice, Inbred BALB C; Organometallic Compounds; Parasitology; Paromomycin; Splenic Diseases

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

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

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

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

Hepatosplenic candidiasis is increasingly observed in patients with a haematological malignancy who have received chemotherapy. A case history is described of a male aged 45 who developed symptoms of hepatosplenic candidiasis caused by Candida tropicalis after treatment for acute myeloid leukaemia. The disease is characterized by persistent fever after recovery of the leukopenia induced by the chemotherapy. Echographic and computer-tomographic examination may reveal abscess patterns specific of Candida in the liver. Treatment consists of amphotericin B intravenously or fluconazole orally. Protracted treatment is frequently required.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Drug Therapy, Combination; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Male; Middle Aged; Splenic Diseases

A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic-guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses.

Topics: Abscess; Adult; Amphotericin B; Catheterization; Female; Humans; Leukemia, Promyelocytic, Acute; Liver Abscess; Portal Vein; Splenic Diseases

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

Topics: Amphotericin B; Antineoplastic Agents; Candidiasis; Disease Susceptibility; Hepatitis; Humans; Neoplasms; Splenic Diseases

Despite the large number of organ transplants performed yearly, to date there have been no reports of candidal splenic abscess. We describe here the first case of candidal splenic abscess in a renal transplant recipient treated successfully by splenectomy and amphotericin B. Despite a lengthy illness, the patient recovered with preservation of renal function.

Topics: Abscess; Amphotericin B; Candidiasis; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Splenic Diseases

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

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

In an 18-month period candidal splenic abscesses were diagnosed and treated in eight patients. Predisposing factors consisted of recent exposure to cytotoxic chemotherapy, long-term use of prednisone, neutropenia, antibiotic therapy for greater than three weeks, and gastrointestinal tract colonization with Candida. The patients had a clinical profile of nontoxic appearance with a temperature of more than 38.5 degrees C that was unresponsive to antibiotics, pain and tenderness over the upper abdominal quadrants, focal defects visualized on ultrasound and/or computed tomographic scans, and an elevated alkaline phosphatase level. Candida infection was confirmed by histologic examination of the liver and/or spleen in all patients. Diagnosis was made by percutaneous biopsy in one patient and exploratory laparotomy in seven. Five patients had splenectomy and antifungal drugs. In three patients the fungal abscesses resolved with amphotericin B therapy alone. Seven of eight patients were cured of their splenic abscesses, and five of eight were long-term survivors.

Topics: Abscess; Adolescent; Adult; Amphotericin B; Candidiasis; Child, Preschool; Diagnosis, Differential; Female; Flucytosine; Follow-Up Studies; Humans; Immunosuppression Therapy; Liver Abscess; Male; Middle Aged; Splenic Diseases; Tomography, X-Ray Computed; Ultrasonography

We have reported a case of fungal splenic abscess caused by Blastomyces dermatitidis. Splenic abscess is an uncommon disorder, and fungus as the causative organism is rare. The diagnosis of splenic abscess can be rapidly made with radionuclide and CT scanning and ultrasonography. Splenectomy with appropriate antifungal chemotherapy is the currently recommended therapy.

Topics: Abscess; Adult; Amphotericin B; Blastomyces; Blastomycosis; Humans; Male; Spleen; Splenectomy; Splenic Diseases; Splenic Rupture

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

A thrush-like oral infection with subsequent alveolar abscess formation and a positive blood culture due to Trichosporon capitatum developed in a patient with acute myelogenous leukaemia. Later T. capitatum was identified by indirect immunofluorescence in multiple splenic abscesses. The infection was controlled by immediate aggressive treatment with amphotericin B, flucytosine and rifampicin and by splenectomy. This case of systemic T. capitatum infection resembles somewhat the invasive mycosis due to candida.

Topics: Abscess; Adult; Amphotericin B; Blood; Female; Flucytosine; Humans; Leukemia, Myeloid, Acute; Mitosporic Fungi; Mycoses; Rifampin; Splenic Diseases

Two patients with acute leukemia were found to have candidal splenic abscesses. Both patients were in remission and had normal granulocyte counts at the time the abscesses became evident. Both patients were treated with splenectomy and antifungal therapy with a definite response. The incidence and treatment of fungal splenic abscesses in leukemia patients is discussed with emphasis on the role of splenectomy.

Topics: Abscess; Acute Disease; Amphotericin B; Candidiasis; Humans; Infant; Leukemia; Leukemia, Lymphoid; Male; Splenectomy; Splenic Diseases

Between January 1974 and July 1976, three adult patients with leukemia, therapy-associated granulocytopenia and febrile courses unresponsive to broad spectrum antibiotic therapy were operated upon for a preoperative diagnosis of candidal abscess of the spleen. The diagnosis was based upon a high index of suspicion of invasive candidiasis in this immunosuppressed group of patients; the failure of the patients to respond to the empiric administration of broad spectrum antibiotics, salicylates and steroids, and the presence of discrete scintiscan defects on liver-spleen scan with both 99Tc sulfur colloid and 67Ga citrate. Multiple splenic abscesses containing candidal organisms were confirmed in all three patients, and two of the three also had multiple small abscesses of the liver. The fourth patient, whose liver-spleen scintiscans were abnormal only in showing splenomegaly and whose febrile course responded to aspirin, did not have a candidal abscess of the spleen at the time of celiotomy which was undertaken for fever of unknown cause. The antemortem diagnosis and treatment of candidal splenic abscess in patients with leukemia is dependent upon a high index of suspicion and appropriate clinical correlation with diagnostic tests. Although the prophylactic oral administration of mycostatin to patients at high risk may prevent this once fatal complication, only prompt and aggressive treatment can cure it.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Candidiasis; Female; Humans; Leukemia; Male; Middle Aged; Splenic Diseases