amphotericin-b and Leukemia--Myeloid--Acute

Cases of invasive Trichosporon infections have increasingly emerged; it is now the second leading cause of yeast bloodstream infections after Candida spp., particularly in the immunosuppressed population, where it often causes breakthrough fungemia with high mortality.. We present a case report of a breakthrough Trichosporon asahii infection in a patient with acute myeloid leukemia and review all of the cases of breakthrough Trichosporon spp. infections published in the literature to date.. We extracted 68 cases of breakthrough Trichosporon spp. infections, wherein 95.5% patients had hematological malignancy, 61.8% of them occurred in the presence of echinocandins, 22% of triazoles, 13.2% of amphotericin and 3% of other combinations of antifungals. The most prevalent manifestation was fungemia (94%); 82.8% of these were associated with the presence of a central venous catheter. The overall mortality was 68.7%; the patients who survived recovered from the neutropenic event.. Invasive trichosporonosis is an acute fatal condition that occurs in immunosuppressed patients, usually under antifungal selective pressure. Typically, neutropenia and its underlying diseases are associated with adverse outcomes.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Venous Catheters; Echinocandins; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mortality; Neutropenia; Triazoles; Trichosporon; Trichosporonosis; Voriconazole

BACKGROUND Mucormycosis is a serious, potentially fatal fungal infection caused by species in the Mucorales order. Together with candidiasis and aspergillosis, it is one of the most significant fungal infection that carries a high rate of mortality. Early detection and initiation of antifungal therapy with adequate surgical debridement improves the clinical outcome. CASE REPORT We describe a case of mucormycosis in a patient with acute myeloid leukemia who developed disseminated lung disease with muscular involvement without any cutaneous manifestation. Successful treatment was achieved with surgical debridement, amphotericin B lipid-complex and posaconazole step-down therapy. CONCLUSIONS Mucormycosis can present in various clinical scenarios. Key to diagnosis depends on tissues diagnosis from the affected system, as was done with lung and muscle biopsy in our patient. Clinicians should maintain high suspicion for early diagnosis and prompt treatment.

Topics: Amphotericin B; Antifungal Agents; Female; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Middle Aged; Mucormycosis; Muscular Diseases; Opportunistic Infections

Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking.. We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder.. Of the 19 cases of invasive T asahii infection, the most commonly reported underlying hematologic disorder was acute lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most of the patients (94%) had neutropenia, defined as an absolute neutrophil count of <500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19 cases, and micafungin use was reported in 5 cases. Treatment regimens frequently included voriconazole monotherapy (47%) or the combination of an azole antifungal with amphotericin B (35%). The mortality rate was 58%.. Recognizing that echinocandins, which are increasingly used for prophylaxis in patients with a hematologic malignancy, are not active against Trichosporon species is of critical importance. The recommended first-line therapy for trichosporonosis is voriconazole, but successful outcome depends largely on the underlying immune status of the host.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Drug Therapy, Combination; Echinocandins; Female; Humans; Immunocompromised Host; Invasive Fungal Infections; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporonosis; Voriconazole

Fusarium spp. causes infections mostly in patients with prolonged neutropenia. We describe the case of a disseminated Fusarium solani infection in a patient with acute myeloid leukemia which never reached complete remission during its clinical course. The patient had profound neutropenia and developed skin nodules and pneumonia in spite of posaconazole prophylaxis. F. solani was isolated from blood and skin biopsy, being identified from its morphology and by molecular methods. By broth dilution method, the strain was resistant to azoles, including voriconazole and posaconazole, and to echinocandins. MIC to amphotericin B was 4 mg/L. The patient initially seemed to benefit from therapy with voriconazole and amphotericin B, but, neutropenia perduring, his clinical condition deteriorated with fatal outcome. All efforts should be made to determine the correct diagnosis as soon as possible in a neutropenic patient and to treat this infection in a timely way, assuming pathogen susceptibility while tests of antimicrobial susceptibility are pending. A review of the most recent literature on invasive fungal infections is reported.

Topics: Adult; Amphotericin B; Antifungal Agents; Blood; Fatal Outcome; Fusariosis; Fusarium; Humans; Leukemia, Myeloid, Acute; Lung; Male; Microbial Sensitivity Tests; Microbiological Techniques; Radiography, Thoracic; Skin; Tomography, X-Ray Computed; Triazoles

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine-based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin-B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Venous Catheters; Drug Resistance, Fungal; Echinocandins; Fatal Outcome; Female; Geotrichosis; Geotrichum; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Italy; Leukemia, Myeloid, Acute; Liver; Lung; Lymphoma, Mantle-Cell; Male; Microbial Sensitivity Tests; Middle Aged; Spleen; Tomography, X-Ray Computed; Young Adult

Fusarium, a hyphomyocetous fungus, is often isolated from the environment as a laboratory contaminant, but is also known as a pathogen causing keratomycosis, onychomycosis, and opportunistic infection of the skin and viscera. We report a 67-year-old man with localized cutaneous fusariosis of the scrotum, as a complication of acute myeloid leukemia (AML) under chemotherapy. An induration of 25 mm in diameter, which was covered by necrosis and black crust and with pain upon pressure, was found on the scrotum. Direct microscopic examination of the necrosis showed numerous fungal elements. Culture on Sabouraud dextrose agar with cycloheximide yielded a floccose, grayish white colony. Microscopically, crescent-shaped macroconidia and oval microconidia were abundant. The fungus was identified using gene analysis as Fusarium falciforme of the Fusarium solani species complex. The lesion was treated by voriconazole (total dose: 66,180 mg) and was reduced to 15 mm in diameter. Other metastatic lesions did not appear. After 4 months from the first visit to our department, the patient died of AML. It is believed that the treatment in the early stage of infection prevented further extension of the lesion. During examination of necrotic lesions occurring on the skin of patients with hematological malignancies, it is important to include mycological examination for opportunistic fungal infections, such as aspergillosis or fusariosis, which are easily overlooked by routine culture methods using conventional media with cycloheximide. This paper summarizes cases of cutaneous fusariosis in Japan.

Topics: Aged; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fatal Outcome; Fusariosis; Fusarium; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Opportunistic Infections; Scrotum; Skin; Voriconazole

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

Emerging fungal pathogens, such as Geotrichum capitatum, are often associated with poor prognosis and represent a new challenge in modern medicine. Invasive Geotrichum capitatum infection is rare and has been reported exclusively in patients who showed signs of severe immunodeficiency, particularly those affected by haematological malignancies. The optimal therapy against systemic geotricosis has not yet been identified due to limited data about its antifungal susceptibility. The use of several therapeutic strategies and the low number of cases treated does not allow identification of specific therapeutic protocols. Furthermore, in spite of antifungal therapy, mortality rates reach very high levels. We report a case of systemic Geotrichum capitatum infection in a 78-year-old male treated with salvage therapy after acute myeloid leukaemia (AML) relapse. Geotrichum capitatum was isolated from his blood culture and identified by using Vitek 2 and Maldi time-of-flight system (MALDI-TOF). The infection was unsuccessfully treated, despite in vitro susceptibility, with micafungin and liposomal amphotericin B.

Topics: Aged; Amphotericin B; Antifungal Agents; Coma; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Geotrichum; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Recurrence; Sepsis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Treatment Failure

During chemotherapy for bilineal leukemia, a 6-month-old infant presented with a necrotizing skin and soft-tissue infection of the chest wall due to Rhizopus sp. Successful outcome was achieved by systemically administered liposomal amphotericin B and local wound control with the novel administration of topical deoxycholate amphotericin B and surgical resection.

Topics: Administration, Topical; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Fatal Outcome; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mucormycosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhizopus

Despite the availability of newer antifungal drugs, outcomes for patients with invasive fungal infections (IFIs) continue to be poor, in large part due to delayed diagnosis and initiation of appropriate antifungal therapy. Standard histopathologic diagnostic techniques are often untenable in at-risk patients, and culture-based diagnostics typically are too insensitive or nonspecific, or provide results after too long a delay for optimal IFI management. Newer surrogate markers of IFIs with improved sensitivity and specificity are needed to enable earlier diagnosis and, ideally, to provide prognostic information and/or permit therapeutic monitoring. Surrogate assays should also be accessible and easy to implement in the hospital. Several nonculture-based assays of newer surrogates are making their way into the medical setting or are currently under investigation. These new or up-and-coming surrogates include antigens/antibodies (mannan and antimannan antibodies) or fungal metabolites (d-arabinitol) for detection of invasive candidiasis, the Aspergillus cell wall component galactomannan used to detect invasive aspergillosis, or the fungal cell wall component and panfungal marker β-glucan. In addition, progress continues with use of polymerase chain reaction- or other nucleic acid- or molecular-based assays for diagnosis of either specific or generic IFIs, although the various methods must be better standardized before any of these approaches can be more fully implemented into the medical setting. Investigators are also beginning to explore the possibility of combining newer surrogate markers with each other or with more standard diagnostic approaches to improve sensitivity, specificity, and capacity for earlier diagnosis, at a time when fungal burden is still relatively low and more responsive to antifungal therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; beta-Glucans; Biomarkers; Female; Fusariosis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Meta-Analysis as Topic; Mycoses; Opportunistic Infections; Polymerase Chain Reaction

In this review, we aim to compare different early treatment strategies of invasive fungal diseases in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Three treatment approaches--prophylactic, empiric, and preemptive treatment--are subject to continuous discussion among physicians treating patients at risk. Considering the available clinical basis of evidence, we opt for antifungal prophylaxis with posaconazole 200 mg tid po as our primary prophylactic strategy, while the employment of preemptive treatment should be delayed until more accurate diagnostic tools become available. In addition to antifungal prophylaxis, empiric treatment with caspofungin or L-AmB may be administered to patients with fever resistant to broad-spectrum antibiotic treatment and without radiographic findings typical of invasive fungal disease.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Caspofungin; Clinical Trials as Topic; Drug Resistance, Fungal; Echinocandins; Fever; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Medical Oncology; Mycoses; Myelodysplastic Syndromes; Triazoles

Topics: Acyclovir; Aged; Amphotericin B; Antifungal Agents; Antiviral Agents; Aspergillosis; Fatal Outcome; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Mouth Diseases; Paranasal Sinus Diseases; Pyrimidines; Triazoles; Voriconazole

Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined.. The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies.. There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC.. The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Chronic Disease; Fluconazole; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Salvage Therapy; Time Factors

Fungal infections caused by Fusarium in the immunocompromised host are highly resistant to all antifungal agents. Fusarium endocarditis is a rare and usually fatal disease. We report an immunocompromised child who survived Fusarium solani endocarditis despite the in vitro resistance of the organism to all available antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Endocarditis; Female; Follow-Up Studies; Fungemia; Fusarium; Humans; Immunocompromised Host; Infant; Leukemia, Myeloid, Acute; Liposomes; Opportunistic Infections; Pyrimidines; Risk Assessment; Treatment Outcome; Triazoles; Voriconazole

Topics: Acute Kidney Injury; Adult; Amphotericin B; Aspergillosis; Dose-Response Relationship, Drug; Fatal Outcome; Female; Humans; Leukemia, Myeloid, Acute; Male; Treatment Outcome

Blastoschizomyces capitatus infection in a 48-year-old man with acute myelocytic leukaemia is reported. A multiorgan involvement and fulminant course of the fungal infection resulted in the patient's death despite fluconazole prophylaxis, therapy with amphotericin B and administration of granulocyte colony-stimulating factor. Predisposing factors to the infection, clinical relevance of surveillance strains and in vitro antifungal susceptibility testing are discussed.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Mitosporic Fungi; Multiple Organ Failure; Mycoses

A girl with resistant acute myeloid leukemia (AML) had a stem cell transplantation. Preceding transplantation, she had recurrent pneumonitis. No causative agent was identified. Despite several antibiotics including high-dose liposomal amphotericin-B, pulmonary infection progressed. Aspergillosis, always considered, could not be documented. She died from cardiac arrest on the second day after transplantation, with no forewarning of previous heart disease. Pericardial and myocardial aspergillosis was an autopsy finding. Pericardial and myocardial aspergillosis, rare manifestations of systemic aspergillosis, should be considered in any immunocompromised patient with long-lasting pulmonary infection, even in the absence of specific cardiac findings.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Child; Fatal Outcome; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Myocarditis; Pericarditis

We report a case of fatal disseminated fungal infection by Scedosporium prolificans which occurred in a patient with acute leukemia during induction chemotherapy. Rapid clinical deterioration despite high-dose empirical amphotericin B highlights both the pathogenicity of this fungus in immunocompromised hosts and its resistance to standard antifungal therapy.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Resistance, Microbial; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Mycetoma; Pseudallescheria

The observation of pulmonary mucormycosis occurring in a patient presenting with aplasia induced therapeutically during treatment for acute myeloblastic leukaemia, has led to a review of the characteristics of this rare opportunistic fungal infection: it occurs in a particular condition; the clinical manifestations are characterised by the thrombotic character and the rapidly necrosing nature of the histological lesions; the diagnosis is usually very difficult to make and is linked to the rarity of the pathology and the frequently negative mycological specimens apart from tissue biopsies; the value of a medicosurgical therapeutic strategy on which the prognosis of the infection depends.

Topics: Amphotericin B; Antifungal Agents; Bronchoalveolar Lavage Fluid; Bronchoscopy; Hemoptysis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Necrosis; Opportunistic Infections; Prognosis; Pulmonary Embolism; Tomography, X-Ray Computed

A case of disseminated invasive fusarial infection (DFI) with sinus involvement in a patient with acute myeloblastic leukaemia is reported. Amphotericin B with rifampin were administrated and wide radical sinus surgery was performed. Nevertheless, the patient died six weeks later. The four principal forms of fusarial infections in humans are discussed: toxicosis, allergic fungal sinusitis, locally invasive infection, and disseminated invasive infection. Prognosis of DFI in the immunocompromised host is usually poor, and treatment is difficult. Profound and prolonged neutropaenia appears to be the major predisposing factor. The literature on infections caused by Fusarium species in immunocompromised hosts is reviewed, especially those where the sinuses were involved.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Fusarium; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Opportunistic Infections; Sinusitis

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Drug Resistance, Microbial; Fatal Outcome; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

To report a patient with intolerance to amphotericin B reversed by preparing the antifungal in fat emulsion 20% and to review the medical literature on innovative formulations of amphotericin B.. A 51-year-old man diagnosed with acute myelogenous leukemia was treated with standard induction chemotherapy. Empiric antibiotic therapy was initiated 2 days postchemotherapy; however, the patient continued to be febrile until day 7. At this time amphotericin B 35 mg/250 mL D5W over 4 hours was administered. Despite premedication, the patient experienced severe rigors, chills, and fever. As the result of continuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusion-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsion 20% was administered over 2 hours after patient consent was obtained. Premedication was administered and the patient tolerated therapy without adverse events. Amphotericin B dosage escalations to 50 and 70 mg were tolerated similarly. During this treatment the patient became afebrile and the serum creatinine concentration decreased to normal.. Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the empiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents characteristically prescribed in these patients. Furthermore, infusion-related events, if not intolerable, can dramatically reduce the patient's quality of life. For these reasons, novel means of amphotericin B administration are being explored.. The delivery of amphotericin B in a lipid diluent may have substantial benefit in reducing the nephrotoxicity and infusion-related events associated with the antifungal. Prospective clinical trial comparing lipid-complexed amphotericin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.

Topics: Amphotericin B; Drug Interactions; Fat Emulsions, Intravenous; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Middle Aged

This case report describes a patient with acute myelocytic leukaemia, who developed a necrotizing bronchial aspergillosis. This is an uncommon, new form of invasive aspergillosis, which is mainly seen in the heart-lung transplantation setting and has only been reported once in another patient with leukaemia. Neither amphotericin B nor liposomal amphotericin (AmBisome) was effective. Only after the immune system had recovered did the infection disappear.

Topics: Amphotericin B; Aspergillosis; Bronchial Diseases; Bronchoscopy; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Necrosis; Radiography

Mucormycosis (phycomycosis, zygomycosis) is an acute opportunistic infection caused by a saprophytic fungus found in soil, bread molds, and decaying fruits and vegetables. Numerous predisposing risk factors are associated with mucormycosis, although most cases have been reported in poorly controlled diabetics or in patients with hematologic malignant conditions. This report presents two cases of oral mucormycosis. One case occurred in the maxilla in a patient with well-controlled diabetes. The other involved the mandible and overlying gingiva in a patient with acute myelogenous leukemia. A review of the literature concerning oral mucormycosis is also presented.

Topics: Adult; Aged; Amphotericin B; Candidiasis, Oral; Diabetes Complications; Gingival Diseases; Humans; Leukemia, Myeloid, Acute; Male; Mandibular Diseases; Maxillary Diseases; Mouth Diseases; Mucormycosis

Candida species are an uncommon cause of infectious arthritis, although the frequency has increased during recent years. Three cases of septic arthritis caused by Candida species are reported, and the literature is reviewed. The first patient developed a popliteal cyst infected by Candida albicans after multiple intravenous antibiotic treatments. The second patient had acute myelogenous leukemia and experienced knee arthritis after chemotherapy, and the third suffered oligoarthritis after a second heart transplantation. All patients received treatment with a standard dose of intravenous amphotericin B. Responses were achieved only in the first two cases; the third patient died despite therapy. Thirty-six previously reported Candida arthritis cases are reviewed, and epidemiologic, diagnostic, therapeutic, and prognostic features are analyzed. Cases are divided into two categories: direct inoculation of fungus and hematogenously disseminated disease; these two categories are compared in terms of sex, age, pathogen species, treatment, and survival. Arthritis induced through direct inoculation of fungus is seen in older individuals, is more frequently produced by species other than C albicans (Candida parapsilosis especially), and has a better prognosis than arthritis caused by disseminated candidiasis. Arthritis can be resolved even in the persistence of the systemic disease. It is believed that the first case of Baker's cyst infected by C albicans and the first case of Candida arthritis in a heart transplant patient are reported here.

Topics: Adolescent; Adult; Amphotericin B; Arthritis, Infectious; Candidiasis; Female; Heart Transplantation; Humans; Immunocompromised Host; Injections, Intra-Articular; Knee Joint; Leukemia, Myeloid, Acute; Male; Middle Aged; Popliteal Cyst; Postoperative Complications; Radiography

We present six cases of fusariosis caused by Fusarium solani that were diagnosed over a three-year period in 166 adult patients undergoing chemotherapy for acute leukemia. Necrotic skin lesions were evident in four patients, fungemia in three, and a deep cellulitis around a great toe nail at the time of a febrile illness in two. The mean minimal inhibitory concentration (MIC) of amphotericin B was 3.3 micrograms/mL and of miconazole, 5.3 micrograms/mL; all isolates were resistant to 5-fluorocytosine. All patients received amphotericin B (1.0-1.5 mg/kg per d) plus 5-fluorocytosine. In contrast to results found in the literature, five patients had resolution of their infections, and the one patient who died had necropsy evidence of disseminated fusariosis. Review of our cases and of the literature did not reveal a definitive source for the organism or its portal of entry. Fusarium spp. must be recognized as opportunistic pathogens that cause a potentially fatal infection in compromised patients.

Topics: Adult; Amphotericin B; Female; Flucytosine; Fusarium; Humans; Immune Tolerance; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Prolymphocytic; Male; Middle Aged; Mycoses; Opportunistic Infections

A neutropenic patient with acute myeloid leukemia developed nasal and perinasal infection caused by the fungus Exserohilum rostratum. Early amphotericin B treatment along with marrow recovery resulted in resolution of the infection. A review of other previously reported cases of Exserohilum and Bipolaris infections show a favourable outcome in most patients who receive systemic antifungal treatment with amphotericin B.

Topics: Agranulocytosis; Amphotericin B; Humans; Immune Tolerance; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitosporic Fungi; Mycoses; Nasal Mucosa; Neutropenia; Nose Diseases; Paranasal Sinus Diseases

Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy.

Topics: Adult; Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Prospective Studies; Treatment Outcome

Invasive fungal infections (IFI) are a major cause of infection-related mortality during induction chemotherapy of acute leukemia (AL) patients. Data on antifungal prophylaxis (AFP) in children are limited by retrospective design, small sample size, and variability of chemotherapy phases having different risk of IFI. There are no data comparing voriconazole versus amphotericin B (AmB) as AFP in either adult/pediatric AL. The objectives of this study were to compare efficacy and toxicity of AmB and voriconazole as AFP in pediatric AL patients.. As a pilot study, total 100 children (≤15 y) with denovo acute myeloid leukemia and acute lymphoblastic leukemia were randomized to either oral voriconazole or low dose intravenous AmB as AFP during induction chemotherapy.. Failure of prophylaxis occurred in 14/50 patients in voriconazole arm (1 proven mucormycosis, 1 possible IFI, 11 empirical antifungal therapy, and 1 withdrawal owing to hepatotoxicity) and 17/50 patients in AmB arm (3 possible IFI, 13 empirical antifungal therapy, and 1 withdrawal owing to difficult venous access) (P=0.66). Of the 29 patients who had failure of prophylaxis unrelated to drug toxicity, computed tomography of the chest showed infiltrates in 10 patients with 3/12 in voriconazole arm and 7/16 in AmB arm (P=0.43). Drug-related serious adverse events were 6% versus 30% in voriconazole and AmB arms, respectively (P<0.01). Further, total number of toxicities per patient in AmB arm were significantly higher as compared with voriconazole arm (P<0.0001).. This is the first randomized study comparing voriconazole with AmB in pediatric AL patients as AFP during induction chemotherapy; our results showed that oral voriconazole seems to be comparable with AmB with less toxicity and more convenience. (ClinicalTrials.gov identifier: NCT00624143).

Topics: Administration, Oral; Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Mycoses; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Caspofungin; Child; Child, Preschool; Drug Therapy, Combination; Echinocandins; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Male; Middle Aged; Mycoses; Neutropenia; Prospective Studies; Pyrimidines; Transplantation Conditioning; Triazoles; Voriconazole; Young Adult

The objective of this study was to assess the costs and effectiveness (avoided invasive fungal infections - IFIs; overall mortality) of prophylaxis with posaconazole 200 mg per os TID and standard azoles (fluconazole 400 mg per os OD, itraconazole 200 mg per os BID) in neutropenic patients with acute myelogenous leukaemia or myelodysplastic syndromes. A 100-day cost-effectiveness model was developed following the Italian hospital perspective. The probability of IFIs, death from IFIs, and death from other causes was obtained from the literature. Health care sector resources (type, volume, unit cost) are given in Euros and refer to 2009. The robustness of the cost-effectiveness model was tested via one-way and probabilistic sensitivity analyses. Total costs for posaconazole (standard azoles) was estimated at Euros 3365.26 (Euros 2339.96). Posaconazole is consistently more effective than standard azoles. The incremental cost-effectiveness ratio for avoided IFI (avoided overall mortality) with posaconazole is Euros 15,850.51 (Euros 18,038.43). Sensitivity analyses confirmed the robustness of such findings. In conclusion, posaconazole as a prophylaxis in neutropenic patients with AML or MDS who are at risk of IFI is good value for money for Italian hospitals.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Deoxycholic Acid; Drug Combinations; Drug Costs; Equipment and Supplies; Fluconazole; Follow-Up Studies; Hospital Costs; Humans; Immunocompromised Host; Infusions, Intravenous; Italy; Itraconazole; Leukemia, Myeloid, Acute; Mycoses; Myelodysplastic Syndromes; Neutropenia; Oncology Nursing; Treatment Outcome; Triazoles

The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population.. Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability.. The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups.. ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fungemia; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Myelodysplastic Syndromes; Primary Prevention; Probability; Prognosis; Remission Induction; Risk Assessment; Single-Blind Method; Survival Analysis; Treatment Outcome

The incidence of fungal infections and the role of liposomal amphotericin B (Ambisome) in proven and probable infections were evaluated in acute leukemic patients, intolerant to conventional amphotericin B. During 1999-2002, 307 febrile episodes occurred in 231 patients. Fungi were responsible for 3% of bloodstream infections. Ambisome was employed in 5 fungal sepsis (1 Candida albicans, 1 C. famata, 1 C. tropicalis, 1 C. krusei, 1 Geotrichum capitatum) 2 Aspergillosis, 2 probable fungal pneumonia cases. A favorable response was achieved in 78% of patients (4 fungemia, 2 aspergillosis, 1 probable), an unfavorable response in 1 C. krusei fungemia and in 1 probable pneumonia. Our antimicrobial pattern documented a high resistance rate to azoles. We concluded that Ambisome is an effective and well tolerated agent and its introduction has changed the outcome for many patients, although in some refractory diseases other strategies must be considered.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Drug Resistance, Fungal; Female; Fever; Humans; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Treatment Outcome

Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting.. Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study.. Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms.. L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Therapy, Combination; Female; Fluconazole; Humans; Itraconazole; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Mycoses; Myelodysplastic Syndromes; Opportunistic Infections; Prospective Studies; Survival Analysis

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

From August 1977 to October 1978, 23 patients with acute myelogenous leukemia (AML) received induction therapy at Vanderbilt University Hospital. Six patients died of documented fungal infection, predominantly aspergillus pneumonia; the complete remission rate was only 40%. Based on this experience we began using amphotericin B empirically in any AML patient remaining febrile or having recurrent fever after a week of broad spectrum antibiotics. Of 22 patients treated from October 1978 to August 1980, none died of fungal infection during induction therapy; the remission rate increased significantly to 77%. Chemotherapy and supportive care were otherwise unchanged during this period. While the first group was older, the improvement in remission rate was also seen in patients younger than 60 years of age. Since fungal infection may be difficult to document, this study suggests that empirical amphotericin B is reasonable therapy in leukemic patients remaining febrile or having a recurrent fever following a week of broad spectrum antibiotics, if the institution has a high incidence of fungal infections.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Pneumonia

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Blast Crisis; Caspofungin; Cerebrospinal Fluid; Child; Drug Therapy, Combination; Eye Infections, Fungal; Fatal Outcome; Female; Fungemia; Humans; Leukemia, Myeloid, Acute; Retinitis; Trichosporonosis; Voriconazole

Children with acute myeloid leukemia (AML) are at risk for serious electrolyte abnormalities.. We reported a case of hyperphosphatemia in a child with acute myeloid leukemia who received liposomal amphotericin B (AMBL) for the treatment of an invasive fungal infection. The findings of this case suggest that cumulative dose accumulation due to long term AMBL treatment may result in late-onset hyperphosphatemia.. This is the first case report in the literature that of late-onset hyperphosphatemia (day 56) in a patient with low-dose AMBL treatment (3-5 mg/kg/day) and normal renal function.. We highlight the importance of increasing awareness of AMBL related hyperphosphatemia among healthcare providers.

Topics: Amphotericin B; Antifungal Agents; Child; Humans; Hyperphosphatemia; Leukemia, Myeloid, Acute

The risk factors for invasive fungal infection have gradually become evident for pediatric patients with hematological diseases. Here we analyze the efficacy of liposomal amphotericin (L-AMB) for pediatric patients with febrile neutropenia using prophylactic voriconazole (VRCZ).. We administered L-AMB (2.5 mg/kg/day) in patients with febrile neutropenia who were receiving prophylactic VRCZ (10 mg/kg/day, orally) and were resistant to second-line antibiotics therapy. Thirteen patients (5 males, 8 females) with 19 febrile neutropenia episodes were targeted in this analysis. The median age of the patients was 14 years (range, 1-19 years). Eighteen out of 19 episodes occurred in patients with acute myeloid leukemia, with the remaining episode occurring in a patient with acute unclassified leukemia.. The median period from start of L-AMB administration to resolution of fever was 4 days (1-27 days). In 15 out of 19 episodes, fever resolved within 5 days from commencement of L-AMB administration. Using criteria proposed by T. J. Walsh et al., the success rate of L-AMB for febrile neutropenia was 89.5% in this study.. Although the sample size of our study was small, the extremely high efficacy of L-AMB warrants its administration in patients with febrile neutropenia who are receiving VRCZ.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Febrile Neutropenia; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Voriconazole; Young Adult

Schizophyllum commune, a basidiomycete fungus, is a quite rare cause of invasive sinusitis for which no standard treatment has yet been established. We report herein a 59-year-old woman who developed S. commune rhinosinusitis after remission induction chemotherapy for her acute myeloid leukemia. No causative microorganisms were identified in the sinus lavage fluid culture, whereas nucleotide sequencing of the internal transcribed spacer region using endoscopic sinus biopsy specimen could confirm the pathogen as S. commune. Liposomal amphotericin B and voriconazole (VRCZ) treatment ameliorated both her clinical symptoms and laboratory findings. The patient was successfully treated with allogeneic stem cell transplantation, under continuous VRCZ administration, without aggravation of S. commune sinusitis. Molecular diagnosis and prompt intervention with suitable antifungal drugs may be crucial to manage this rare infectious complication.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Leukemia, Myeloid, Acute; Middle Aged; Molecular Diagnostic Techniques; Rhinitis; Schizophyllum; Sinusitis; Transplantation, Homologous; Treatment Outcome; Voriconazole

Topics: Acetaminophen; Acidosis; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Antipyretics; Candida; Candidiasis; Child; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute; Male; Pyrrolidonecarboxylic Acid

Mucormycosis is an invasive mould that can cause aggressive infection, particularly in immunocompromised patients. Though oesophageal mucormycosis is relatively rare, it remains an elusive and devastating manifestation of this disease. The management is also challenging, due to surgical morbidity and contraindications such as thrombocytopenia in immunocompromised hosts. In this report, we present the case of a 60-year-old Lebanese man with newly diagnosed acute myeloid leukaemia who developed oesophageal mucormycosis after induction chemotherapy with idarubicin/cytarabine (7+3). The diagnosis was made when the patient developed febrile neutropenia and odynophagia. CT scan of the chest revealed a thickened oesophagus. Oesophagogastroduodenoscopy with biopsy, histopathology and PCR were performed, resulting in the diagnosis of

Topics: Amphotericin B; Antifungal Agents; Cytarabine; Esophageal Diseases; Esophagus; Humans; Idarubicin; Immunocompromised Host; Induction Chemotherapy; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Rhizopus; Triazoles

Fusarium spp. may cause invasive disseminated infections in immunocompromised patients, associated with significant morbidity and mortality. We describe a case of disseminated fusariosis with fungemia and skin localization caused by Fusarium musae in a patient with acute myeloid leukemia successfully treated using liposomal amphotericin B and voriconazole.

Topics: Amphotericin B; Antifungal Agents; Fungemia; Fusariosis; Fusarium; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Voriconazole

Appropriate use of vancomycin (VCM) is important in preventing acute kidney injury (AKI). Because of the high frequency of VCM use for febrile neutropenia and concomitant use of other nephrotoxic drugs, haematologic patients have a different nephrotoxic background compared with patients with other diseases. Therefore, it is unclear whether the risk factors of VCM-induced AKI identified in other patient groups are also applicable to haematologic patients. Herein, we performed a single-centre retrospective analysis to identify the factors associated with VCM-induced AKI in haematologic patients.. We retrospectively analysed 150 haematologic patients to whom VCM was administered between April 2010 and March 2018 at Tokushima University Hospital. VCM-induced AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analyses were performed to identify risk factors for VCM-induced AKI.. Seventeen patients had VCM-induced AKI. Multivariate analysis revealed that the risk factors of VCM-induced AKI were an initial VCM trough concentration of > 15 mg/L and concomitant use of tazobactam/piperacillin (TAZ/PIPC) and liposomal amphotericin B (L-AMB). Patients with an initial VCM trough concentration of < 10 mg/L showed significantly lower efficacy in febrile neutropenia. Interestingly, concomitant L-AMB use increased the incidence of VCM-induced AKI in a VCM concentration-dependent manner, whereas concomitant TAZ/PIPC increased the incidence in a VCM concentration-independent manner.. The optimal initial VCM trough concentration was 10-15 mg/L in haematologic patients, considering safety and effectiveness. There were differences in the effect of VCM-induced AKI between nephrotoxic drugs.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Drug Interactions; Female; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Middle Aged; Multiple Myeloma; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Surveys and Questionnaires; Vancomycin

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient's condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Female; Hepatolenticular Degeneration; Humans; Leukemia, Myeloid, Acute; Liver Transplantation; Middle Aged; Mucormycosis; Postoperative Complications

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Artifacts; Biomarkers; Blood Chemical Analysis; Child; False Positive Reactions; Female; Humans; Hyperphosphatemia; Leukemia, Myeloid, Acute; Phosphates; Predictive Value of Tests; Pulmonary Aspergillosis

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Biopsy; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid, Acute; Middle Aged; Skin; Treatment Failure; Trichosporon; Trichosporonosis

Opportunistic infections frequently develop in immunocompromised patients, such as those with hematological malignancies, causing significant mortality. Early diagnosis of invasive fungal infections is often important and difficult due to the difficult nature of confirming infection using cytologic and histologic findings. However, we report the first case of candidal infection leading to muscle abscesses in the legs of a patient with leukemia.. A 60-year-old man with acute myeloid leukemia (AML) presented with multifocal muscle abscesses of the legs.. Multifocal muscle candidiasis of the legs was confirmed by fine-needle aspiration biopsy of 2 of the calf lesions.. After treatment with amphotericin B and flucytosine for 1 month, the patient was administered intravenous caspofungin for 3 months.. A CT scan of the abdomen and an MRI of the lower calves showed significant improvement.. This case highlights that fungal infection should be considered when patients present with multiple abscesses, emphasizing the value of early biopsy to confirm diagnosis and facilitate precision treatment.

Topics: Abscess; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida tropicalis; Candidiasis; Caspofungin; Flucytosine; Humans; Immunocompromised Host; Leg; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Opportunistic Infections; Tomography, X-Ray Computed

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

Endophthalmitis is a rare infection of the vitreous and/or aqueous. It can be bacterial or fungal. Exogenous endophthalmitis is the most common form and results from direct inoculation of a pathogen after eye surgery or penetrating trauma. Endophthalmitis can also be endogenous, secondary to disseminated infection. Fungal endophthalmitis is associated with poor prognosis and treatment is difficult given the low penetration of most of the antifungal agents available and the emergence of resistant filamentous fungi like Fusarium. To our knowledge, we describe the first endogenous fungal endophthalmitis due to Fusarium dimerum, a ubiquitous pathogen found in soil and plants. A 71-year-old woman, diagnosed with acute myeloid leukemia, was hospitalized for surveillance after induction chemotherapy. Prophylaxis by antibiotics and posaconazole was ongoing when she complained of pain and decreased vision in the left eye. A voluminous chorioretinal abscess developed and after multiple sterile aqueous humour samples, only vitrectomy allowed diagnosis with fungal hyphae seen on May-Grünwald Giemsa stained smear and positive cultures. The fungus was identified as Fusarium dimerum. The treatment, that included intravitreal injections of voriconazole and amphotericin B associated with systemic administration of voriconazole, allowed complete control of the infection. The source of this infection could not be confirmed despite the discovery of several possible infection sites including a periungual whitlow on the left hand and a lesion on a nail, from which samples were negative in microbiology laboratories. Unfortunately, damages of the retina were too important and the patient did not recover sight of her left eye.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Endophthalmitis; Eye; Female; Fusarium; Humans; Hyphae; Immunocompromised Host; Leukemia, Myeloid, Acute; Treatment Outcome; Triazoles; Vitrectomy; Voriconazole

Topics: Aged; Amphotericin B; Antifungal Agents; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases; Male; Mucormycosis; Nose Diseases; Pancytopenia; Treatment Outcome; Triazoles

We herein report a rare case of oral mucormycosis following allogeneic hematopoietic stem cell transplantation. Oral mucormycosis due to Rhizopus microsporus manifested as localized left buccal mucositis with a 1-cm black focus before neutrophil recovery. Combination therapy with liposomal amphotericin B was initiated and surgical debridement was performed; however, the patient died due to progressive generalized mucormycosis. Considerable attention needs to be paid to the diagnosis and management of oral mucormycosis in post-transplant patients, thereby suggesting the importance of fully understanding the risk factors.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Debridement; Fatal Outcome; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Rhizopus; Risk Factors; Stomatitis

We present a case of a 61-year-old Caucasian woman who was hospitalized with fever on day 176 after a matched unrelated stem cell transplant for acute myelogenous leukemia. She developed hemorrhagic bullae on the skin of her right thigh, and both blood cultures and skin biopsy confirmed Fusarium proliferatum. Despite antifungal therapy, her condition worsened and she died while on comfort-only measures.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Female; Fusariosis; Fusarium; Humans; Leukemia, Myeloid, Acute; Middle Aged; Stem Cell Transplantation

Patients with hematologic malignancies as well as allogeneic hematopoietic stem cell transplantation (HSCT) patients are at high risk for invasive aspergillosis. Here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an allogeneic HSTC patient which he developed despite posaconazole prophylaxis. The agent was determined to be an azole-resistant

Topics: Aged; Alleles; Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Azoles; Caspofungin; Cytochrome P-450 Enzyme System; Drug Resistance, Multiple, Fungal; Echinocandins; Fungal Proteins; Humans; Invasive Pulmonary Aspergillosis; Leukemia, Myeloid, Acute; Lipopeptides; Male; Microbial Sensitivity Tests; Mutation; Treatment Outcome; Triazoles; Voriconazole

We present the case of a 51-year-old man with acute myeloid leukemia who developed fevers with a skin lesion following the first cycle of induction chemotherapy. Skin biopsy showed evidence of invasive fungal infection. Cultures remained negative, but polymerase chain reaction on tissue detected Rhizopus oryzae complex. The patient was started on liposomal amphotericin B and underwent surgical debridement. He was switched to posaconazole, with plans for allogeneic hematopoetic stem cell transplant in the future.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Biopsy; Debridement; Dermatomycoses; Febrile Neutropenia; Forearm; Humans; Immunocompromised Host; Induction Chemotherapy; Invasive Fungal Infections; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Polymerase Chain Reaction; Rhizopus; RNA, Fungal; Triazoles

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Topics: Acute Disease; Acyclovir; Amphotericin B; Antifungal Agents; Appendicitis; Aspergillosis; Aspergillus; Child; Ciprofloxacin; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Voriconazole

Acute myeloid leukemia (AML) is a clonal hematopoietic disorder resulting from genetic alterations in normal hematopoietic stem cells. The aim of this study was to evaluate prognostic factors and survival of AML patients in the Northeast of Iran.. This retrospective study covered 96 patients with AML referred to Emam Reza Hospital, Mashhad city, Iran, from 2009 to 2015. Age, sex, blood group, type of AML, fever, consumption of amphotericin B, cytogenetic forms and survival were analyzed. Also, WBC, hemoglobin and platelet levels were checked. Mean follow-up was 30.5 months (60.4% mortality). Survival was plotted by GraphPad Prism 5 with Log-rank test.. The mean age for all AML patients at diagnosis was 40.4 years (range, 17-77 years). Some 42.7% patients were aged <35 years and 40.6% were male. In all patients, 76% had fever and 50% consumed amphotericin. T(15;17)(q22;q21) had the most prevalence (37.7%) compared to other forms. Out of 92 patients, O+(30.4%) was the most common blood group and AML-M5 (28.3%) the most common subtype. There was a significant difference in survival based on WBC and consumption of amphotericin B (P<0.05).. WBC level, fever and consumption of amphotericin B proved to be factors for survival of AML patients. The mean age for patients in Iran is lower than other areas in the World and also survival in this study was higher than in other studies.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Female; Follow-Up Studies; Humans; Iran; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Young Adult

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fusariosis; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Treatment Outcome; Voriconazole; Young Adult

Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) is a devastating early or late complication of treatment for childhood cancer related with a significant morbidity and mortality. We retrospectively studied survivors of childhood cancer. Overall, 287 patients were recorded in the databases and we identified three (1.04%) with t-MDS. The primary cancer diagnoses were Langerhans cell histiocytosis (one patient) and acute lymphoblastic leukemia (ALL; two patients). The mean age of patients was 12.1 years. All patients had received systemic antifungal treatment for invasive pulmonary aspergillosis successfully treated with voriconazole and liposomal amphotericin B before diagnosis of t-MDS. Two patients (66%) remain alive after a median follow-up period of 3.5 years.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Humans; Leukemia, Myeloid, Acute; Male; Myelodysplastic Syndromes; Neoplasms, Second Primary; Retrospective Studies; Voriconazole

Chemotherapy-induced neutropenia can be complicated by invasive pulmonary aspergillosis (IPA). In 2008, liposomal amphotericin B (L-AmB) inhalation was shown to prevent IPA in a placebo-controlled trial. Patients with acute myeloid leukaemia (AML) are the subset of haematology patients at high risk for IPA. In 2008, L-AmB inhalation prophylaxis became the standard of care for all AML patients in Erasmus MC. In this study, the efficacy and cost effectiveness of L-AmB inhalation were evaluated in a prospective cohort of AML patients. In total, 127 consecutive AML patients received chemotherapy and prophylactically inhaled L-AmB during their first and second chemotherapy cycles; 108 patients treated for AML at the same sites from 2005-2008 served as controls. A standardised diagnostic protocol was used and probable/proven IPA served as the primary endpoint. Diagnostic and therapeutic costs were also comprehensively analysed and compared. A significant decrease in probable/proven IPA in the L-AmB inhalation group was observed (L-AmB 9.5% vs. controls 23.4%; P=0.0064). Systemic antifungal therapy given at any time during the entire AML therapy decreased from 52.8% to 29.9%. Per-patient equipment and drug costs for L-AmB inhalation (1292 €/patient) were more than compensated for by a decrease in costs for diagnostics and therapeutic voriconazole use (-1816 €/patient). No serious adverse events related to L-AmB inhalation were observed. In an unselected AML patient group, L-AmB inhalation resulted in a significant and substantial decrease in IPA and was cost saving. Now that azole resistance is more frequent, non-azole-based prophylaxis may become an attractive strategy.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Chemoprevention; Cost-Benefit Analysis; Diagnostic Tests, Routine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Netherlands; Prospective Studies; Treatment Outcome; Young Adult

Pregnant women should be managed by a multidisciplinary team that includes haematologists, obstetricians, neonatologists and anaesthetists (Grade 1C) As for non-pregnant patients, acute myeloid leukaemia (AML) should be diagnosed using the World Health Organization (WHO) classification (Grade 1A) Women diagnosed with AML in pregnancy should be treated without delay (Grade 1B) When the diagnosis of AML is made in the first trimester, a successful pregnancy outcome is unlikely and spontaneous pregnancy loss in this situation carries considerable risks for the mother. The reasons for and against elective termination should be discussed with the patient (Grade 2C) In the case of presentation beyond 32 weeks gestation, it may be reasonable to deliver the foetus prior to commencement of chemotherapy (Grade 2C) Between 24 and 32 weeks, risks of foetal chemotherapy exposure must be balanced against risks of prematurity following elective delivery at that stage of gestation (Grade 1C) The risk-benefit ratio must be carefully considered before using any drugs in pregnancy (Grade 1C) Where AML induction chemotherapy is delivered, a standard daunorubicin, cytarabine 3 + 10 schedule should be used (Grade 1B) Chemotherapy should be dosed according to actual body weight and adjustments made for weight changes during treatment (Grade 1C) Quinolones, tetracyclines and sulphonamide use should be avoided in pregnancy (Grade 1B) Amphotericin B or lipid derivatives are the antifungal of choice in pregnancy (Grade 2C) Cytomegalovirus (CMV)-negative blood products should be administered during pregnancy regardless of CMV serostatus (Grade 1B) A course of corticosteroids should be considered if delivery is anticipated between 24 and 35 weeks gestation, given over a 48-h period during the week prior to delivery (Grade 1A) Use of magnesium sulphate should be considered in the 24 h prior to delivery if this is before 30 weeks gestation (Grade 1A) Where possible, delivery should be planned for a time when the woman is at least 3 weeks post-chemotherapy to minimize risk of neonatal myelosuppression (Grade 1C) Planned delivery is easier to manage than spontaneous labour; induction of labour is usually advised (Grade 2C) Epidural analgesia should be avoided in a woman who is significantly thrombocytopenic (platelet count <80 × 10(9) /l) and/or neutropenic (white blood cell count <1 × 10(9) /l): (Grade 1C) Elective caesarean section should only be recommended for obstetric indications (

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Delivery, Obstetric; Female; Humans; Leukemia, Myeloid, Acute; Pregnancy; Pregnancy Complications, Neoplastic

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Drug Resistance, Fungal; Fatal Outcome; Female; Fever; Fusariosis; Fusarium; Humans; Idarubicin; Leukemia, Myeloid, Acute; Triazoles; Young Adult

Topics: Amphotericin B; Antifungal Agents; Biopsy, Fine-Needle; Humans; Image-Guided Biopsy; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Multiple Pulmonary Nodules; Tomography, X-Ray Computed; Treatment Outcome; Triazoles

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

Zygomycosis is a lethal and invasive mold infection that is often associated with hematological malignancies. The keys for successful treatment include making a rapid diagnosis and appropriately administering antifungal agents. We herein report the early diagnosis of a case of zygomycosis in a patient with acute myeloid leukemia using a deoxyribonucleic acid sequence analysis. We successfully performed allogeneic hematopoietic stem cell transplantation with the use of high-dose liposomal amphotericin B and granulocyte transfusion.

Topics: Amphotericin B; Antifungal Agents; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Polymerase Chain Reaction; Rhizomucor; Sequence Analysis, DNA

Topics: Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Humans; Leukemia, Myeloid, Acute; Mucormycosis; Skin Diseases; Treatment Outcome

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biomarkers; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Micafungin; Multiple Organ Failure; Scedosporium; Treatment Failure

We report a 38-year-old woman presenting with febrile neutropenia, acute myeloid leukemia (AML) and invasive mucormycosis. Bone marrow aspirate was characteristic of AML minimally differentiated (WHO classification 2008). Flow cytometric immunophenotyping analysis showed blasts positive for CD7, CD33, CD34, CD71, CD117, HLA-DR, MPO, and TdT, with normal karyotype (46, XX), and the absence of the FLT3-ITD and NPM1 mutations. The patient's management included chemotherapy with cytarabine and idarubicin, and treatment with liposomal amphotericin B, deferasirox, hyperbaric oxygen therapy, and antibiotics. Nowadays, she is in complete hematological remission, and CT images of control are normal. Invasive mucormycosis is an uncommon and severe condition, which involves diagnosis and treatment challenges. Clinical features and predisposing factors should be highlighted in order to enhance the suspicion index, contributing to early diagnosis and disease control. Our aim is to report classical features of this uncommon condition and to emphasize usual management challenges.

Topics: Adult; Amphotericin B; Antifungal Agents; Benzoates; Bone Marrow; Deferasirox; Drug Therapy, Combination; Female; Humans; Hyperbaric Oxygenation; Immunophenotyping; Karyotyping; Leukemia, Myeloid, Acute; Mucormycosis; Nucleophosmin; Treatment Outcome; Triazoles

Topics: Adult; Amphotericin B; Antifungal Agents; Azoles; Communicable Diseases, Emerging; Fatal Outcome; Febrile Neutropenia; Humans; Induction Chemotherapy; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Pyrimidines; Respiratory Distress Syndrome; Tomography, X-Ray Computed; Triazoles; Voriconazole

Topics: Amphotericin B; Aneurysm, Infected; Antifungal Agents; Female; Fusariosis; Humans; Immune Reconstitution Inflammatory Syndrome; Immunocompromised Host; Leukemia, Myeloid, Acute; Middle Aged; Pyrimidines; Triazoles; Voriconazole

We report a case of mycotic pneumonia in a patient with acute myeloblastic leukemia. Rhizopus microsporus was identified as an agent of mucormycosis and proven by microscopy and culture. The determination of the isolate was supported by molecular methods. Combined treatment with surgery (right-sided pneumonectomy) and systemic amphotericin B and posaconazole antifungal therapy was chosen. In this case, amphotericin B Neo-Sensitabs tablets gave false "resistant" results on Mueller-Hinton agar when using the disk diffusion test. There was a good correlation between the Etest (16 h) and the Sensititre YeastOne microplate (24 h) for amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Mucormycosis; Rhizopus

Fusarium species are among the leading fungal pathogens to cause invasive mould infections in patients with hematopoietic malignancy. The Fusarium species most frequently involved in human infections are Fusarium solani, Fusarium oxysporum and Fusarium verticillioides. However, identification is a cumbersome and time-consuming task. Fusarium is resistant in vitro to many of the antifungal agents and the management of fusariosis is not well defined.. To emphasise the difficulty of identifying Fusarium spp. by conventional methods and the need of new rapid molecular tests to achieve earlier diagnosis and appropriate therapy.. A disseminated Fusarium infection due to F. verticillioides was documented in a neutropenic refractory patient with acute myeloid leukaemia, relapsed after allogeneic hematopoietic stem cell transplantation.. The patient died despite liposomal amphotericin B and voriconazole combination and "in vitro" susceptibility of agents employed. Morphological and molecular identification of F. verticillioides was obtained only after the death of the patient.. This case highlights the poor outcome of an invasive fungal disease caused by Fusarium in aplastic patients. Identification of members of Fusarium genus remains restricted to selected laboratories and should be introduced into routine mycological diagnostics. In immunocompromised patients, diagnosis of fusariosis is directly related to prompt diagnosis and to patient's status. Current diagnosis methods and therapeutic options are discussed.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Drug Resistance, Multiple, Fungal; Etoposide; Fatal Outcome; Female; Fusariosis; Fusarium; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid, Acute; Mitoxantrone; Neutropenia; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Premedication; Pyrimidines; Recurrence; Salvage Therapy; Transplantation, Homologous; Triazoles; Voriconazole

Mucormycosis has emerged as an increasingly important infection in oncology centres with high mortality, especially in severely immunocompromised patients. We carried out a retrospective study of 11 children with mucormycosis treated in seven French oncology-haematology paediatric wards during the period from 1991 to 2011. Lichtheimia corymbifera and Mucor spp. were the predominant pathogens. Treatment regimens included antifungal therapy, reversal of underlying predisposing risk factors and surgical debridement. Although mucormycosis is associated with high mortality, this infection could be cured in eight of our cases of severely immunocompromised paediatric cancer patients.

Topics: Adolescent; Amphotericin B; Antineoplastic Agents; Child; Female; Hospitals, Pediatric; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Mucor; Mucormycosis; Neutropenia; Opportunistic Infections; Retrospective Studies; Risk Factors; Young Adult

Topics: Amphotericin B; Antiprotozoal Agents; Cord Blood Stem Cell Transplantation; Duodenal Diseases; Fatal Outcome; Female; Humans; Leishmaniasis; Leukemia, Myeloid, Acute; Middle Aged; Transplantation, Homologous

Topics: Aged; Amphotericin B; Antifungal Agents; Drug Resistance, Fungal; Fusariosis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Pyrimidines; Triazoles; Voriconazole

To describe changes in costs of managing hospitalised patients with acute myeloid leukaemia (AML) after chemotherapy in Germany over 3 yr, with a special focus on prophylaxis and treatment patterns as well as resource use related to invasive fungal infections (IFI).. The study was conducted as a retrospective, single-centre chart review in patients with AML hospitalised for chemotherapy, neutropenia and infections after myelosuppressive chemotherapy from January 2004 to December 2006 in Germany. The following resource utilisation data were collected: inpatient stay, mechanical ventilation, parenteral feeding, diagnostics, systemic antifungal medication and cost-intensive concomitant medication. Direct medical costs were calculated from hospital provider perspective.. A total of 471 episodes in 212 patients were included in the analysis. Occurrence of IFI decreased from 5.9% in 2004 to 1.9% in 2006. Mean (± standard deviation) hospital stay decreased from 28.7 ± 17.9 d in 2004 to 22.4 ± 11.8 d in 2006. From 2004 to 2006, the use of a single antifungal drug increased from 30.4% to 46.9%, whereas the use of multiple antifungal drugs decreased from 24.4% to 13.1%. The use of liposomal amphotericin B declined between 2004 and 2006 (21.4% vs. 3.8%) and caspofungin between 2005 and 2006 (19.3% vs. 8.1%). Total costs per episode declined from €19051 ± 19024 in 2004 to €13531 ± 9260 in 2006; major reductions were observed in the use of antimycotics and blood products as well as length of hospital stay.. Analysis of real-life data from one single centre in Germany demonstrated a change in antifungal management of patients with AML between 2004/2005 and 2006, accompanied by a decline in total costs.

Topics: Aged; Amphotericin B; Antifungal Agents; Caspofungin; Costs and Cost Analysis; Echinocandins; Female; Germany; Hospitals; Humans; Length of Stay; Leukemia, Myeloid, Acute; Lipopeptides; Male; Middle Aged; Parenteral Nutrition; Respiration, Artificial; Retrospective Studies

Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Drug Therapy, Combination; Fatal Outcome; Fungemia; Humans; Leukemia, Myeloid, Acute; Male; Pyrimidines; Triazoles; Trichosporon; Trichosporonosis; Voriconazole; Young Adult

Blastoschizomyces capitatus is a rare fungal pathogen that may lead to fatal infections especially in immunosuppressive individuals. In this report, three cases of B.capitatus were presented. The patients were under treatment for acute myeloid leukemia and their blood cultures yielded B.capitatus. The patients clinical conditions deteriorated and they died despite amphotericin B treatment. The isolates were identified by conventional mycological methods and API 20C AUX (Bio-Mérieux, France) system. Antifungal susceptibility test of the strains was performed with Sensititre Yeast One Panel (Trek Diagnostic Systems, USA) and minimum inhibitory concentration (MIC) ranges for amphotericin B, caspofungin, fluconazole, itraconazole, voriconazole, posaconazole, and flucytosine were found as 0.5-1; > 16; 8-16; 0.5; 0.25; 0.5-1 and 0.06-0.25 µg/ml, respectively. Isolated strains were genotyped with RAPD-PCR (Random Amplified Polymorphic DNA-Polymerase Chain Reaction) using Cnd-3, Cnd-4, OPE-03, OPE-18 primers. The strains isolated from the first two cases were found to be genotypically identical, while the strain isolated from the third case was different. Genotypically identical isolates belonged to two patients who were admitted to the hospital with approximately 18 months interval. The other strain with a unique genotype, was isolated from a patient who was admitted to the hospital about two years later than the other two patients. In conclusion, B.capitatus should be considered as an important opportunistic pathogen especially in patients with hematologic malignancies. The data of this study demonstrated that the lowest MIC values for B.capitatus strains were with voriconazole.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Female; Fungemia; Genotype; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Random Amplified Polymorphic DNA Technique; Saccharomycetales

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials. In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA. In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting.

Topics: Administration, Oral; Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Invasive Pulmonary Aspergillosis; Leukemia, Myeloid, Acute; Male; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Pyrimidines; Retrospective Studies; Survival Rate; Triazoles; Voriconazole

We report the first culture-proven case of invasive aspergillosis (IA) caused by azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia in Germany. IA presented as breakthrough infection under posaconazole prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation in the cyp51A gene, which indicates an environmental origin of the strain. This case underscores the need for monitoring azole resistance in Aspergillus spp. and for routine susceptibility testing of moulds.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Azoles; Cytochrome P-450 Enzyme System; Drug Resistance, Fungal; Fever; Fungal Proteins; Germany; Humans; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Mutation; Polymerase Chain Reaction; Pyrimidines; Sequence Analysis; Treatment Outcome; Triazoles; Voriconazole

Mucormycosis is a serious invasive fungal infection in immunocompromised patients. Patients undergoing treatment for hematologic malignancies are predominantly prone to the pulmonary manifestation of mucormycosis. Historically, allogeneic hematopoietic cell transplantation (HCT) in patients suffering from pulmonary mucormycosis (PM) was considered contraindicated owing to mortality rates up to 90%. We present 3 patients with acute myeloid leukemia and PM who were treated with radical surgical debridement combined with high-dose liposomal amphotericin B (LAB), and subsequently underwent successful allogeneic HCT. To date, all 3 patients are in complete remission and show no signs of mucormycosis. Allogeneic HCT in patients with PM seems feasible provided that the infectious focus is completely removed surgically and adequate antifungal pharmacotherapy, such as high-dose LAB or posaconazole, is established.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Transplantation, Homologous

Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in patients who undergo haematopoietic stem cell transplantation (HSCT). History of IA before allogeneic HSCT is still challenging because of the high risk of recurrence after HSCT. Recent advances in early-stage diagnosis and new, more effective classes of antifungal agents have improved the management of IA in the HSCT recipients. We report two cases with acute myelogenous leukaemia after primary failure of induction chemotherapy with the patients developing pulmonary IA. They responded well to a combination of voriconazole (VCZ) and micafungin, resulting in a remarkable reduction of pulmonary IA lesions at short intervals. Thereafter, antifungal therapy was switched to liposomal amphotericin B (L-AmB), followed by conditioning regimen for allogeneic HSCT, because of the possibility of VCZ altering the metabolism of chemotherapeutic agents and calcineurin inhibitors. Successful engraftment was achieved without severe adverse side-effects or aggravation of IA after HSCT. Combining VCZ with micafungin followed by L-AmB throughout HSCT could be advantageous in stabilising IA in HSCT patients.

Topics: Amphotericin B; Antifungal Agents; Echinocandins; Female; Humans; Invasive Pulmonary Aspergillosis; Leukemia, Myeloid, Acute; Lipopeptides; Micafungin; Middle Aged; Pyrimidines; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome; Triazoles; Voriconazole

Topics: Adult; Amphotericin B; Antifungal Agents; Dipodascus; Female; Humans; Leukemia, Myeloid, Acute; Liver; Middle Aged; Mycoses; Portal Vein; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography, Abdominal; Tomography, X-Ray Computed; Treatment Outcome

Therapy-related acute myelogenous leukemia (t-AML) is a generally fatal disease with a very poor response to conventional chemotherapy. Allogeneic stem cell transplantation (allo-SCT) has been reported in patients with chemotherapy- responsive t-AML. However its use is limited owing to complications from previous treatments. Nonmyeloablative conditioning provides rapid hematologic engraftment and it is a feasible option for patients who are at increased risk for conventional SCT. There are few data on their use in patients with t-AML. We describe the case of a boy who developed visceral fungal infection with liver abscesses after induction chemotherapy for t-AML. He received allo-SCT with a nonmyeloablative regimen, plus amphotericin B during the transplant procedure. The patient is alive and free of both leukemia and fungal infection 2 years after allo-SCT. Nonmyeloablative allo-SCT may provide durable remission in patients with t-AML, preexisting invasive fungal infections, and a high risk of adverse effects from standard chemotherapy and prolonged cytopenia, without resurgence of the fungal infection.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Child; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Transplantation, Homologous; Treatment Outcome

This study aimed to determine the frequency of invasive fungal infection (IFI) in pediatric patients with hematologic malignancy who received amphotericin B oral suspension and early intravenous fluconazole during the neutropenic phase as prophylaxis for IFI. Records of 743 neutropenic episodes induced by cytotoxic chemotherapy between 1997 and 2008 were retrospectively reviewed to determine risk factors for and frequency of IFI. The overall frequency of IFI was 0.8% (n=6) and frequencies of proven, probable, and possible infections were 0.3% (n=2), 0.4% (n=3), and 0.1% (n=1), respectively. During 351 episodes of profound neutropenia (neutrophil count <500/μL for ≥ 14 d), overall incidence of IFI was 1.71% (n=6). Pulmonary aspergillosis was the most common causative agent, and no patients showed candidemia, or hepatosplenic candidiasis. Cytotoxic chemotherapy regimens for acute myelogenous leukemia and profound neutropenia were significantly associated with IFI (P=0.004 and P=0.009, respectively). No IFI-attributable deaths or breakthrough fungal infections occurred. Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies.

Topics: Administration, Oral; Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Female; Fluconazole; Humans; Incidence; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Neutropenia; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Adult; Amphotericin B; Humans; Leukemia, Myeloid, Acute; Liposomes; Lung Diseases, Fungal; Treatment Outcome

The aim of this study was to evaluate prognostic factors, treatments and outcome of invasive aspergillosis in patients with acute myeloid leukemia based on data collected in a registry.. The registry, which was activated in 2004 and closed in 2007, collected data on patients with acute myeloid leukemia, admitted to 21 hematologic divisions in tertiary care centers or university hospitals in Italy, who developed proven or probable invasive aspergillosis.. One hundred and forty cases of invasive aspergillosis were collected, with most cases occurring during the period of post-induction aplasia, the highest risk phase in acute myeloid leukemia. The mortality rate attributable to invasive aspergillosis was 27%, confirming previous reports of a downward trend in this rate. Univariate and multivariate analyses revealed that the stage of acute myeloid leukemia and the duration of, and recovery from, neutropenia were independent prognostic factors. We analyzed outcomes after treatment with the three most frequently used drugs (liposomal amphotericin B, caspofungin, voriconazole). No differences emerged in survival at day 120 or in the overall response rate which was 71%, ranging from 61% with caspofungin to 84% with voriconazole.. Our series confirms the downward trend in mortality rates reported in previous series, with all new drugs providing similar survival and response rates. Recovery from neutropenia and disease stage are crucial prognostic factors. Efficacious antifungal drugs bridge the period of maximum risk due to poor hematologic and immunological reconstitution.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Caspofungin; Echinocandins; Female; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Male; Middle Aged; Prospective Studies; Pyrimidines; Registries; Survival Rate; Treatment Outcome; Triazoles; Voriconazole; Young Adult

Topics: Adolescent; Alternaria; Amphotericin B; Antifungal Agents; Child, Preschool; Female; Humans; Leukemia, Myeloid, Acute; Male; Mycoses; Pyrimidines; Sinusitis; Triazoles; Voriconazole

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Digestive System Surgical Procedures; Enterococcus faecium; Fatal Outcome; Female; Gram-Positive Bacterial Infections; Humans; Idarubicin; Leukemia, Myeloid, Acute; Middle Aged; Mucormycosis; Neutropenia; Rhinitis; Shock, Septic; Sinusitis; Typhlitis

Invasive Zygomycetes infection complicating prolonged neutropenia is associated with high mortality in the absence of immune recovery. We report a patient who developed disseminated zygomycosis due to Rhizopus microsporus during induction chemotherapy for acute myeloid leukemia. Rescue allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed as her only chance of cure of this infection and to treat refractory leukemia. Posaconazole combined with liposomal amphotericin B contained the zygomycosis during prolonged neutropenia due to allo-HSCT followed by intense immunosuppression for grade IV acute graft-versus-host disease. Surgical removal of all infected sites after immune recovery, with prolonged posaconazole treatment, ultimately cured the infection. New combination antifungal therapies might sufficiently control disseminated zygomycosis to allow allo-HSCT to be performed, assuring life-saving immune recovery. Surgery appears to be necessary for definite cure of these infections.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mucormycosis; Rhizopus; Salvage Therapy; Transplantation, Homologous; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antifungal Agents; Cord Blood Stem Cell Transplantation; Female; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mucormycosis; Treatment Outcome

During the past two decades, an increasing number of unusual moulds has been reported as responsible for septicaemia and systemic or disseminated infections in immunocompromised patients. Investigation of fever in a 10-year-old boy with acute myeloblastic leukaemia, including blood cultures on selective media, allowed the diagnosis of a fungaemia due to the slow-growing fungus Acremonium strictum. The patient recovered with liposomal amphotericin B (AmB) and voriconazole, followed by voriconazole alone due to AmB resistance. Facing a neutropenic patient with fever, clinicians usually suspect bacterial or viral aetiologies. This case, however, illustrates the need for mycological analysis of blood samples in febrile neutropenic patients and for antifungal susceptibility testing.

Topics: Acremonium; Amphotericin B; Antifungal Agents; Blood; Child; Fever; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Triazoles; Voriconazole

A retrospective study was performed to evaluate the efficacy and safety of liposomal amphotericin B (L-AMB) in a total of 32 cases who were among patients hospitalized at the Fourth Department of Internal Medicine, Sapooro Medical University from December 2006 to April 2008. Primary diagnoses were hematologic diseases in 87.5% of subjects. The most common hematologic diseases included acute myelogenous leukemia in 50% of the subjects, followed by malignant lymphoma in 12.5% of the subjects. The mean administration period was 14.2 +/- 12.9 days, and the mean cumulative dose was 1,786 +/- 2,181 mg. L-AMB improved 21 of 29 cases (72.4%) with some fungal infections or fever-associated neutropenia. Adverse events occurred in 9 cases to a slight degree, in 7 cases to a moderate degree, and in no case to a severe degree. Hypokalemia and hypercreatininemia were seen in 7 cases (21.9%) and 4 cases (12.5%), respectively, but these adverse reactions were so mild that the treatment did not need to be discontinued. Any adverse reactions for which treatment administration was discontinued were confirmed to have disappeared at the end of the study. These results support the efficacy and safety of L-AMB in accordance with previous foreign reports. It was noteworthy that early use of L-AMB prior to established diagnosis sometimes better therapeutic outcomes. It was also suggested that L-AMB could be safely administered while controlling electrolyte balance, such as serum potassium concentration, with sufficient fluid replacement, including physiological saline infusion. There are limitations in the use of the conventional form of amphotericin B because of its renal toxicity and other reasons. However, L-AMB had fewer side effects, so the agent was considered useful for the treatment of hematologic disease patients who either had mycosis or carried a risk for fungal infection.

Topics: Amphotericin B; Female; Humans; Leukemia, Myeloid, Acute; Liposomes; Lymphoma; Male; Retrospective Studies

In order to assess physicians' compliance with international guidelines for the targeted treatment of invasive aspergillosis, 136 patients with acute myeloid leukaemia and proven/probable invasive aspergillosis were analysed.. Compliance with Infectious Diseases Society of America (IDSA) and European Conference on Infections in Leukaemia (ECIL) guidelines was found to be relatively low (28% for ECIL and 55% for IDSA), although no significant differences were found between the two groups (adherence versus non-adherence). In both subgroup analyses (IDSA and ECIL), compliance with the guidelines did not impact the 120 day survival rate. Instead, adherence to guidelines led to a higher response rate to first-line antifungal treatment (76% in the IDSA group and 84% in the ECIL group).. Guidelines establish categories of patients with homogeneous characteristics, and suggest optimal diagnostic and therapeutic options for them. Acquisition of good results through adherence to guidelines is confirmed by our series. Unfortunately, there are frequently reasons to deviate from these general recommendations, particularly in patients with acute myeloid leukaemia. Despite evidence-based recommendations, adherence to the guidelines does not constitute the best therapeutic choice in each and every patient. Subjects' clinical conditions and co-morbidities vary widely, and sometimes render the 'recommended' drug a non-applicable strategy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Echinocandins; Guideline Adherence; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Pyrimidines; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole

A rare case of oromandibular Rhizopus oryzae infection is described in a 55-year-old woman with acute myeloid leukaemia and decompensated diabetes mellitus. The infection developed during induction chemotherapy when the patient was neutropenic. She was treated with a combination of amphotericin B lipid formulation and caspofungin plus surgery. Debridement surgery included excision of the lower lip, chin, floor of the mouth, a portion of the tongue, as well as mandibular resection at the level of the horizontal branches. Eight weeks of combined antifungal therapy were followed by secondary prophylaxis with amphotericin B lipid formulation during consolidation chemotherapy after achieving complete response of both leukaemia and mucormycosis. Reconstructive surgery was carried out including insertion of a new biomaterial porous mandibular prosthesis, which showed excellent functionality after long-term follow-up, followed by several plastic surgery procedures once good tolerability and no adverse effects of the prosthesis were observed. This case shows that a well-coordinated multidisciplinary approach is critical to increase the chances of clinical success in this life-threatening infection.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Chin; Drug Therapy, Combination; Echinocandins; Female; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Mandible; Middle Aged; Mouth; Mucormycosis; Necrosis; Plastic Surgery Procedures

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

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

An eleven-year-old boy presented with one month's history of fever and weight loss. He was diagnosed with Acute Mycloid Leukemia (AML-M2). During treatment he developed recurrent infections with neutropenia requiring prolonged antibiotics and subsequently developed invasive aspergillosis. He was treated with amphotericin B and Voriconazole. This case shows the efficacy and safety of combined antifungal therapy, including voriconazole, for invasive aspergillosis complicating AML.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Child; Fever; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

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

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Bronchoscopy; Fatal Outcome; Humans; Leukemia, Myeloid, Acute; Lung; Lung Diseases, Fungal; Male; Pyrimidines; Tomography, X-Ray Computed; Triazoles; Voriconazole; Young Adult; Zygomycosis

A 37-year-old woman, during her second remission of acute myeloid leukemia, presented with severe neck pain and cervico-brachial neuralgia. Investigation revealed a C5-C6 spondylodiscitis. A CT-guided anterior biopsy decompressed the mass, immediately alleviated the symptoms, and isolated a rare yeast: Blastoschizomyces capitatus. To our knowledge, only three cases of spondylodiscitis with this yeast have been described. Six months of voriconazole and liposomal amphotericin B treatment produced a complete resolution on CT and MRI imaging. However, the ongoing severe yeast infection prevented the planned bone marrow allograft.

Topics: Adult; Amphotericin B; Antifungal Agents; Cervical Vertebrae; Dipodascus; Discitis; Female; Humans; Leukemia, Myeloid, Acute; Mycoses; Neck; Pyrimidines; Tomography, X-Ray Computed; Triazoles; Ultrasonography; Voriconazole

Here we describe a rare case of pulmonary mucormycosis and simultaneous cervical lymphadenitis in a patient with acute myeloid leukaemia. The patient was successfully treated with liposomal amphotericin B. The diagnosis of Mucor is very difficult, especially in severely immunocompromised patients. This report seems to be the first case about documented lymph node involvement by mucormycosis in humans.

Topics: Adult; Amphotericin B; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Lymphadenitis; Male; Mucormycosis; Neck

A 36-year-old male with acute myeloid leukaemia was treated with liposomal amphotericin B for a breakthrough fungal infection with Absidia corymbifera during voriconazole and caspofungin therapy for invasive pulmonary aspergillosis. Four episodes of hyperkalaemia developed with a highly probable relation to infusion of liposomal amphotericin B, of which the last episode was characterised by severe, refractory hyperkalaemia and fatal cardiac arrest. The available literature on severe hyperkalaemia and cardiac arrest during administration of both conventional and liposomal amphotericin B is reviewed here and revealed only four similar cases. The most likely mechanism of toxicity is the release of potassium from a variety of mammal cells including erythrocytes and endothelial cells. Whether prevention of toxicity can be established by decreasing the infusion rate is unclear but conceivable.

Topics: Absidia; Adult; Amphotericin B; Antifungal Agents; Fatal Outcome; Heart Arrest; Humans; Hyperkalemia; Leukemia, Myeloid, Acute; Male; Mucormycosis

Gastrointestinal mucormycosis is an uncommon opportunistic fungal infection often presents in immunocompromised patients. Direct invasion of the intestinal walls by spores from ingested food is the main pathogenetic mechanism of this disease, which usually takes place in stomach and colon. Early diagnosis is critical, especially in vascular invasive types, due to its high mortality rate close to 100%. In the past when appropriate diagnostic tools were not available, mucormycosis were frequently found with autopsy. The advance in current endoscopic technology has increased diagnostic rate and made successful management available with appropriate treatments such as debridement of contaminated tissues. In this case report, we discussed a case of ileal mucormycosis diagnosed by colonoscopy and treated with anti-fungal agent successfully.

Topics: Amphotericin B; Antifungal Agents; Colonoscopy; Humans; Ileal Diseases; Ileum; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Mucormycosis; Tomography, X-Ray Computed; Young Adult

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Child; Child, Preschool; Echinocandins; Fatal Outcome; Female; Humans; Kidney; Kidney Diseases; Leukemia, Myeloid, Acute; Lipopeptides; Lung; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tomography, X-Ray Computed

A 47-year-old man with newly diagnosed acute myeloblastic leukemia and non-insulin-dependent diabetes mellitus developed Trichosporon asahii fungemia while receiving caspofungin as empirical antifungal therapy. The diagnosis was based on repeated isolation of T. asahii in culture of blood for three times. Despite treatment with amphotericin B and voriconazole, the patient died. The in vitro antifungal susceptibilities of the T. asahii isolates were only available after the patient died. In vitro antifungal susceptibility tests showed high caspofungin and amphotericin B minimal inhibitory concentrations (MICs) value for this Trichosporon strain (MICs, 16 microg/ml, and>32 microg/ml, respectively). Fluconazole, itraconazole, and voriconazole exhibited low MICs in vitro (MICs, 4 microg/ml, 0.5 microg/ml, and

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Diabetes Mellitus, Type 2; Drug Resistance, Multiple, Fungal; Echinocandins; Fatal Outcome; Fungemia; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Trichosporon

With its broad spectrum of activity and better tolerability profile than conventional amphotericin B, liposomal amphotericin B (L-AmB) may be the drug of choice for antifungal prophylaxis in haematological patients. An open-label, multicentre, prospective, pilot study was conducted in adult patients receiving chemotherapy for acute leukaemia (AL) or myeloablative allogeneic stem cell transplantation (SCT). Patients received weekly 10mg/kg infusions of L-AmB for 4 weeks for AL and 8 weeks for SCT. The primary objective was safety, with particular attention to infusion-related reactions and nephrotoxicity. Twenty-nine adult patients were included: 21 AL (median age 52 years) and 8 SCT (median age 37 years). The most frequent adverse events (AEs) related to study drug were infusion-related reactions, 12 of which (from a total of 76 infusions) led to increased infusion duration for better tolerance. No AE related to the study drug led to discontinuation of prophylactic treatment in AL patients. In SCT patients, eight AEs (in six patients) reported to be related to study treatment led to treatment discontinuation. Enrolment was discontinued in the SCT group as recommended by the independent data review committee in accordance with the 10% limit of AEs (CTC grade 3-4) fixed by the protocol. The appropriate timing of high-dose prophylactic L-AmB remains to be determined in the SCT setting to optimise the safety profile of this regimen. For AL, a 10mg/kg weekly dose appears to be well tolerated during chemotherapy and may represent an important tool towards improving AL patient outcome.

Topics: Adult; Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Pilot Projects; Prospective Studies; Safety

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

We report 2 pediatric cases of cerebral fungal infection. A patient with severe aplastic anemia developed an Aspergillus species brain abscess and pulmonary aspergillosis after peripheral blood stem cell transplantation. Despite administration of micafungin, amphotericin B, and flucytosine, the patient died 2 months after the transplantation because of underlying pulmonary aspergillosis. Another patient with acute myelogenous leukemia developed a huge brain abscess with histopathologic findings suspicious of mucormycosis. This patient was cured with combination therapy of antifungal agents and intensive surgery, without sequelae. It is important to perform aggressive multimodality treatment, when indicated, including surgical intervention, even if in myelosuppression.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Central Nervous System Fungal Infections; Child; Drug Combinations; Echinocandins; Fatal Outcome; Female; Flucytosine; Follow-Up Studies; Graft Rejection; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Magnetic Resonance Imaging; Male; Micafungin; Mucormycosis; Peripheral Blood Stem Cell Transplantation; Remission Induction; Treatment Outcome

A 59-year-old man was admitted to our hospital with a diagnosis of acute myeloid leukemia in September 2004. He developed invasive pulmonary aspergillosis (IPA) and candidiasis, which were improved by administration of micafungin and amphotericin B (AMPH-B). He received reduced-intensity unrelated cord-blood transplantation without induction chemotherapy. He developed grade IV graft-versus-host disease (GVHD) and the administration of steroids against GVHD was prolonged. Voriconazole (VRCZ) was used for a long period to prevent recurrence of the IPA. Afterwards, infiltrates in the bilateral upper lung fields were detected on a chest CT scan, and a diagnosis of pulmonary mucormycosis was made following detection of Mucor circinelloides from the patient's sputum culture. He then began receiving AMPH-B but died of massive hemoptysis. Mucormycosis usually occurs in immunocompromised hosts such as neutropenic patients with hematologic diseases and is a fatal fungal infection characterized by a rapid and progressive clinical course. Some overseas investigators have recently reported that VRCZ prophylaxis may result in breakthrough mucormycosis in hematopoietic stem cell transplant recipients. These findings suggest that it is very important to pay attention to mucormycosis in hematopoietic stem cell transplant recipients in this country.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Cord Blood Stem Cell Transplantation; Echinocandins; Fatal Outcome; Graft vs Host Disease; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Middle Aged; Mucormycosis; Peptides, Cyclic; Pyrimidines; Transplantation Conditioning; Triazoles; Voriconazole

A neutropenic patient with acute myeloid leukaemia experienced a breakthrough infection of Trichosporon asahii during posaconazole treatment. After treatment was changed to a combination therapy with voriconazole and liposomal amphotericin B, the infection resolved. Posaconazole works effectively as an antifungal prophylaxis and salvage therapy in rare invasive fungal infections. This case however illustrates that breakthrough infections with T. asahii may occur during posaconazole treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Cross Infection; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Male; Mycoses; Pyrimidines; Triazoles; Trichosporon; Voriconazole

Topics: Abscess; Amphotericin B; Antifungal Agents; Candidiasis; Dermatomycoses; Extremities; Face; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Diabetic Nephropathies; Humans; Leukemia, Myeloid, Acute; Male; Renal Dialysis

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

Topics: Amphotericin B; Antifungal Agents; Chin; Diabetes Complications; Ecthyma; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Necrosis; Neutropenia; Zygomycosis

Topics: Amphotericin B; Antifungal Agents; Catheterization; Dermatomycoses; Equipment Contamination; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Necrosis; Zygomycosis

Invasive fungal infections are fatal complications for patients on chemotherapy, and antifungal prophylactic treatment has been commonly recommended. Because its clinical and economic impact is not well known, we evaluated cost-effectiveness of anti-fungal treatment for patients who were neutropoenic as a result of chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$), and incremental cost-effectiveness ratio (US$/YLS). The following treatment strategies for fungal infections were compared: (1) prophylactic fluconazole strategy: oral fluconazole administration concurrently with chemotherapy; (2) empirical amphotericin B strategy: empirical intravenous amphotericin B administration at the point where fever is detected; and (3) no prophylaxis strategy: intravenous micafangin administration at the point where fungal infections is diagnosed. Baseline analyses showed that prophylactic fluconazole strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS). The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was 625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to empirical amphotericin B strategy. Baseline result was found to be robust through sensitivity analyses. Our study showed that concurrent administration of oral fluconazole during induction chemotherapy appears to ensure clinical benefits together with acceptable cost-effectiveness.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Cohort Studies; Cost-Benefit Analysis; Echinocandins; Fluconazole; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Opportunistic Infections; Peptides, Cyclic

Mucormycosis is an uncommon opportunistic fungal infection that may develop in immunocompromised patients with conditions such as diabetes mellitus, leukemia, lymphoma, or human immunodeficiency virus (HIV), or after transplantation with immunosupperessive therapy. We report a case of gastric perforation caused by a mucormycosis infection in a patient with acute myelogenous leukemia (AML). The patient was treated successfully with gastrectomy and the aggressive use of intravenous amphotericin B. He is still alive 1 year after his operation.

Topics: Amphotericin B; Antifungal Agents; Gastrectomy; Humans; Immunocompromised Host; Intestinal Perforation; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Stomach; Treatment Outcome

The combination of resection of infected tissue and antifungal therapy is the treatment of choice in mucormycosis. In disseminated mucormycosis, where surgery is impossible, the mortality is almost 90%. We report the first case of disseminated mucormycosis that was cured with a combination therapy of liposomal amphotericin B and posaconazole without surgical intervention.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Liposomes; Middle Aged; Mucormycosis; Rhizomucor; Treatment Outcome; Triazoles

Blastoschizomyces capitatus (formerly known as Geotrichum capitatum and Trichosporon capitatum) is a rare, yet an emerging, cause of invasive infections in immunosuppressed patients. Profound and prolonged neutropenia is the crucial predisposing factor for this yeast infection. Blastoschizomyces capitatus was isolated from peripheral blood cultures of a profoundly neutropenic patient with acute myeloid leukemia (M2 FAB). Despite administration of antifungal chemotherapy with liposomal amphotericin B at 4.5 mg kg(-1) daily, the patient succumbed 4 days after initiation of treatment. Infections attributed to B. capitatus have generally a poor prognosis, although the yeast shows in vitro susceptibility to antifungal agents. Low flucytosine, caspofungin acetate, voriconazole and amphotericin B minimum inhibitory concentration values were also recorded with our isolate. The clinical relevance of the in vitro susceptibility testing against the isolate and the current antifungal chemotherapy regimens against B. capitatus systemic infections are discussed.

Topics: Aged; Amphotericin B; Antifungal Agents; Blood; Fatal Outcome; Fungemia; Geotrichosis; Geotrichum; Greece; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Sepsis

Topics: Amphotericin B; Combined Modality Therapy; Endoscopy; Ethmoid Sinus; Ethmoid Sinusitis; Female; Humans; Leukemia, Myeloid, Acute; Maxillary Sinusitis; Middle Aged; Nasal Mucosa; Opportunistic Infections; Orbital Diseases; Rhinitis; Tomography, X-Ray Computed

Topics: Amphotericin B; Antifungal Agents; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Rhizopus; Triazoles; Zygomycosis

Genera of the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea) cause an angioinvasive infection called zygomycosis. Mortality rates can approach 100% depending on the patient's underlying disease and form of zygomycosis. We report here on the unusual case of a patient with acute myelogenous leukemia and zygomycosis unresponsive to monotherapy with liposomal amphotericin B, who responded favorably following the addition of the echinocandin caspofungin acetate.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Caspofungin; Combined Modality Therapy; Cytarabine; Debridement; Diplopia; Drug Therapy, Combination; Echinocandins; Humans; Idarubicin; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Middle Aged; Mitoxantrone; Opportunistic Infections; Orbital Diseases; Peptides, Cyclic; Sinusitis; Zygomycosis

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.

Topics: Amphotericin B; Antifungal Agents; Dermatomycoses; Drug Therapy, Combination; Fusarium; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Naphthalenes; Neutropenia; Terbinafine; Treatment Outcome

Topics: Amphotericin B; Antiprotozoal Agents; Humans; Leishmaniasis, Visceral; Leukemia, Myeloid, Acute; Male; Middle Aged; Opportunistic Infections; Stem Cell Transplantation; Treatment Outcome

We report a 44-year-old patient with refractory acute myeloid leukemia who developed a rare form of disseminated cutaneous aspergillosis resulting from colonization in the deep reticular dermis of Aspergillus flavus. Diagnosis was based on cutaneous biopsy. Antifungal therapy was started with liposomal amphotericin B (L AmB). However, the lesions continued to spread and there was a marked decline in the patient's clinical condition. Consequently, L AmB was replaced with voriconazole. Response to voriconazole was excellent with regression of the skin lesions and a rapid improvement of the patient's general clinical condition.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Dermatomycoses; Female; Humans; Leukemia, Myeloid, Acute; Pyrimidines; Triazoles; Voriconazole

Topics: Administration, Intranasal; Adult; Amphotericin B; Aspergillosis; Granulocytes; Humans; Leukemia, Myeloid, Acute; Leukocyte Transfusion; Nose Diseases; Opportunistic Infections

Data on the use of combination of liposomal amphotericin B and caspofungin followed by voriconazole, as maintenance or further rescue treatment, in 10 patients with invasive mycosis are reported.. The diagnoses were acute leukemia (7), myelodysplastic syndrome (1) and Hodgkin's lymphoma (1). All patients developed an invasive mycosis (proven, 3; probable, 6; and possible, 1) refractory to first-line antifungal treatment (liposomal amphotericin B in all patients except one who received fluconazole).. Rescue therapy with a combination of caspofungin and liposomal amphotericin B was well tolerated, hypokalemia, and thrombophlebitis being the most common side-effects. Combination therapy was administered for a median of 17 d, range 6-40. Among the nine patients with proven or probable mycosis, one was not evaluated because of early death caused by massive hemoptysis whilst in the remaining eight patients, the response was classified as complete, stable and failure in four, three, and one patients, respectively. Complete response was also observed in patient with possible mycosis. Eight of nine patients received voriconazole for a median of 75 d, range 42-194. Voriconazole was well tolerated although some drug interactions were observed during treatment with methotrexate and digoxin. After a median follow-up of 125 d, nine of 10 patients are alive. Overall, a favorable response to antifungal treatment (including the case of possible mycosis) was obtained in eight of 10 patients.. These data suggest that medical antifungal treatment may be intensified in severely ill patients without significantly compromising patient safety. The combination of synergistic antifungal drugs as well as their sequential use warrants further investigation by a larger randomized controlled study.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Caspofungin; Child; Drug Synergism; Drug Therapy, Combination; Echinocandins; Female; Geotrichosis; Hodgkin Disease; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Liposomes; Male; Mycoses; Myelodysplastic Syndromes; Peptides; Peptides, Cyclic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Survival Rate; Treatment Outcome; Triazoles; Voriconazole

To report the development of nephrogenic diabetes insipidus (NDI) associated with the use of high-dose liposomal amphotericin B.. A 38-year-old white man with relapsed acute myelogenous leukemia underwent a matched unrelated donor allogeneic bone marrow transplant with adequate engraftment and mild graft-versus-host disease responding to corticosteroids. Approximately 11 months after transplant, the patient was admitted to the hospital with suspected fungal pneumonia and started on liposomal amphotericin B (baseline serum creatinine 1.4-1.5 mg/dL). The dose was increased due to his immunosuppression and poor response, as the fungal etiology was identified as Torulopsis glabrata. The patient required mechanical ventilation due to biopsy-proven bronchiolitis olbiterans organizing pneumonia. Additionally, he developed diffuse alveolar hemorrhage and received intravenous desmopressin, with a reduction in bloody secretions. He also developed hypernatremia (serum sodium 155 mEq/L) on day 3 of the desmopressin and had an inappropriately increased urine output consistent with NDI. The most likely etiology for the NDI was liposomal amphotericin B and its associated hypokalemia.. The observation of worsening hypernatremia (serum sodium increased from 135 to 164 mEq/L) with polyuria was associated with an increasing cumulative dosage of liposomal amphotericin B for fungal pneumonia despite the concurrent use of intravenous desmopressin. Aggressive water replacement was an effective treatment option in this patient. The Naranjo probability scale classified this as a possible adverse reaction because of the temporal sequence of NDI after high-dose liposomal amphotericin B and previously reported cases of NDI associated with amphotericin B desoxycholate.. Amphotericin B desoxycholate has been implicated as an etiology for NDI, and the use of the newer liposomal amphotericin B reportedly avoids this rare complication. We observed the development of NDI despite the use of liposomal amphotericin B in a critically ill patient with bone marrow transplant.

Topics: Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candida glabrata; Diabetes Insipidus, Nephrogenic; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Male; Pneumonia

Although the most common orofacial fungal infection in immunocompromised patients is candidosis, infections caused by virulent molds, such as Aspergillus spp. and Furarium spp. are being recognized with increasing frequency. We report a case of oral Exophiala infection in a 39-year-old woman with acute myeloid leukemia.. Clinical records of the patient were reviewed and the following additional information was collected: histological and microbiological evidence; identification of the causative organism; in vitro antifungal susceptibility.. The patient developed a necrotic ulcer surrounded by a violaceous rim in the gingiva during neutropenia. Exophiala dermatitidis was identified as the causative organism by histopathological examination and culture, and finally confirmed by sequencing of the ribosomal DNA internal transcribed space domain. In vitro, amphotericin B was found to show strong activity against the Exophiala isolate while itraconazole showed less activity. The patient was successfully treated with parenteral amphotericin B and oral itraconazole in combination with surgical removal of the fungi focus.. Local excision with adequate antifungal agents can be used to treat immunocompromised patients with Exophiala stomatitis, based on early diagnosis.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; DNA, Fungal; Exophiala; Female; Humans; Immunocompromised Host; Infusions, Intravenous; Itraconazole; Leukemia, Myeloid, Acute; Mycoses; Neutropenia; Stomatitis

Invasive aspergillosis is a severe, devastating fungal infection that is seen in patients with hematologic malignancies and profound neutropenia. Despite aggressive treatment, the outcome is poor without neutrophil recovery. The authors describe two children with acute myelogenous leukemia (AML) with extensive invasive aspergillosis who were successfully treated both for their infection and the underlying malignancy. These patients were treated aggressively for their infections and simultaneously were able to complete treatment of their AML. Currently both patients are alive without evidence of fungal infection or AML. Patients with hematologic malignancies can survive severe, invasive aspergillosis during prolonged periods of neutropenia with a combination of antifungal and growth factor therapies, donor granulocyte infusions, and surgical debridement.

Topics: Adolescent; Amphotericin B; Aspergillosis; Granulocyte Colony-Stimulating Factor; Humans; Infant; Leukemia, Myeloid, Acute; Male

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Discitis; Drug Therapy, Combination; Humans; Itraconazole; Leukemia, Myeloid, Acute; Male; Middle Aged; Opportunistic Infections; Osteomyelitis; Scedosporium; Sepsis

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bronchi; Female; Glycoproteins; Humans; Injections; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Opportunistic Infections; Tomography, X-Ray Computed; Trypsin Inhibitors

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Child; Drug Combinations; Drug Therapy, Combination; Echinocandins; Female; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Neutropenia; Peptides; Peptides, Cyclic; Phosphatidylcholines; Phosphatidylglycerols; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Child; Dermatomycoses; Humans; Leukemia, Myeloid, Acute; Male; Severity of Illness Index; Therapeutic Irrigation

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Chronic Disease; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Risk Factors; Spleen; Splenectomy; Treatment Failure

We describe a 12-year-old boy with acute myeloid leukemia who developed pleuropericarditis while he was neutropenic and was receiving intravenously administered antibiotic and antifungal therapy for pneumonia. A KOH preparation of the purulent material from an extensive diagnostic and therapeutic pleuropericardial drainage procedure revealed multiple irregularly septate hyphae, and cultures yielded the organism Pythium insidiosum. After completing a 12-month course of intravenously administered liposomal amphotericin B (AmBisome; Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical remission, and symptom free.

Topics: Amphotericin B; Antifungal Agents; Child; Humans; Leukemia, Myeloid, Acute; Male; Pericarditis; Pneumonia; Pythium

A series of cases are presented to illustrate the complexity of the care of immunocompromised patients with established invasive fungal infections. These discussions by an expert panel serve to identify areas of controversy and for future research in the care of transplant recipients.

Topics: Adult; Aged; Amphotericin B; Aspergillus fumigatus; Candida; Candida glabrata; Female; Fluconazole; Humans; Kidney; Leukemia, Myeloid, Acute; Lung Transplantation; Male; Middle Aged; Mycoses; Sinusitis; Transplantation

Due to an increasing number of leukemic patients with invasive gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10 days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing this invasive infection at our hospital.. This was a retrospective, non-randomized study to analyze the onset of identified invasive gingival aspergillosis among 536 patients with acute leukemia at risk due to the presence of neutropenia from 1991 to 1998. Patients received itraconazole capsules 100 mg/day prophylactically between April 1994 and December 1996, and 200 mg/day between January 1997 and December 1998. Itraconazole serum levels at day 10 were measured in some patients.. In the 39 months prior to April 1994 without itraconazole prophylaxis, 15 cases of invasive gingival aspergillosis were detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the high risk patients). Between April 1994 and December 1996, using itraconazole prophylaxis at 100 mg/day, there was a dramatic decrease in the infections resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5% of the high risk patients). Furthermore, between January 1997 and December 1998, using itraconazole prophylaxis at 200 mg/day, no cases of the infection were observed in the 146 high risk patients with 380 episodes of neutropenia. The incidence of invasive gingival aspergillosis was significantly lower among patients administered itraconazole than among those without itraconazole (100 mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving 200 mg/day was 202.67 ng/ml.. These findings suggest that oral itraconazole could be effective for preventing invasive gingival aspergillosis in neutropenic patients with acute leukemia and warrants further randomized investigation.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis, Oral; Capsules; Chi-Square Distribution; Chromatography, High Pressure Liquid; Cohort Studies; Fluconazole; Flucytosine; Gingival Diseases; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid, Acute; Leukocyte Count; Neutropenia; Neutrophils; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Treatment Outcome

Invasive fungal infections are associated with high morbidity and mortality in immunocompromised patients. We describe an unusual case of concomitant invasive candidiasis and zygomycosis of the tongue and epiglottis that occurred in a young patient with neutropenia during chemotherapy for acute myelogenous leukemia and was successfully treated medically.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida; Candidiasis; Cytarabine; Epiglottis; Fungi; Humans; Idarubicin; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Neutropenia; Tongue; Tongue Diseases; Zygomycosis

Invasive pulmonary aspergillosis is a serious problem in the treatment of patients with acute leukemia. A 52-year-old woman with acute myeloid leukemia developed invasive pulmonary aspergillosis during remission induction chemotherapy. Initially, we treated her with a continuous intravenous drip infusion of amphotericin B, together with itraconazole, given orally. A peripheral crescentic cavity formed in the fungal lesion after the number of neutrophils recovered, and we therefore performed a direct infusion of miconazole into the cavity transbronchially. The lung lesion resolved dramatically shortly after this treatment. In this patient, the transbronchial infusion of an antifungal agent seemed to have been very useful for bringing about prompt resolution of the fungal lesion.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Female; Humans; Itraconazole; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Middle Aged

Invasive aspergillosis is uncommon in immunocompetent hosts but is the second most common opportunistic fungal infection in immunocompromised patients. There has been a dramatic increase in the incidence of life-threatening aspergillosis during the past 2 decades, and the morbidity and mortality of these infections despite antifungal therapy remain unacceptably high. We describe a patient with amphotericin B-resistant Aspergillus flavus successfully treated with caspofungin, an agent belonging to a new class of antifungal drugs. Caspofungin shows great promise in the treatment of invasive aspergillosis.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Arm; Aspergillosis; Aspergillus flavus; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Peptides; Peptides, Cyclic

To describe a patient who developed adverse reactions to two different lipid formulations of amphotericin B: liposomal amphotericin B (AmBisome) and amphotericin B colloidal dispersion (ABCD, Amphocil), yet tolerated amphotericin B deoxycholate (Fungizone) despite renal toxicity.. A 72-year-old woman with acute myelomonocytic leukemia was treated with amphotericin B deoxycholate for suspected pulmonary aspergillosis; the drug was well tolerated but resulted in renal failure. Antifungal therapy was then changed to liposomal amphotericin B. Within 10 minutes of liposomal amphotericin B infusion, the patient developed severe dyspnea, chest pain, and a feeling of imminent death. On the following day, liposomal amphotericin B was switched to amphotericin B colloidal dispersion. Again, within 10 minutes of this infusion, the patient developed fever, chills, hypotension, severe chest pain, dsypnea, and a feeling of imminent death. The patient refused any further treatment with these drugs and insisted on switching back to amphotericin B deoxycholate, which was then administered for 10 days and was well tolerated.. Severe adverse reactions, such as anaphylaxis, cardiac toxicity, and respiratory failure, following administration of all three lipid formulations of amphotericin B have been reported. In most reported cases, switching to a different lipid formulation of amphotericin B was well tolerated. This is in contrast to our case, where a severe reaction was repeated when another lipid preparation was given, necessitating switching back to amphotericin B deoxycholate despite its nephrotoxicity.. In some patients, paradoxically, lipid formulations of amphotericin B may be less tolerable than conventional amphotericin B.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Colloids; Female; Humans; Leukemia, Myeloid, Acute; Liposomes

We report our recent experience with two cases of invasive pulmonary aspergillosis in patients who were both undergoing chemotherapy, one for acute myeloid leukaemia and the other for primary amyloidosis. Both patients had bad prognostic factors and were in very poor clinical condition, but both recovered from infection after a prolonged therapy with liposomal amphotericin B (AmBisome) without signs of toxicity.

Topics: Aged; Amphotericin B; Amyloidosis; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Brain Diseases; Fatal Outcome; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged

Trichophyton rubrum is the most widely encountered dermatophyte infection, and is usually regarded as exclusively keratinophilic often leading to chronic cutaneous and nail infections, even in healthy individuals. We present three patients with acute leukaemias, with ill-defined pre-existent cutaneous eruptions that were treated with a potent topical corticosteroid. All three patients received aggressive marrow toxic chemotherapy. These patients had progression of their cutaneous disease, which showed deep dermal invasion of T. rubrum, invading directly from the epidermis with no evidence of systemic spread. We conclude that systemic pancytopenia, in association with prolonged local immunosuppression, may increase the risk of direct dermal invasion of dermatophyte infections. However, even in these patients, the risk of systemic spread still appears very low. Amphotericin B did not appear effective in treating these dermatophyte infections.

Topics: Adolescent; Adult; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Fluconazole; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Naphthalenes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Steroids; Terbinafine; Tinea; Treatment Outcome; Trichophyton

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Tomography, X-Ray Computed

We report the first case of invasive pulmonary infection caused by the thermotolerant ascomycetous fungus Gymnascella hyalinospora in a 43-year-old female from the rural midwestern United States. The patient was diagnosed with acute myelogenous leukemia and treated with induction chemotherapy. She was discharged in stable condition with an absolute neutrophil count of 100 cells per microliter. Four days after discharge, she presented to the Cancer Clinic with fever and pancytopenia. A solitary pulmonary nodule was found in the right middle lobe which was resected by video-assisted thoracoscopy (VATHS). Histopathological examination revealed septate branching hyphae, suggesting a diagnosis of invasive aspergillosis; however, occasional yeast-like cells were also present. The culture grew a mold that appeared dull white with a slight brownish tint that failed to sporulate on standard media. The mold was found to be positive by the AccuProbe Blastomyces dermatitidis Culture ID Test (Gen-Probe Inc., San Diego, Calif.), but this result appeared to be incompatible with the morphology of the structures in tissue. The patient was removed from consideration for stem cell transplant and was treated for 6 weeks with amphotericin B (AmB), followed by itraconazole (Itr). A VATHS with biopsy performed 6 months later showed no evidence of mold infection. In vitro, the isolate appeared to be susceptible to AmB and resistant to fluconazole and 5-fluorocytosine. Results for Itr could not be obtained for the case isolate due to its failure to grow in polyethylene glycol used to solubilize the drug; however, MICs for a second isolate appeared to be elevated. The case isolate was subsequently identified as G. hyalinospora based on its formation of oblate, smooth-walled ascospores within yellow or yellow-green tufts of aerial hyphae on sporulation media. Repeat testing with the Blastomyces probe demonstrated false-positive results with the case isolate and a reference isolate of G. hyalinospora. This case demonstrates that both histopathologic and cultural features should be considered for the proper interpretation of this molecular test and extends the list of fungi recognized as a cause of human mycosis in immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Ascomycota; Cytarabine; Drug Resistance, Microbial; Female; Humans; Idarubicin; Itraconazole; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Midwestern United States; Mycological Typing Techniques

A 73-y-old female with a history of adenocarcinoma of colon and refractory anemia developed febrile neutropenia following chemotherapy. Therapy with iv infusion of amphotericin B deoxycholate (AmBd) was initiated on day 8 of hospital admission. Premedications included acetaminophen, diphenhydramine and meperidine. Patient developed rigor, chill and elevated temperature approximately 100 min into the infusion. The infusion was temporarily discontinued and rigors subsided following administration of 25 mg meperidine im. Infusion was continued after cessation of the rigors with no further sequelae. During each infusion of AmBd over the next 3 d, the patient developed rigor, chill and elevated temperature which was managed with meperidine. However, on day 4 she developed respiratory distress, bronchospasm and visible cyanosis with oxygen saturation of 88% while on 2 L oxygen. The infusion was stopped and the symptoms subsided with administration of albuterol via nebulizer. Amphotericin lipid formulation infusion was reinstituted after 3 d because of the patient's worsening clinical status. However, the patient developed severe respiratory distress approximately 130 min into the infusion. The infusion was discontinued and she was treated with albuterol via nebulizer. Itraconazole therapy was instituted without any adverse sequelae. Clinicians should be aware of this potential adverse event since it can occur with all formulation of amphotericin.

Topics: Adenocarcinoma; Aged; Amphotericin B; Anemia; Antifungal Agents; Colonic Neoplasms; Drug Combinations; Female; Fever; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Respiratory Distress Syndrome

Topics: Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Aspergillus; Humans; Leukemia, Myeloid, Acute; Male; Opportunistic Infections; Rhinitis; Sinusitis; Tomography, X-Ray Computed

We would like to report the use of liposomal amphotericin in eradicating mucormycosis in two patients who had relapsed acute leukaemia. The first patient with relapsed acute myeloid leukaemia developed a rapidly expanding solitary necrotic neck lesion associated with opacity of maxilliary sinus at a time when he was profoundly pancytopenic following high dose chemotherapy. The second patient was a 3-year-old boy with pre-B acute lymphoblastic leukaemia who developed a central nervous system relapse whilst on his first line treatment and was treated with more aggressive chemotherapy on the Medical Research Council Relapse Protocol. During a period of profound pancytopenia following re-induction therapy, including high dose steroids and prolonged course of antibiotics for proven septicaemia, he developed periorbital swelling and proptosis and a clinical diagnosis of rhinocerebral mucormycosis was made. Both patients were treated with high doses of liposomal amphotericin (Ambisome Nexstar). The doses were escalated to 10 and 15 mg/kg/day, resulting in successful eradication of the mucormycosis.

Topics: Absidia; Adolescent; Amphotericin B; Antifungal Agents; Child, Preschool; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Mucormycosis; Opportunistic Infections; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Zygomycosis

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

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

Patients with hematology disease in post-chemotherapy medullary aplasia are susceptible to life-threatening bronchopulmonary mycoses, especially aspergillosis. Other less common pulmonary mycoses are also observed. We report 4 cases due to Penicillium purpurogenum, Acromonium strictum and Scedosporium apiospermum (n = 2) infections. These unusual fungi appear to be emerging as pathogens in this population. They have common ubiquitous, opportunistic and low pathogenicity characteristics in immunocompetent subjects. The major risk factor is neutropenia. Isolating one of these fungi in an immunodepressed patient modifies management protocols since certain unusual fungi such as Scedosporium are resistant to amphotericin B.

Topics: Acremonium; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Bone Marrow Transplantation; Female; Hematologic Neoplasms; Humans; Imidazoles; Leukemia, Myeloid, Acute; Lung; Lung Diseases, Fungal; Male; Middle Aged; Multiple Myeloma; Neutropenia; Penicillium; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudallescheria; Pyrimidines; Risk Factors; Triazoles; Voriconazole

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liver Abscess; Male; Opportunistic Infections; Treatment Outcome

Infections with fluconazole-resistant Candida albicans isolate have rarely been described in clinical settings other than oropharyngeal candidiasis in patients with late-stage AIDS. We report on two patients with leukemia who developed fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body weight per day). The fluconazole MICs for the isolates were > or = 64 micrograms/ml, and the isolates were resistant to other azoles and had membrane sterol changes consistent with a mutation in the delta 5,6-sterol desaturase gene. The lack of ergosterol in the cytoplasmic membrane of the fluconazole-resistant strains also imparted resistance to amphotericin B. Both patients were successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and flucytosine (150 mg/kg/day).

Topics: Adolescent; Adult; Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Resistance, Multiple; Female; Fluconazole; Flucytosine; Fungemia; Humans; Leukemia, Myeloid, Acute; Male; Mice; Microbial Sensitivity Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Virulence

Primary invasive aspergillosis of the oral cavity is a rare but serious complication in immunocompromised patients. We report a case of gingival Aspergillus infection in a neutropenic patient with acute myelogenous leukemia, who was successfully treated by an early surgical approach in combination with antifungal medication and granulocyte colon stimulating factors.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Fluconazole; Flucytosine; Gingival Diseases; Granulocyte Colony-Stimulating Factor; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid, Acute; Neutropenia

A 58-year-old woman with acute myelogenous leukemia in complete remission underwent successful pulmonary resection for massive hemoptysis occurring after resolution of pulmonary aspergillosis. Despite the fact that the role of surgery in the treatment of pulmonary mycosis in immunocompromised hosts is still to be clearly defined, emergency lung resections can be successfully performed in this group of patients with almost immediate recovery of stable clinical parameters. Brisk recovery can reduce overall morbidity and mortality and allow for early resumption of any necessary treatment for underlying disease.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Fatal Outcome; Female; Hemoptysis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung; Lung Diseases; Middle Aged; Radiography, Thoracic; Salvage Therapy

Aspergillus sinusitis is usually a lethal condition in bone marrow transplanted patients. We report the case of a patient known to have a sinus infection with Aspergillus flavus before treatment with allogenic bone marrow transplantation for a refractory acute myelogenous leukemia. Exacerbation of the sinusitis during the neutropenic period required a multidisciplinary approach. Cure was achieved after treatment with a combination of surgery (Caldwell-Luc procedure), long term ABCD (amphotericin B colloidal dispersion) therapy (7 months) and granulocyte transfusions during the period preceding engraftment. The use of granulocyte transfusion in this salvage setting is discussed. Aggressive multimodality management of aspergillus sinusitis in immunosuppressed patients may lead to a cure and might not preclude allogenic transplantation.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Female; Granulocytes; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Leukocyte Transfusion; Neutropenia; Sinusitis

Invasive opportunistic mycoses are common complications in patients suffering from hematological disorders. Brain abscesses in the immunocompromised host are known to be most frequently caused by fungi of the Aspergillus species and are often associated with concomitant pulmonary disease. As the penetration of the currently available antifungal agents into the brain tissue is limited, only very few patients have been described to survive this life-threatening condition. We report the case of a 62 year old female patient who presented with multiple aspergillus brain abscesses during prolonged neutropenia following induction chemotherapy for acute myeloblastic leukemia and was successfully treated with high dose (8 mg/kg/day) liposomal amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Brain Abscess; Female; Humans; Leukemia, Myeloid, Acute; Liposomes; Middle Aged

Phialophora is a dematiaceous fungus isolated from soil and wood. Human infections including chromoblastomycosis, mycotic keratitis, cutaneous infections, and prosthetic valve endocarditis have been reported. We report a case of fatal hemorrhage due to Phialophora verrucosa in a patient with prolonged neutropenia undergoing autologous bone marrow transplant (BMT) for acute myelogenous leukemia (AML). Bacterial infections complicated induction and consolidation chemotherapies. Liposomal amphotericin B (LAMB) was given from day +33 to day +72 for febrile neutropenia. Death occurred on day +74 due to tracheal hemorrhage. Autopsy revealed granulation tissue on the posterior wall of the trachea with fungal hyphae on histopathology; the tissue grew Phialophora verrucosa. In vitro susceptibility studies revealed a minimum inhibitory concentration to AmB of 0.1 microg/ml. This represents the first reported case of invasive P. verrucosa in a BMT patient leading to fatal hemorrhage, despite large cumulative doses of LAMB to which the organism remained susceptible.

Topics: Adult; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Bone Marrow Transplantation; Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Liposomes; Mycoses; Neutropenia; Phialophora; Trachea

Multiple necrotizing skin lesions due to Fusarium solani in an elderly man with acute myelogenous leukemia is described.

Topics: Amphotericin B; Antifungal Agents; Dermatomycoses; Female; Fluconazole; Fusarium; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Necrosis; Skin

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Infections; Leukemia, Myeloid, Acute; Prototheca

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous mucor infection developed in two children who had undergone bone marrow transplantation for treatment of leukemia. One infection occurred before transplantation, and the other occurred during the period of profound neutropenia after transplantation. Both children were treated with an extensive wide excision of the infected area, and there was no evidence of mucor along the resected edges of tissue. Both patients received extensive treatment with either amphotericin (case 1) or amphotericin and itraconazole (case 2). These two cases represent aggressive management of cutaneous mucor infections, which is believed to be required for the successful completion of a marrow transplantation procedure.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Dermatomycoses; Female; Humans; Itraconazole; Leukemia, Myeloid, Acute; Male; Mucormycosis; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhizopus

Topics: Amphotericin B; Antifungal Agents; Female; Fungemia; Humans; Leukemia, Myeloid, Acute; Middle Aged; Pichia

We describe five patients with acute leukemia who during the period of chemotherapy-induced neutropenia developed invasive pulmonary aspergillosis. Amphotericin B was initiated early in the febrile neutropenic episode at a dose of 1-1.5 mg/kg per day. Four of the five patients had normal chest films at the time amphotericin B was started and only later developed infiltrates, which subsequently progressed to cavitation formation with resolution of the infiltrates around the cavitations. This is compatible with primary aspergilloma or invasive pulmonary aspergillosis. The patients experienced partial (2 patients) or complete resolution (3 patients) of the process, and none died of the fungal infection. In the past, infection with invasive aspergillosis carried a high mortality. We believe that this positive outcome constitutes a change in the natural history of invasive pulmonary aspergillosis in neutropenic patients as a result of the early initiation of high dose amphotericin B. We recommend the early empiric use of amphotericin B therapy in febrile neutropenic patients not responding to broad-spectrum antibiotics, and that the minimal initial dose be 1 mg/kg per day especially in institutions carrying a high incidence of aspergillosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

The aim of this study was to review the eight histopathologically proven cases of invasive fungal sinusitis that occurred at the Toronto Hospital for Sick Children between 1985 and 1995, seven of which that clustered between March 1990 and February 1992.. A retrospective review of the relevant cases and a review of the literature are presented.. A clinical review of this rare, life-threatening entity, occurring almost exclusively in severely neutropenic patients is presented and compared to the relevant clinical findings from an analysis of this series, the largest reported to date and first to document a significant clustering (p < .01).. We conclude, based on epidemiologic evidence, that this clustering was directly related to the release of airborne fungal spores from dormant soil reservoirs disturbed during hospital construction. Therefore, we strongly advocate increased vigilance with respect to precautions against airborne pathogens wherever severely neutropenic hosts are treated.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillus; Child; Female; Humans; Leukemia, Myeloid, Acute; Male; Mucor; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sinusitis; Wilms Tumor

Topics: Amphotericin B; Dermatomycoses; Female; Fusarium; Humans; Leukemia, Myeloid, Acute; Liposomes; Middle Aged; Neutropenia

Topics: Aged; Amphotericin B; Anaphylaxis; Asthma; Candidiasis; Desensitization, Immunologic; Drug Resistance, Microbial; Emergency Medical Services; Female; Humans; Leukemia, Myeloid, Acute; Neutropenia

Opportunistic mycotic infections, such as aspergillosis, can produce morbid consequences with or without aggressive therapy in an immunocompromised patient. Treatment including amphotericin B and resection of the infected tissue must be considered early in the overall management of the patient. We describe two patients with acute myelogenous leukemia who underwent intense cytoreductive therapy with bone marrow transplantation and an associated fungal infection treated with an investigational form of amphotericin B.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Oroantral Fistula; Sinusitis; Stomatitis; Tomography, X-Ray Computed

Herein we report the successful treatment of invasive aspergillosis with the liposomal amphotericin B (AMB) formulation, Amphotericin B Lipid Complex (ABLC). This investigational compound was employed in a 50-year-old patient with acute myelomonocytic leukemia complicated by prolonged, treatment-induced granulocytopenia and documented Aspergillus flavus sinusitis with signs of disseminated aspergillosis. The patient demonstrated radiographic signs of pulmonary aspergillosis and biochemical signs of hepatic involvement that were resistant to a 23 day course of conventional AMB (Fungizone) therapy. Following therapy with ABLC her fever abated, her chest X-ray findings improved, and her hepatic function tests improved with eventual resolution.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Female; Humans; Leukemia, Myeloid, Acute; Liposomes; Lung Diseases, Fungal; Neutropenia; Time Factors

The fungus Fusarium moniliforme causes fusariosis, which can be invasive and fatal in immunocompromised patients. We report a case of oral Fusarium infection in a granulocytopenic patient with acute myelogenous leukemia who developed necrotic ulceration of the gingiva, extending to the alveolar bone, but was otherwise free of any active systemic lesions. Fusarium moniliforme was identified, by histopathology and culture, to be present in the lesion and was deduced to be the causative organism for this invasive oral infection.

Topics: Acute Kidney Injury; Aged; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Epirubicin; Etoposide; Fatal Outcome; Fusarium; Gingival Diseases; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Maxillary Diseases; Mercaptopurine; Mycoses; Necrosis; Prednisolone; Ulcer; Vindesine

Pulmonary toxicity with acute dyspnea occurred during infusion of a liposomal amphotericin B preparation (AmBisome) in two adult leukemic patients. The preparation was administered as a one hour infusion at a dose of 3 mg/kg body weight. Within 15 min after starting the infusion, both patients experienced sudden onset of dyspnea and chest tightness. Physical examination showed the patients to be anxious and restless with tachycardia and orthopnea but without other cardiopulmonary findings. No elevation of body temperature, rigors or chills were recorded. Symptoms disappeared within minutes after discontinuing the infusion. At present, the pathophysiologic mechanisms underlying these side effects are unknown.

Topics: Acute Disease; Amphotericin B; Drug Carriers; Dyspnea; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Respiratory System

Encephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high-dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high-dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non-central nervous system Epstein-Barr virus-lymphoproliferative disease and had autopsy-confirmed leukoenephalopathy.

Topics: Adolescent; Amphotericin B; Antineoplastic Agents; Aspergillosis; Bone Marrow Transplantation; Brain Diseases; Child; Cyclophosphamide; Cytarabine; Humans; Leukemia, Myeloid, Acute; Lung Diseases; Male; Methotrexate; Parkinson Disease; Radiation Injuries

A 49-year-old male was admitted with a diagnosis of AML (M2). One course of BHAC-DM regimen induced complete remission. During the consolidation therapy, he developed marked pyrexia resistent to antibiotics. Ultrasonography and CT scan revealed multiple small liver abscesses, which suggested mycotic etiology. After unsuccessful treatment with intravenous administration of fluconazole, a percutaneous transhepatic intraportal administration of Amphotericin B (AMPH-B) (20 mg/day) was started, followed by the consolidation chemotherapy. When the first positive blood culture was obtained for Candida, a reservoir was embedded in the subcutaneous layer of the right iliac region and the intrahepatic arterial administration of AMPH-B (5 to 20 mg/day) by the Infusor (Baxter Healthcare Corporation), a portable, disposable drug delivery system that provides a constant drug flow, was started. The liver abscesses has almost disappeared when the maintenance chemotherapy was completed. The side effects of AMPH-B were negligible. This case suggests the usefulness of the intrahepatic arterial infusion of AMPH-B using an inplantable drug delivery system in patients with hematological malignancies developing intractable multiple fungal liver abscesses.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Disposable Equipment; Hepatic Artery; Humans; Immunocompromised Host; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leukemia, Myeloid, Acute; Liver Abscess; Male; Middle Aged

Mucor circinelloides form circinelloides has rarely been associated with human disease, even in immunocompromised patients. We report a case of cutaneous zygomycosis caused by M. circinelloides in a 23-year-old neutropenic woman receiving consolidation chemotherapy for acute myelogenous leukemia. The organism was exquisitely susceptible to amphotericin B. Despite the fact that the patient was profoundly neutropenic for an additional 3 weeks, the lesions began to resolve during therapy, and no surgical debridement was required.

Topics: Adult; Amphotericin B; Antineoplastic Agents; Dermatomycoses; Drug Resistance, Microbial; Female; Humans; Leukemia, Myeloid, Acute; Mucor; Mucormycosis; Neutropenia; Opportunistic Infections

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: Adult; Amphotericin B; Bone Marrow Transplantation; Diabetes Insipidus; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Liposomes; Male

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

Patients with previous invasive fungal infections (IFI) are at high risk of reactivation of the infection during BMT, even after an apparently curative antifungal treatment. We report four patients who suffered an IFI after intensive chemotherapy for acute leukemia and were later submitted for BMT. One patient had developed a chronic systemic candidiasis during consolidation chemotherapy and received prophylactic oral or iv fluconazole (200 mg daily) throughout BMT. Two patients developed an invasive pulmonary aspergillosis after intensive chemotherapy, one of them after salvage therapy for post-allogeneic BMT relapse and the other after consolidation therapy. The former patient underwent partial lobectomy after treatment with amphotericin B before a second allogeneic BMT was performed. Both patients received prophylactic itraconazole (400 mg daily by mouth) throughout the BMT procedure. The fourth patient had pneumonia caused by Scedosporium apiospermum (the anamorph form of the fungus Pseudallescheria boydii) during consolidation chemotherapy which was successfully treated with itraconazole. During BMT he also received oral itraconazole (400 mg daily) as prophylaxis against reactivation of the infection. All four patients had successful BMT and none had clinical, radiological or microbiological evidence of reactivation of IFI during BMT.

Topics: Administration, Oral; Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus; Bone Marrow Transplantation; Candida; Candidiasis; Female; Fluconazole; Humans; Incidence; Itraconazole; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Mycetoma; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudallescheria; Recurrence; Risk Factors

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

One case has been reported of a patient undergoing allogeneic transplantation with peripheral blood progenitor cells (PBPCs) rather than bone marrow. We now report the first case of a patient who underwent an allogeneic transplant with bone marrow combined with PBPCs.

Topics: Amphotericin B; Aspergillosis; Blood Component Transfusion; Bone Marrow Purging; Bone Marrow Transplantation; Child; Colony-Stimulating Factors; Combined Modality Therapy; Fatal Outcome; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunologic Factors; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Recombinant Proteins; Salvage Therapy; Transplantation, Homologous

Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.

Topics: Adolescent; Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Female; Graft Survival; Humans; Immunocompromised Host; Incidence; Itraconazole; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Survival Analysis; Treatment Outcome

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with neutropenia. Two severe complications with poor outcome can be observed after apparently successful IPA medical treatment: severe hemoptysis and IPA relapse during subsequent cytotoxic treatments. Early surgical therapy has not been considered routinely in the management of localized IPA.. Six consecutive patients (four women, two men; median age, 52 years) with localized cavitating IPA diagnosed during chemotherapy-induced aplasia were treated with early surgical resection after hematologic recovery.. All patients received a lobectomy. Surgery was uneventful. This procedures allows patients to proceed with further intensive chemotherapy and/or bone marrow transplantation without IPA reactivation.. For selected patients, surgical resection of localized IPA with unique cavitating lesion, which prevents hemoptysis and IPA recurrence and allows for subsequent cytotoxic treatment, may be recommended.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Female; Follow-Up Studies; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Pneumonectomy; Survival Rate; Time Factors

The use of granulocyte transfusions during amphotericin B treatment of invasive fungal infections in granulocytopenic patients is controversial because of concern about pulmonary complications from leukostasis. Moreover, the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with active infections has been questioned because of reports that this cytokine inhibits neutrophil migration into areas of inflammation. We report a case in which the combined use of amphotericin B, granulocyte transfusions, and GM-CSF was safe and life-saving in a pancytopenic patient with disseminated fusarium infection. Histologic evidence of the migration of neutrophils into an area of active infection was found.

Topics: Agranulocytosis; Amphotericin B; Blood Component Transfusion; Combined Modality Therapy; Fusarium; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Skin

The management of patients with acute leukaemia is often complicated by serious fungal infections, especially of the lungs. The outcome of therapy has historically depended on the early use, efficacy and toxicity of amphotericin B. Pseudoallescheria boydii is an uncommon cause of such infections but as it is more often resistant to amphotericin B early identification may enable the prompt use of alternative and newer antifungal agents. Here we report our experience and review the literature in three cases of P. boydii infection in patients with leukemia, showing unique features such as childhood and central nervous system disease, positive blood cultures and response to itraconazole.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Humans; Itraconazole; Ketoconazole; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudallescheria

Topics: Amphotericin B; Bradycardia; Daunorubicin; Female; Humans; Kidney Neoplasms; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Plasmacytoma

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

Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminated Candida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Candidiasis; Drug Therapy, Combination; Female; Fluconazole; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Neoplasm Recurrence, Local; Recombinant Proteins

Recipients of bone marrow transplants for hematologic malignancies are at risk for a variety of infectious complications. We have reviewed our experience with six patients 2 to 15 years of age who developed significant fungal infections of the lungs before or after bone marrow transplant. No patient was known to have active fungal or bacterial infection at the time bone marrow transplant was performed. In two patients fungal infections were diagnosed before bone marrow transplant, and operations were performed to permit bone marrow transplant under optimal conditions. Four patients had pulmonary mycoses discovered after bone marrow transplant, and underwent operation 12 to 24 days following transplant. Operations consisted of lobectomy (three), multiple unilateral wedge resections (one), staged segmentectomy and contralateral wedge resection (one), and staged bilateral wedge resection (one). Survival following bone marrow transplant was achieved for 6 months and 11 months in patients undergoing lung resection before transplant, and for 24, 30, 39, and 60 days in patients undergoing lung resections after transplant. Bone marrow transplant recipients are at high risk of pulmonary mycoses, and a vigorous search for occult fungal infections should be carried out before transplant. Aggressive operative treatment of fungal infections of the lungs combined with antifungal chemotherapy before transplant may offer the best hope of extended survival.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus; Aspergillus flavus; Bone Marrow Transplantation; Child; Child, Preschool; Female; Fusarium; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma

In the past few years a new syndrome of invasive Candida infection, the so-called hepatosplenic or chronic systemic candidiasis (CSC), has been recognized with increasing frequency in neutropenic patients. From January 1985 to December 1990, ten of 305 acute leukemia (AL) patients treated at our institution were diagnosed as having CSC. In contrast, during the same period this type of Candida infection was not observed in any patient with hematological diseases other than AL treated in our center, including 277 patients who underwent bone marrow transplantation. All patients with CSC had fever and hepatomegaly, and five complained of abdominal pain. Seven patients had neutrophilic leukocytosis and six an increased serum alkaline phosphatase activity. Abdominal computed tomography and ultrasound study showed typical lesions in eight and seven patients, respectively. In four patients a laparoscopy-guided needle liver biopsy displayed yellowish nodules on the liver surface, and the histologic study revealed large granulomas with yeasts and pseudohyphae. All patients were given amphotericin B (mean: 4.6 g, range: 1-12.5 g) and 5-fluorocytosine, and five received fluconazole. No patient died as a direct consequence of CSC and in six the infection resolved. Finally, once controlled, the infectious complication did not preclude subsequent intensive antileukemic therapy, including bone marrow transplantation.

Topics: Adolescent; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Child; Chronic Disease; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome

Topics: Adult; Amphotericin B; Candidiasis; Drug Carriers; Humans; Leukemia, Myeloid, Acute; Liposomes; Liver Abscess; Male

A case of disseminated Scedosporium inflatum infection occurring in a neutropenic patient with acute myeloblastic leukemia is reported. Scedosporium inflatum was isolated from skin lesions, blood, urine and vitreous cultures. Amphotericin B treatment was ineffective in avoiding hematogenous spread. At autopsy, hyphae and ovoid conidia with truncate bases consistent with the morphology of Scedosporium inflatum were found in the lungs, kidneys, myocardium, liver, thyroid, spleen, lymph nodes, brain and the left eye. This is the first report of disseminated Scedosporium inflatum infection and the first time this organism has been isolated from a patient in Europe.

Topics: Aged; Amphotericin B; Humans; Leukemia, Myeloid, Acute; Male; Mitosporic Fungi; Mycoses; Neutropenia; Spain

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

Mucormycosis is a rare infection that occurs in immunocompromised patients. The rhinocerebral form presents in diabetics as a severe necrotizing sinusitis and is not frequent in patients with haematologic malignancies. Diagnosis requires direct examination and culture of biopsy specimens. Two patients with rhinocerebral mucormycosis and haematologic neoplasms (Non-Hodgkin's lymphoma and acute myeloblastic leukaemia) are described. Both patients had severe drug-induced neutropenia when the infection appeared. One patient died in spite of aggressive treatment with surgery and amphotericin.

Topics: Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Myeloid, Acute; Lymphoma, B-Cell; Middle Aged; Mucormycosis; Osteitis; Sinusitis; Skull

Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Eye Enucleation; Eye Infections, Fungal; Fusarium; Humans; Leukemia, Myeloid, Acute; Male; Mycoses

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Appendicitis; Appendix; Aspergillosis; Combined Modality Therapy; Cytarabine; Daunorubicin; Humans; Ileal Diseases; Iliac Vein; Intestinal Perforation; Ischemia; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Neutropenia; Thrombosis

Fungal infections are increasingly being reported in patients with acute leukaemia on intensive induction chemotherapy protocols. The common fungi seen are candida, aspergillus and mucormycosis. We have seen 3 cases of mucormycosis over the last 4 years. All 3 patients had acute leukaemia-two had acute lymphoblastic and one acute myeloid leukaemia. All patients were in neutropenic phase after induction chemotherapy. Features suggestive of fungal infection were fever and development or progression of pulmonary infiltrates despite antibiotic therapy. Repeated body fluid cultures were negative in two patients. In the first patient, the diagnosis was confirmed after biopsy of a palatal mass; he was treated successfully with amphotericin-B. In two patients the diagnosis was confirmed at autopsy. A high degree of suspicion in febrile, neutropenic cancer patients on chemotherapy and early administration of amphotericin-B may improve the outcome. With dissemination, the prognosis is poor.

Topics: Adolescent; Adult; Amphotericin B; Female; Humans; Infusions, Intravenous; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography

A 46-year-old male was admitted to our hospital because of relapse of acute myeloblastic leukemia (M2). Remission was successfully reinduced after reinduction chemotherapy consisting of daunorubicin, cytosine arabinoside, etoposide and vincristine, but was complicated by neutropenia. After the therapy, the patient had persistent fever of about 38 degrees C despite broad-spectrum antibiotics therapy and the patient developed pain in the right quadrant of the abdomen. The white blood cell count rose to 23000/mm3. Liver function tests showed abnormal findings mainly consisting of an elevated serum alkaline phosphatase level. Ultrasonography showed multiple hypoechoic lesions in the liver and CT scans also revealed multiple low density areas. Therefore he was suspected of having a complication of liver abscesses. Amphotericin B was administered 75 mg/day intravenously every other day. A percutaneous liver biopsy was performed, but was not diagnostic. Blood cultures were negative for pathogens. Amphotericin B was administered up to a cumulative dosage of 2.3 g, but the patient remained febrile. Then he had an exploratory laparotomy and an open liver biopsy. The liver biopsy samples showed fungal elements proved by PAS staining. A catheter was inserted into the portal vein. Administration of Amphotericin B was started 20 mg daily through the catheter. The temperature fell to normal after institution of this therapy. The abnormal findings in CT scans almost disappeared and the inflammatory findings became negative after he had received intraportal administration of Amphotericin B over three months. Through the analysis of this case study, we confirmed that the intraportal administration of Amphotericin B was effective to the intractable liver abscesses due to fungi.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liver Abscess; Male; Middle Aged; Mycoses; Neutropenia; Portal Vein; Remission Induction

Two patients with acute leukemia in whom disseminated Trichosporon beigelii infection developed are reported. The T. beigelii infection developed in the first patient while he was receiving 5-fluorocytosine. He was treated with amphotericin B in addition to 5-fluorocytosine. Despite the continued antifungal therapy, multiple organs were invaded by the organisms at autopsy. The second patient was treated with miconazole and norfloxacin. Although this combination antifungal therapy seemed to be effective, this patient required splenectomy for cure of the infection.

Topics: Adult; Amphotericin B; Drug Combinations; Flucytosine; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Miconazole; Mycoses; Norfloxacin; Trichosporon

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Drug Administration Schedule; Drug Therapy, Combination; Flucytosine; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mycoses; Tobramycin; Vancomycin

A patient maintained on long-term immunosuppressive agents after bone marrow transplantation developed an Aspergillus abscess in the right orbit. The abscess was resected without visual compromise and the orbit was irrigated regularly with amphotericin B via an indwelling catheter. Follow-up computed tomography, surgical exploration, and histological analysis demonstrated suppression of fungal growth in the orbit. Persistent fungus was recovered from nonirrigated sinuses despite their previous surgical evacuation and continued systemic amphotericin B administration. Treatment of orbital aspergillosis should include surgical reduction of the local fungal inoculum, supplementation of intravenous antifungal agents with local delivery to minimize systemic toxicity, and attempts to reverse the immunosuppression. If the last is not possible, extensive extirpation of normal surrounding tissues will not prevent repopulation by the ubiquitous fungus.

Topics: Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Catheters, Indwelling; Debridement; Ethmoid Sinusitis; Female; Humans; Immunosuppression Therapy; Injections, Intravenous; Leukemia, Myeloid, Acute; Orbital Diseases

An incidence of up to 30% of systemic fungal infections at autopsy, and difficulties in diagnosing systemic mycosis antemortem, have led to the empiric use of amphotericin B in patients with hematological malignancies. Routine empiric anti-fungal treatment was initiated at our institution in 1982. Amphotericin B and initially for 3 days flucytosine was given to granulocytopenic patients with unremitting (after 48-72 h) or recurrent fever during antibiotic treatment, or with newly detected pulmonary infiltrates, sinusitis, and skin and retinal lesions suggestive of fungal infection. With this approach the rate of systemic fungal infections decreased from 10% to 4% (p less than 0.02). The reduction was most prominent in patients with acute myelogenous leukemia, where fungal infections decreased from 16% to 4% (p less than 0.025).

Topics: Amphotericin B; Creatinine; Drug Therapy, Combination; Flucytosine; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Mycoses; Radiography

A patient with acute myeloid leukemia (AML) who developed probable aspergillosis of the lung underwent partial lobectomy prior to allogeneic bone marrow transplantation (BMT). Diagnosis was proven by microscopic examination of the resected lung tissue. Local and systemic antifungal prophylaxis with oral amphotericin B plus itraconazole was given throughout the immediate post-transplant period and there was no evidence of recurrent mycosis. Fourteen months after BMT the patient is well, in complete remission and leading a normal life. Pre-transplant pulmonary aspergillosis need not therefore be a contraindication to successful BMT.

Topics: Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Female; Humans; Itraconazole; Ketoconazole; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Pneumonectomy

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Candidiasis; Carcinoma, Non-Small-Cell Lung; Female; Humans; Leukemia, Myeloid, Acute; Liposomes; Lung Neoplasms; Male; Middle Aged; Phospholipids; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We prospectively studied the effect of amphotericin B therapy on aminoglycoside clearance in 20 consecutive children during the remission-induction phase of chemotherapy for acute myelocytic leukemia. Increases (greater than 50%) in the half-life for aminoglycoside excretion were not associated with antileukemic or aminoglycoside therapy alone but occurred in 12 of 17 children when amphotericin B was added to the antimicrobial regimen. Seven children had impaired aminoglycoside clearance without increases (greater than 50%) in serum creatinine; hence the resulting adjustments in aminoglycoside dosage would not have been made had we relied solely on serial measurements of serum creatinine. Evidence for increased excretion of the renal enzymes N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase during amphotericin B therapy suggested that damage to proximal tubular cells may contribute to the renal impairment that has been associated with this drug. Our findings underscore the value of monitoring serum aminoglycoside concentrations in children being treated with amphotericin B.

Topics: Acetylglucosaminidase; Adolescent; Aminoglycosides; Aminopeptidases; Amphotericin B; CD13 Antigens; Child; Child, Preschool; Drug Therapy, Combination; Female; Half-Life; Humans; Infant; Kidney Tubules, Proximal; Leukemia, Myeloid, Acute; Male; Monitoring, Physiologic; Prospective Studies

Opportunistic mycotic infections have a significant influence on the morbidity and mortality of children whose immune systems are depressed by the onset of AML. The present paper assesses the incidence of the pathogenic mycotic flora and the in vitro efficacy of the main antimycotic drugs. Candida was che most commonly encountered pathogen and its in vitro response to the polyenic antibiotics was good.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Child; Clotrimazole; Drug Resistance, Microbial; Female; Flucytosine; Humans; Ketoconazole; Leukemia, Myeloid, Acute; Male; Miconazole; Nystatin

In an attempt to decrease the risk for reactivation of life-threatening invasive aspergillosis (IA) during subsequent myelosuppression in patients with previously diagnosed IA who were receiving antileukemic treatment, we evaluated the role of intensive antifungal therapy with amphotericin B and 5-fluorocytosine administered prophylactically throughout the antileukemic regimen and induced granulocytopenia to prevent IA reactivation without compromising the intensive chemotherapy.. During a 30-month period, 10 patients with acute myelogenous leukemia and primary IA developing during initial antileukemia induction therapy and severe granulocytopenia (less than 100/mm3) underwent 14 subsequent courses of intensive marrow aplasia-producing chemotherapy during early complete remission or at leukemia relapse. All patients had evidence of ongoing IA healing by lung computerized tomography (CT) prior to reinstitution of intensive chemotherapy. Nine patients receiving 13 chemotherapy courses also received aggressive prophylactic anti-IA therapy with amphotericin B (1.0 mg/kg/day) and 5-fluorocytosine beginning at least 48 hours prior to antileukemia therapy institution and continued until the time of granulocyte recovery.. All nine patients receiving aggressive antifungal therapy survived without clinical evidence of IA reactivation. Transient radiographic evidence of IA reactivation during granulocytopenia was detected by lung CT during two of the 13 chemotherapy courses. In contrast, the patient who did not receive anti-IA prophylaxis had both clinical and radiographic evidence of IA reactivation during severe granulocytopenia and died. Anti-IA prophylaxis was achieved without irreversible nephrotoxicity, prolonged marrow suppression, alteration of antileukemia treatment, or negative impact on clinical outcome relative to acute leukemia.. This approach of antifungal prophylaxis in adults with acute leukemia and documented primary IA occurring during initial induction chemotherapy has been successful in preventing clinically significant IA reactivation during subsequent granulocytopenic courses, and allows for administration of additional intensive antileukemia therapy.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Drug Therapy, Combination; Flucytosine; Granulocytes; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Middle Aged; Recurrence

Twelve leukemic patients (19%) receiving amphotericin B and aminoglycosides had nephrotoxicity (creatinine value greater than 2.0 mg/dl). Patients with nephrotoxicity tended to be older than patients without nephrotoxicity; gender and total amphotericin B dose were not related to nephrotoxicity. Sodium administration has previously been shown to reverse amphotericin B nephrotoxicity. In this series, among patients receiving ticarcillin at greater than or equal to 18 gm/day (93.6 mEq of sodium per day) the incidence of nephrotoxicity was significantly decreased (1/30, or 3.3%). A multivariate analysis showed that this protective effect of ticarcillin was not dependent on the fact that patients receiving ticarcillin were less likely to receive vancomycin. There were insufficient patients receiving sodium in the absence of ticarcillin to study the effect of sodium alone. However, our observations are consistent with the hypothesis that sodium can prevent renal dysfunction in this clinical situation.

Topics: Adult; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Kidney Diseases; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Sodium; Statistics as Topic; Ticarcillin; Vancomycin

Topics: Amphotericin B; Female; Humans; Iatrogenic Disease; Leukemia, Myeloid, Acute; Meperidine; Opioid-Related Disorders

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

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Topics: Amphotericin B; Blood Urea Nitrogen; Creatinine; Drug Therapy, Combination; Humans; Infusions, Intravenous; Kidney Diseases; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Middle Aged; Mycoses; Penicillins; Risk; Sodium; Ticarcillin

Topics: Agranulocytosis; Amphotericin B; Female; Humans; Ketoconazole; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Neutropenia

Candida krusei infections are increasing in neutropenic patients. This is the first report of a case of C. krusei arthritis in a neutropenic leukemic patient. The organism colonized the patient's respiratory tract and most likely seeded the right knee by hematogenous spread. Knee swelling and tenderness were minimal. Joint fluid Gram stain and fungal smears did not show the organism despite positive results on cultures. With therapy, the joint fluid converted from neutrophilic predominance to lymphocytic predominance. Despite sterilization of knee fluid, clinical relapse occurred after therapy with 256 mg of systemic amphotericin B; the infection was cured after a total dose of 456 mg.

Topics: Adult; Agranulocytosis; Amphotericin B; Arthritis, Infectious; Candida; Candidiasis; Humans; Knee Joint; Leukemia, Myeloid, Acute; Male; Neutropenia

The empirical use of amphotericin B in febrile leukemic patients not responding to antimicrobial agents has previously led to a significant decrease in fatal fungal infections and a significant increase in complete remissions. In this series of 66 patients receiving induction therapy for acute myelogenous leukemia (AML), 49 (74%) received amphotericin B. The median interval between institution of antibiotics and amphotericin B was ten days. Fifteen patients had clinical evidence of fungal infection, but only two (3%) died of fungal infection during induction therapy for AML. We discontinued amphotericin B upon granulocyte recovery (greater than 500/cu mm) unless a pulmonary infiltrate was present. Even though only five of 15 patients with probable fungal infection received more than 1,000 mg of amphotericin B, no patient had recurrent fungal disease while in remission. The incidence of clinically suspected fungal pneumonia during consolidation therapy and reinduction therapy also suggested that our therapy was adequate. An increased incidence of late fungal pneumonia in patients receiving reinduction was associated with prolonged neutropenia (greater than 50 days). This study supports the empirical use of amphotericin B during induction therapy for AML, and suggests that doses can be smaller than those generally recommended for fungal infection.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Cytarabine; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Infusions, Parenteral; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Pneumonia; Retrospective Studies; Time Factors

Topics: Administration, Oral; Adult; Amphotericin B; Candidiasis; Female; Humans; Leukemia, Myeloid, Acute; Liver Abscess

The toxic effects of the combinations of amphotericin B (AmB) and actinomycin D or AmB and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea were measured against the human promyelocytic leukemia cells HL-60. The toxicities of both drug combinations were greater than the additive toxicity of each of the drugs used singly, but the exact conditions under which synergism was achieved differed for each combination. The synergism achieved by the AmB-actinomycin combination was accompanied by an AmB-induced increase in uptake of actinomycin D by the HL-60 cells, whereas the synergism of the AmB-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea combination could be linked to potentiation by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea of AmB-induced oxidative injury. These results indicate that the synergism of these two drug combinations was caused by different mechanisms.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cell Count; Cell Line; Dactinomycin; Drug Synergism; Humans; L-Lactate Dehydrogenase; Leukemia, Myeloid, Acute; Lomustine; Malondialdehyde; Oxidation-Reduction; Potassium; Thymidine

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Candidiasis; Drug Resistance, Microbial; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged

Aureobasidium pullulans, a conidial fungus widely distributed in the environment, was repeatedly isolated from the blood of a 28-year-old man with acute myeloid leukaemia. Amphotericin B failed to eliminate the organism.

Topics: Adult; Amphotericin B; Humans; Leukemia, Myeloid, Acute; Male; Mitosporic Fungi; Mycoses

We use murine erythroid Friend cells and human promyelocytic HL60 cells to investigate the influence of a transmembrane signal in triggering myeloid or erythroid cell differentiation. Combined treatments were given with dimethylsulfoxide, actinomycin D and amphotericin B, a substance which resembles a deviant membrane lipid and which seems to influence exclusively membrane activity. Our results suggest that a membrane modification alone is sufficient for in vitro HL60 cell differentiation, whereas both a transmembrane and a nuclear signal are necessary for Friend cell differentiation.

Topics: Amphotericin B; Cell Differentiation; Cell Division; Cell Line; Dactinomycin; Dimethyl Sulfoxide; Drug Synergism; Friend murine leukemia virus; Humans; Kinetics; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Liver Abscess; Male; Mercaptopurine; Portal System; Prednisolone

A young woman with acute myelocytic leukemia developed acute lower gastrointestinal bleeding immediately after a first remission induction of her leukemia. After the site of bleeding was located in the descending colon, a necrotic bleeding ulcer was resected. Histologic examination of the ulcer established the diagnosis of gastrointestinal mucormycosis. Treatment with amphotericin B was administered because of the high risk of dissemination. The patient has been followed for 9 months with no evidence of relapse of infection. Survival after gastrointestinal mucormycosis in acute leukemia has not previously been reported in the English language literature. Success in managing mucormycosis depends on the adherence to the recommended principles of early aggressive diagnostic measures, excisional surgery, amphotericin B therapy, and control of the underlying predisposing condition.

Topics: Adult; Amphotericin B; Female; Gastrointestinal Hemorrhage; Humans; Leukemia, Myeloid, Acute; Mucormycosis

We describe a patient with acute leukemia who developed a primary aspergilloma. A combination of surgical resection and parenteral amphotericin B cured the lesion. The pathophysiology, diagnosis and treatment of primary pulmonary aspergilloma are reviewed.

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Female; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Pneumonectomy

We report a cluster of primary cutaneous aspergillosis in six children with hematologic malignancy. When first seen, they had hemorrhagic bullae caused by Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger at the sites of insertion of intravenous cannulas or where arm boards had been taped to the extremities. Rapid diagnosis of cutaneous aspergillosis was made by direct examination of the blister roof with potassium hydroxide before it progressed to a necrotic ulcer. Intravenous amphotericin was instituted promptly in five of six patients, and none died of disseminated aspergillosis. Epidemiologic investigation tracked the source of aspergillus to a storeroom with a false ceiling that had recently been repaired for a water leak.

Topics: Amphotericin B; Aspergillosis; Aspergillus; Child; Child, Preschool; Cross Infection; Dermatomycoses; Equipment Contamination; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Materials Management, Hospital

A case of septic, histoplasmal monoarthritis of the knee in a leukaemic patient is described. Ketoconazole therapy failed to eliminate the infection, but after histoplasmosis was diagnosed prolonged therapy with amphotericin B was curative.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Histoplasmosis; Humans; Knee Joint; Leukemia, Myeloid, Acute; Male

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.

Topics: Acyclovir; Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Child; Cyclophosphamide; Etoposide; Female; Graft Survival; Graft vs Host Disease; Herpes Genitalis; HLA Antigens; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Methotrexate; Middle Aged; Nystatin; Prednisolone; Tissue Donors; Whole-Body Irradiation

Invasive fungal disease continues to be a significant problem among immunocompromised patients. We report a case of systemic Rhodotorula infection in a patient with acute myelogenous leukaemia. Rhodotorula was isolated from bone marrow on two separate occasions despite initial treatment with amphotericin B. Liver computerised tomographic scan suggested liver abscesses, and yeasts were seen on biopsy. The patient survived after aggressive antifungal and antileukaemia treatment. Rhodotorula fungaemia has been occasionally associated with shock. As our case illustrates, Rhodoturola may be a cause of invasive fungal disease in the immunocompromised host but can be eradicated if treated aggressively.

Topics: Adult; Amphotericin B; Bone Marrow; Flucytosine; Humans; Ketoconazole; Leukemia, Myeloid, Acute; Liver Abscess; Male; Mitosporic Fungi; Mycoses; Rhodotorula

Fulminant Aspergillus sinusitis is a disease of immunocompromised hosts strongly associated with neutropenia. A case of sinusitis due to Aspergillus flavus that developed in a patient with acute leukemia during the third week of treatment with amphotericin B is described. Indium 111-labeled white blood cell scanning demonstrated uptake of granulocytes into the involved sinuses. Thereafter, use of granulocyte transfusions was associated with stabilization of the patient's clinical course.

Topics: Amphotericin B; Aspergillosis; Aspergillus flavus; Blood Transfusion; Female; Granulocytes; Humans; Leukemia, Myeloid, Acute; Middle Aged; Paranasal Sinuses; Sinusitis

Hepatotoxicity is regarded as a rare side effect of amphotericin B therapy. A patient with acute myelogenous leukemia who had normal liver function was treated with amphotericin B for fungal pneumonia. While he was receiving the drug at high dosages asymptomatic elevation of the levels of alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase and bilirubin was noted. The levels returned to normal when the drug was discontinued. Rechallenge with a lower dosage prompted a rapid rise in the levels, with subsequent return to normal when the medication was withdrawn.

Topics: Amphotericin B; Chemical and Drug Induced Liver Injury; Cytarabine; Humans; Leukemia, Myeloid, Acute; Liver; Male; Middle Aged; Mycoses; Pneumonia; Thioguanine

Topics: Adult; Amphotericin B; Aspergillosis; Humans; Klinefelter Syndrome; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Pulmonary Embolism

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

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

A retrospective evaluation was made on the value of amphotericin B lozenges in the selective elimination of yeasts from the oropharynx. Four different groups of severely granulocytopenic patients were studied. All 77 patients received amphotericin B orally as a suspension or as tablets. Four amphotericin B lozenges were also administered daily for topical antimycotic decontamination of the oropharynx. This was done in the presence of colonization-resistance decreasing factors such as a nasogastric tube (Group I, 19 patients) or mucosal damage (Group III, 25 patients) and in patients with four or more consecutive throat swab cultures with yeasts (Group IV, 11 patients). The 22 patients in Group II did not receive lozenges. The addition of lozenges resulted in a decrease in the mean "growth density" of Candida cells in the oropharynx. This reduction was significant in Group III (p less than 0.01) and Group IV (p less than 0.02) and became evident during the first week of treatment. In patients with a nasogastric tube, however, 51.8% of the throat swab cultures revealed yeasts. Increasing the dose of the lozenges might improve the results in these patients. Topical treatment of the oropharynx with amphotericin B lozenges is advocated for patients who are susceptible to Candida infections.

Topics: Amphotericin B; Candida; Candidiasis, Oral; Dosage Forms; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Neutropenia; Oropharynx; Retrospective Studies

Topics: Agranulocytosis; Amphotericin B; Cytarabine; Daunorubicin; Decision Making; Esophagitis; Fever of Unknown Origin; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses

Two additional cases of systemic mycosis due to Trichosporon cutaneum are reported and are compared with the previously published case of Rivera and Cangir. Both patients (a four-year-old male and a 57-year-old female) had acute leukemia for which they were receiving chemotherapy, and both presented with fever that was unresponsive to conventional antibiotics. Both had positive blood cultures for Trichosporon cutaneum. The disease was further documented in the four-year-old male by renal biopsy and by bone marrow culture; he was treated with apparent success with amphotericin B. However, the 57-year-old female died shortly after the begining of similar treatment, and autopsy demonstrated involvement of the left kidney, spleen, bone marrow, and liver. The organism in both these cases, as well as the case of Rivera and Cangir, exhibited both hyphal and yeastlike forms in tissue sections. We believe that the therapeutic success in the case of the four-year-old male was primarily related to his remission from leukemia.

Topics: Amphotericin B; Child, Preschool; Female; Humans; Kidney; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycoses; Yeasts

A 67-year old man with acute myelomonocytic leukemia had Candida albicans fungemia during induction chemotherapy. Bilateral pulmonary infiltrates and hepatic granulomata containing yeast forms and septate hyphae developed, but cultures of the hepatic tissue failed to grow a fungus. Although his pulmonary and liver disease improved following appropriate therapy, vertebral osteomyelitis due to Candida albicans developed approximately 12-15 weeks after the original fungemia. The fungal osteomyelitis was successfully treated with amphotericin B and 5-fluorocytosine. This case illustrates the need for early diagnosis and aggressive treatment of fungal infections in patients with leukemia.

Topics: Aged; Amphotericin B; Candidiasis; Flucytosine; Humans; Intervertebral Disc; Leukemia, Myeloid, Acute; Lumbar Vertebrae; Male; Osteomyelitis; Radiography; Spinal Diseases

Candida lusitaniae associated with infection in a patient with acute myelogenous leukemia developed resistance to amphotericin B during systemic treatment of the patient. The organism, when isolated initially, was inhibited by 0.31 mug of amphotericin B per ml in yeast nitrogen base agar, but when isolated (20 days later) just antemortem and postmortem, required 100 and 50 mug/ml, respectively, for complete inhibition at 48 h.

Topics: Amphotericin B; Candidiasis; Drug Resistance, Microbial; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged

Seven patients with metastatic tumors resistant to therapy with adriamycin, BCNU, plus cyclophosphamide received the same chemotherapy combined with amphotericin B. One complete response (acute myelomonocytic leukemia), two partial responses (carcinoma of the breast and multiple myeloma), and one case with objective improvement (carcinoma of the breast) were observed in seven evaluable trials. Myelosuppression was not consistently changed by addition of amphotericin B. Fever and chills were common after amphotericin B. Bronchospasm and hypotension occurred twice. Amphotericin B reverses resistance to adriamycin-containing chemotherapy regimens in some patients.

Topics: Adult; Aged; Amphotericin B; Breast Neoplasms; Carmustine; Cyclophosphamide; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Multiple Myeloma; Neoplasms

The administration of a low total dose of amphotericin B to four consecutive patients already receiving gentamicin resulted in a deterioration of renal function in all. No other cause of the renal dysfunction was apparent in three cases. It appears probable that these drugs exhibit synergistic nephrotoxicity.

Topics: Aged; Amphotericin B; Drug Therapy, Combination; Female; Gentamicins; Humans; Kidney; Leukemia, Myeloid, Acute; Male; Middle Aged; Nephritis

Pulmonary aspergillosis developed in a 62-year-old man with acute myelogenous leukemia. Therapy with amphotericin B and 5-fluorocytosine was begun. Synergy between amphotericin B and rifampin was demonstrated in vitro, and therapy with firampin replaced 5-fluorocytosine. Progressive clearing of the pulmonary lesion ensued, suggesting in vivo efficacy as well. Further studies of patients utilizing this regimen are warranted.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Drug Synergism; Flucytosine; Humans; In Vitro Techniques; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Radiography; Rifampin

The diagnosis and successful control of systemic Aspergillus niger infection in 2 adult patients with acute leukemia is reported. During induction therapy, the first patient developed pulmonary infiltrates, skin lesions and abnormal liver function tests. Aspergillus niger was found on skin and liver biopsy. This patient was successfully treated with Amphotericin B and granulocyte transfusions and he remains in remission. The second patient developed a pneumonitis and adynamic ileus with positive sputum and stool cultures for Aspergillus niger. The infection only responded to Amphotericin B and granulocyte transfusions and the leukemia to cytoreductive chemotherapy. The patient later relapsed and died after a febrile illness. Fungi morpholocially consistent with Aspergillus were found in the liver at autopsy. Infection with A. niger is rare even in this patient population; however fungal infections have become an increasing problem. The need for a high index of suspicion, especially when an infection is unresponsive to antibacterial antibiotics, the various diagnostic tools, and the need for aggressive therapy are stressed. Amphotericin B is the chemotherapy of choice but may be insufficient in a severely neutropenic host where the simultaneous use of granulocyte transfusions might be lifesaving.

Topics: Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Aspergillosis; Aspergillus; Aspergillus niger; Blood Transfusion; Female; Granulocytes; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Myeloid, Acute; Leukocytes; Male; Sputum

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Autopsy; Biopsy; Candidiasis; Candidiasis, Oral; Child, Preschool; Female; Fever of Unknown Origin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Mucor; Mycoses; Retrospective Studies

Topics: Adult; Amphotericin B; Candidiasis; Candidiasis, Oral; Exudates and Transudates; Flucytosine; Humans; Immunosuppression Therapy; Leukemia, Myeloid, Acute; Male; Retinitis

Topics: Adult; Agglutination Tests; Amphotericin B; Anti-Bacterial Agents; Candida; Candidiasis; Child; Cyclophosphamide; Cytarabine; Evaluation Studies as Topic; False Negative Reactions; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Nitrosourea Compounds; Precipitin Tests; Prednisone; Serologic Tests; Vinblastine; Vincristine

Topics: Acute Disease; Adult; Amphotericin B; Blood Cell Count; Blood Platelets; Candida; Candidiasis; Cytarabine; Feces; Fever; Humans; Hypersplenism; Leukemia; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Nose; Pharynx; Prednisone; Skin; Spleen

Topics: Amphotericin B; Candida; Candidiasis; Humans; Leukemia, Myeloid, Acute; Lung Abscess; Lung Diseases, Fungal; Male; Middle Aged; Pneumothorax

Topics: Adrenal Cortex Hormones; Adult; Aged; Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Female; Histoplasmosis; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged