amphotericin-b and Anemia--Aplastic

Invasive fungal disease is a serious infectious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Exserohilum rostratum is a species causing phaeohyphomycosis, which rarely causes invasive disease in humans. We treated a case of sinusitis caused by E. rostratum after cord blood transplantation (CBT). A 60-year-old man with myelodysplastic syndrome, who had a medical history of an operation to correct deviation of the nasal septum, developed sinusitis caused by E. rostratum under prolonged profound neutropenia after a second CBT because of the graft rejection of the first transplantation. Liposomal amphotericin B improved the sinusitis. A literature review revealed nine reported cases of sinusitis caused by E. rostratum, including our case. Although five cases had severe neutropenia at onset (HSCT recipients, n = 2; aplastic anemia, n = 3), the remaining four had no preexisting immunosuppressive conditions. However, three of the four patients had preexisting nasal diseases with or without a history of surgery, as in our case. Excluding our case, the outcome was fatal in five neutropenic patients, whereas the four patients without neutropenia recovered. Although sinusitis caused by E. rostratum is rare, E. rostratum should be recognized as a possible pathogen causing sinusitis in highly immunosuppressed patients such as HSCT recipients. Preexisting nasal disease and/or nasal surgery could be risks for this infection.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Ascomycota; Bone Marrow Transplantation; Child; Child, Preschool; Female; Fetal Blood; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Middle Aged; Mycoses; Myelodysplastic Syndromes; Neutropenia; Sinusitis; Young Adult

Invasive fungal infections often occur in immunocompromised patients. Here, we report an infection case caused by Geotrichum capitatum in a severe aplastic anemia patient.. Identification of the pathogenic bacteria was done by sequencing and mass spectrometric analysis.. The fungal infection was isolated from blood cultures. The pathogenic bacteria were identified as Geotrichum capitatum. The infection was primarily cured by voriconazole and caspofungin monotherapy. However, the effect was not obvious. Then a combination of liposomal amphotericin B and caspofungin was used. Body temperature of the patient decreased, and clinical symptoms improved.. Sequencing and mass spectrometric analysis could have a role for Geotrichum capitatum diagnosis. Curative effect of using a single antifungal drug was unsatisfactory. Using liposome amphotericin B combined with caspofungin might obtain certain curative effect. Early diagnosis and appropriate combined therapy were necessary to improve the outcome of patients with Geotrichum capitatum infection.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Caspofungin; Drug Therapy, Combination; Female; Geotrichum; Humans; Mycoses; Severity of Illness Index; Voriconazole

Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review.. We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included. Demographics, treatment and outcomes were analyzed using R Gui statistical software.. Twelve studies met inclusion criteria (103 patients). There was male preponderance of 48.5% with median age of 11 years old. Majority of patients had underlying leukemia (44.6%). Aspergillus was the predominant organism (47%). Isolated nasal findings occurred in 14% of patients and nasal findings occurred in 49% overall. Absolute neutrophil count (ANC) of immunocompromised patients was below 600 in most patients (99%). Average and median length of neutropenia was 2 weeks. All patients were prescribed amphoterocin with 50% as single medicinal therapy. Surgery occurred in 82.8% of cases. The mortality rate was 46%. Univariate analysis identified presenting with facial pain as a negative predictor of overall mortality (OR 0.296, 95% CI: 0.104-0.843, p < 0.05).. Mortality remains high in pediatric patients with IFS. An ANC of <600 occurred in the majority of immunocompromised patients at a duration of 2 weeks. Presenting with facial pain was a negative predictor of mortality. Many studies label this condition as invasive fungal sinusitis; however, approximately one seventh presented with only nasal findings and half overall had nasal involvement.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Burkitt Lymphoma; Candidiasis, Invasive; Child; Facial Pain; Female; Fusariosis; Humans; Immunocompromised Host; Leukemia; Male; Mucormycosis; Mycoses; Neutropenia; Otorhinolaryngologic Surgical Procedures; Prognosis; Retrospective Studies; Sinusitis

Opportunistic mycoses have emerged as important causes for morbidity and mortality in pediatric cancer patients, particularly in those with intensively treated hematological malignancies, allogeneic hematopoetic stem cell transplantation, and aplastic anemia. The incidence of invasive fungal infections in these settings may range from 10 to 25 % despite empirical antifungal therapy with an overall case fatality rate of up to 50 and 75 % depending on the organism. Preventive interventions are thus warranted, including but not limited to chemoprophylaxis with antifungal agents. Effective chemoprophylaxis of invasive Candida infections with a long-term benefit for overall survival has been demonstrated in patients with allogeneic bone marrow transplantation. However, its benefit in other high-risk populations is less well established, and a clearly effective approach to chemoprophylaxis for invasive Aspergillus infections has not been documented in appropriately designed clinical trials. This article reviews epidemiology and current approaches to chemoprophylaxis of opportunistic invasive fungal infections in children and adolescents with cancer and/or stem cell transplantation, and provides evidence-based guidelines for indications and modalities of antifungal prophylaxis and antifungal infection control measures in this population.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Cohort Studies; Double-Blind Method; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Infant, Newborn; Itraconazole; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; Respiratory Therapy; Risk Factors; Time Factors

Trichoderma longibrachiatum infection of the skin in an 11-year-old child with severe aplastic anemia and prolonged neutropenia is reported. The patient received systemic antifungal therapy and underwent bone marrow transplantation. To our knowledge, this is the first description of T. longibrachiatum infection in a pediatric patient. It also is the first case successfully treated with medical therapy. A review of the literature suggests that Trichoderma spp. are recognized as human pathogens with increasing frequency, particularly for immunocompromised patients, and should be considered in the differential diagnosis of fungal infections in the pediatric population.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Child; Dermatomycoses; Humans; Male; Skin; Trichoderma

Invasive fungal sinusitis is becoming increasingly common in patients undergoing BMT. This study was undertaken to evaluate the incidence, presenting symptoms, diagnosis procedures, treatment and outcome of invasive fungal sinusitis. The study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eleven patients (2.6%) developed invasive fungal sinusitis, 8 had underlying hematologic malignancies and 3 severe aplastic anemia (SAA). Median interval between BMT and fungal sinusitis was 22.5 days (range 2-106 days). Eight of 11 patients had protracted neutropenia (median 8 days with median neutrophil count at the time of fungal sinusitis diagnosis of 0.25 x 10(9)/l). Four patients developed GVHD before fungal sinusitis was diagnosed. Presenting symptoms were fever (100%), orbital swelling (63%), facial pain (54%) and nasal congestion (36%). In 8 patients Aspergillus species were isolated (A. flavus in 7, A. quadrilineatus in 1); in 1 patient Candida albicans was isolated and in the other 2 fungal elements were detected histologically (Fusarium and Mucor, respectively). Six of the patients underwent surgical debridement at diagnosis. Three received granulocyte transfusions. All patients received systemic amphotericin B (7 conventional and 4 amphotericin B colloidal dispersion (ABCD)). Only 2 of the 11 patients responded completely to therapy with a follow-up of 15 months. It appears that invasive fungal sinusitis is a potentially fatal complication in immunocompromised patients post-BMT. Current treatment approaches are largely ineffective and new methods of management of this serious problem are needed.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Purging; Bone Marrow Transplantation; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Debridement; Drainage; Female; Follow-Up Studies; Graft vs Host Disease; Granulocytes; Humans; Immunocompromised Host; Incidence; Infant; Leukemia; Leukocyte Transfusion; Lymphoma; Male; Middle Aged; Mitosporic Fungi; Mycoses; Neutropenia; Sinusitis; Survival Rate; Treatment Outcome

Cunninghamella bertholletiae is a fungus of the Zygomycetes class, Mucorales order. Only very few cases of disseminated infection have been reported. We observed a new case in a 19 years old man with severe aplastic anemia, due to pulmonary primoinfection and hematologic dissemination. This aplastic anemia failed to respond first to an antithymocyte globulin and steroid treatment and then to cyclosporine A. Deferoxamine was infused weekly to prevent iron overload. During a second antithymocyte globulin and steroid treatment, the patient developed bilateral pneumonia. Culture of the broncho-alveolar washing fluid established the diagnosis by isolation of C. bertholletiae. Despite amphotericin B and 5-fluorocytosine intravenous therapy, the patient died of disseminated infection six days after diagnosis, which was confirmed by necropsy. Underlying conditions, diagnosis and treatment are discussed, together with a review of the literature.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Flucytosine; Humans; Immunocompromised Host; Lung Diseases, Fungal; Male; Mucorales; Mucormycosis; Opportunistic Infections

Topics: Administration, Topical; Amphotericin B; Anemia, Aplastic; Anti-Infective Agents; Benzamidines; Chronic Disease; Conjunctivitis; Conjunctivitis, Allergic; Corneal Injuries; Dermatitis, Contact; Drug Eruptions; Epithelium; Humans; Idoxuridine; Keratitis; Stevens-Johnson Syndrome; Sulfonamides; Wound Healing

Topics: Aminoglycosides; Amphotericin B; Anemia, Aplastic; Bacterial Infections; Bone Marrow Transplantation; Graft Survival; Graft vs Host Disease; Humans; Immunosuppression Therapy; Leukemia; Mycoses; Patient Isolation; Postoperative Complications; Sulfamethoxazole; Time Factors; Trimethoprim; Virus Diseases

Topics: Amphotericin B; Anemia, Aplastic; Animals; Anti-Bacterial Agents; Antitubercular Agents; Bone Marrow; Bone Marrow Diseases; Chloramphenicol; Humans; In Vitro Techniques; Mice; Rabbits; Ristocetin; RNA; Tetracycline

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibody Specificity; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; False Positive Reactions; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Hepatitis; Humans; Liposomes; Male; Middle Aged; Neutropenia; Patient Isolation; Predictive Value of Tests; Sensitivity and Specificity

Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Enzyme-Linked Immunosorbent Assay; False Negative Reactions; Female; Fungemia; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Transplantation Conditioning; Transplantation, Homologous

Invasive aspergillosis is a life-threatening fungal infection which, in neutropenic patients, is associated with an extremely high mortality rate despite optimal treatment. In order to investigate microbiological risk factors for treatment failures in more detail, Aspergillus spp. obtained from 29 patients with haematological diseases after myelo-ablative chemotherapy and bone marrow transplantation were analysed for their susceptibility to amphotericin B in vitro and this was compared with clinical outcome to see if there was a correlation. Aspergillus flavus was present in 12 (41 %) of the 29 patients, Aspergillus terreus in nine (31%) and Aspergillus fumigatus in eight (28%). The susceptibility of these isolates to amphotericin B varied between and within the three species. A. terreus was the only organism against which the MIC was consistently high, A. fumigatus and A. flavus showing variation between isolates in the degree of resistance to amphotericin B. The degree of in-vitro resistance was the only parameter correlating with clinical outcome in a univariate analysis and the only prognostic value in a multivariate analysis considering known risk factors. Irrespective of the species, all six patients with isolates against which the MIC was <2 mg/L survived, whereas most (22/23) of those with isolates resistant to > or = 2 mg/L died. Infections among the six survivors were caused by amphotericin B-susceptible A. fumigatus and A. flavus, but not A. terreus. We conclude that the outcome of aspergillus infection depends on the in-vitro susceptibility of the isolates to amphotericin B. Survival was poor in patients with isolates resistant to amphotericin B and good in those with amphotericin B-susceptible specimens. A. terreus was always associated with high resistance to amphotericin B and with poor survival.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Aspergillus; Burkitt Lymphoma; Cells, Cultured; Humans; Leukemia; Microbial Sensitivity Tests; Multiple Myeloma; Multivariate Analysis; Predictive Value of Tests; Prognosis; Risk Factors; Treatment Outcome

Topics: Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Candidiasis; Female; Humans; Incidence; Leukemia; Liposomes; Male; Metabolic Diseases; Neoplasms; Transplantation, Autologous; Transplantation, Homologous

Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection-related mortality in patients with haematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (eg neutropenic vs non-neutropenic patients). Diagnosis is particularly challenging in patients receiving mould-active prophylactic or empirical treatment, which reduces the sensitivity of all diagnostic tests for IPA. Second, treatment of IPA is complex due to unpredictable pharmacokinetic profiles of antifungal agents, small therapeutic window in terms of exposure and adverse events, and multiple drug-drug interactions through the CYP450 system. Here we report a case of a 23-year-old male with severe aplastic anaemia and subpleural nodules. Diagnostic tests for IPA obtained during ongoing mould-active empirical treatment were negative. Intravenous voriconazole was stopped after visual disturbances and hallucinations. The patient then had an anaphylactic reaction to liposomal amphotericin B and was switched to intravenous posaconazole, which had to be discontinued due to a significant increase in transaminase levels. He was treated with oral isavuconazole with reduced dosage, triggered by increasing transaminases under the standard dosage. Even under reduced dosage, blood concentrations of isavuconazole were high and treatment was successful. The case illustrates real-world challenges and unmet needs in the diagnosis and treatment of IPA in patients with haematological diseases.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillus; Hematologic Diseases; Humans; Invasive Pulmonary Aspergillosis; Male; Neutropenia; Nitriles; Pyridines; Transaminases; Treatment Outcome; Triazoles; Voriconazole; Young Adult

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

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

Aspergillus and Candida species are the main causative agents of invasive fungal infections in immunocompromised human hosts. However, saprophytic fungi are now increasingly being recognized as serious pathogens. Trichoderma longibrachiatum has recently been described as an emerging pathogen in immunocompromised patients. We herein report a case of isolated suspected invasive pulmonary infection with T. longibrachiatum in a 29-year-old man with severe aplastic anemia who underwent allogeneic stem cell transplantation. A direct microscopic examination of sputum, bronchoaspiration, and bronchoalveolar lavage fluid samples revealed the presence of fungal septate hyphae. The infection was successfully treated with 1 mg/kg/day liposomal amphotericin B.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lung Diseases, Fungal; Male; Opportunistic Infections; Trichoderma

A patient with aplastic anaemia, successively treated with caspofungin then liposomal amphotericin, developed a disseminated infection due to Acremonium, further confirmed as resistant in vitro to these drugs. Successful treatment was achieved with voriconazole. Multiple antifungal treatments may expose to the risk of breakthrough of multi-resistant pathogens in haematology patients.

Topics: Acremonium; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Male; Mycoses; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

Mucormycosis is a rare but aggressive fungal infection that predominantly affects immunocompromised patients. We report a case that highlights the importance of knowledge to enable prompt diagnosis and management of an otherwise fatal phenomenon.

Topics: Aged, 80 and over; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Escherichia coli Infections; Fatal Outcome; Female; Humans; Immunocompromised Host; Mucormycosis; Necrosis; Rhizopus; Tongue; Triazoles

Mucormycosis is associated with a variety of immunocompromised hematological conditions, especially hematological malignancies. The common presentations include rhino-cerebral, pulmonary and disseminated types. However, occurrence of renal mucormycosis in aplastic anemia is rare. We describe the case of a 20-year-old man with such a rare association.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Cyclosporine; Humans; Immunosuppressive Agents; Male; Mucormycosis; Renal Dialysis; Steroids; Young Adult

Topics: Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Common Variable Immunodeficiency; Echinocandins; Fatal Outcome; Female; Fungal Proteins; Humans; Immunocompromised Host; Lung Diseases, Fungal; Mucormycosis; Rhizopus; Treatment Failure

Matched sibling donor hematopoietic stem cell transplantation is the standard of care for severe aplastic anemia, with an overall survival of 80% to 90%. Only 60% to 70% of patients respond to treatment with immunosuppressive therapy. The main life threatening complications are infections, graft failure, and graft versus host disease. A 10-year-old patient with severe aplastic anemia underwent matched sibling donor hematopoietic stem cell transplantation, but developed sudden onset of fatal multiorgan failure on day +12. The cause of death was found only after autopsy.

Topics: Amphotericin B; Anemia, Aplastic; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Mucormycosis; Multiple Organ Failure; Pyrimidines; Rhizomucor; Triazoles; Voriconazole

Infectious mononucleosis (IM) is a rare cause of aplastic anemia in adults. We report of a patient in whom aplastic anemia, mucormycosis and aspergillosis complicated during the course of IM and successfully treated with liposomal amphotericin B. According to our searches in literature, we could not find a similar patient complicated and successfully treated like ours.

Topics: Amphotericin B; Anemia, Aplastic; Aspergillosis; Female; Humans; Infectious Mononucleosis; Middle Aged; Mucormycosis; Necrosis; Paranasal Sinuses; Tomography, X-Ray Computed; Treatment Outcome

A 38-year-old Japanese man with severe aplastic anemia had invasive pulmonary aspergillosis as a complication. He was treated with amphotericin B for six weeks, but the aspergillosis did not improve. Then he experienced a fatal myocardial infarction. An autopsy revealed disseminated aspergillosis involving pericarditis and Aspergillus embolization to the coronary arteries. This led to the acute myocardial infarction. Cardiac aspergillosis is rare, but should be included within the differential diagnosis when chest pain of unknown origin occurs in an immunosuppressed patient.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Coronary Disease; Embolism; Humans; Immunocompromised Host; Lung Diseases, Fungal; Male; Myocardial Infarction; Pericarditis

Invasive aspergillosis seems to be on the rise, especially in immunocompromised children. Historically, only systemic amphotericin B has been effective against Aspergillus. Development of newer antifungal agents, such as voriconazole and caspofungin, has improved the treatment options available for aspergillosis, although no definitive management strategy has been established. Here we describe the use of topical voriconazole combined with systemic antifungal agents for cutaneous aspergillosis in a pediatric patient after bone marrow transplant.

Topics: Administration, Cutaneous; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Aspergillus flavus; Bone Marrow Transplantation; Combined Modality Therapy; Debridement; Dermatomycoses; Disease Susceptibility; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Injections, Subcutaneous; Nystatin; Postoperative Complications; Pyrimidines; Skin; Transplantation, Homologous; Triazoles; Voriconazole

The emergence of new antifungal compounds with alternative mechanisms of action and improved tolerability has opened up new therapeutic possibilities for the use of combined antifungal treatment in life-threatening systemic fungal infections. A case report of an 8-year-old allogeneic stem cell transplant recipient who developed a central venous catheter tunnel infection caused by Aspergillus flavus is presented here. In spite of conventional and subsequent liposomal amphotericin B therapy the infection progressed rapidly and the necrosis extended further to the thoracic wall, pleura and the right lung. Combined treatment consisting of liposomal amphotericin B and caspofungin was instituted. After 30 days of dual therapy the deep fungal infection resolved and the extensive soft tissue defect showed scarring. One year post-transplant, the patient is well, with normal bone marrow function and full donor chimerism. Although there is limited clinical data on the effectiveness of echinocandins in pediatric patients with documented invasive fungal infections, this case report shows that combining liposomal amphotericin B with caspofungin could be advantageous.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Aspergillus flavus; Bone Marrow Transplantation; Caspofungin; Catheterization, Central Venous; Child; Cicatrix; Disease Progression; Drug Synergism; Drug Therapy, Combination; Echinocandins; Equipment Contamination; Female; Hepatitis; Humans; Immunocompromised Host; Leukocyte Transfusion; Lipopeptides; Liposomes; Necrosis; Peptides, Cyclic; Pneumothorax; Postoperative Complications; Remission Induction; Salvage Therapy; Torque teno virus; Transplantation, Homologous

We report on a 10-year-old girl with severe aplastic anaemia who developed rhinocerebral infection caused by Absidia corymbifera and a possible co-infection caused by Alternaria alternata. Despite prolonged neutropenia, therapy with liposomal amphotericin B and posaconazole improved the clinical condition. Subsequently, the girl underwent allogeneic haematopoietic stem cell transplantation (HSCT) for the underlying disease, but the fungal infection remained under control with the antifungal treatment. No severe side effect of the antifungal drugs was noted. Unfortunately, the girl died 5 months after HSCT due to disseminated adenovirus infection.

Topics: Absidia; Alternaria; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Central Nervous System Fungal Infections; Child; Female; Humans; Radiography; Sinusitis; Stem Cell Transplantation; Telencephalon; Transplantation, Homologous; Triazoles; Zygomycosis

Native valve fungal endocarditis is an uncommon disease with a high mortality rate. We present the clinical features, histological findings and outcome of 2 patients with native valve Aspergillus endocarditis. Both patients had aplastic anaemia as a predisposing disease. The diagnosis was made by Duke's criteria in 1 case and by histology in the other. Surgery was precluded owing to profound thrombocytopenia. Both patients had fatal outcome despite administration of liposomal amphotericin beta.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Caspofungin; Echinocandins; Endocarditis; Fatal Outcome; Female; Humans; Itraconazole; Lipopeptides; Male; Peptides, Cyclic

An allogeneic stem cell transplant recipient developed pulmonary infiltrates and Aspergillus antigenemia during prophylactic low-dose liposomal amphotericin B. No response to therapy was observed after increasing the dose of liposomal amphotericin B and addition of caspofungin, and breakthrough candidemia developed. Therapy switch to voriconazole did not prevent the development of lethal septic shock. Shortly before death, Scopulariopsis brevicaulis was cultured from bronchial secretions, and positive blood cultures demonstrated persistent candidemia due to Debaryomyces hansenii, teleomorph of Candida famata.

Topics: Aged; Amphotericin B; Anemia, Aplastic; Ascomycota; Aspergillosis; Body Fluids; Caspofungin; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Male; Mycoses; Peptides, Cyclic; Pyrimidines; Saccharomycetales; Shock, Septic; Triazoles; Voriconazole

Voriconazole is a new triazole active orally and parenterally that recently proved effective in the treatment of invasive aspergillosis and in empirical antifungal therapy for persistently febrile neutropenic patients. Limited data are available for pediatric patients. We report our experience with voriconazole in seven children with invasive aspergillosis, i.e., four girls and three boys with a median age of 5 (range 2-13) years affected by acute lymphoblastic leukemia (3), acute myeloid leukemia (2), refractory anemia with excess of blasts (1), and severe aplastic anemia (1). First-line therapy in all patients was liposomal amphotericin B (AmBisome) administered at a dosage of 3-5 mg/kg day. Voriconazole was administered for a median 8 (range 2-15) weeks. Response was complete and partial in two patients, respectively, stable in one, and there was no response (failure) in two. The voriconazole treatment was well tolerated. Four patients died-two of progressive aspergillosis. Three patients are alive and well 6, 5, and 4 months after the diagnosis of aspergillosis. Voriconazole appears to be an effective salvage treatment for invasive aspergillosis in pediatric patients, with good responses in patients who recover from neutropenia or are not relapsing.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Anemia, Refractory; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Bone Marrow Transplantation; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic Neoplasms; Humans; Leukemia, Myelomonocytic, Acute; Male; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Time Factors; Treatment Outcome; Triazoles; Voriconazole

A 19-year-old female with aplastic anemia who developed subglottal aspergillosis is reported. She presented with fever, cough and stridor. Inspiratory dyspnea progressed rapidly and emergent tracheostomy was performed, which confirmed the diagnosis. In spite of intensive anti-fungal treatment combined with adoptive immunotherapy, Aspergillus infection expanded and she died of pulmonary aspergillosis. Autopsy revealed the fungal mass obstructing the trachea and disseminated pulmonary aspergillosis. Difficulties in diagnosis and management of subglottal Aspergillus infection are discussed.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Fatal Outcome; Female; Fluconazole; Humans; Itraconazole; Larynx; Methylprednisolone; Opportunistic Infections

Invasion of the major airways is a rare manifestation of respiratory tract involvement by Aspergillus sp. and is seen almost exclusively in immunocompromised patients. We present calcification as a new feature of this condition and its demonstration by ultrasound in a 15-year-old boy with severe neutropenia secondary to aplastic anaemia.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Calcinosis; Humans; Immunocompromised Host; Male; Neutropenia; Trachea; Tracheal Diseases; Ultrasonography

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Brain Diseases; Drug Carriers; Humans; Immunosuppressive Agents; Liposomes; Male

A retrospective analysis of 48 patients with documented or probable invasive aspergillosis (IA) prior to bone marrow transplantation (BMT) was conducted in 16 centers. Treatment of primary IA was medical in all 48 patients and surgical in 20; clinicoradiological resolution of IA occurred in 30 of 48 patients. Pretransplantation risk factors for relapse IA, total mortality, and IA-related mortality were analyzed by multivariate logistic regression with the following dichotomous risk factors: surgery as part of the initial treatment, resolution of IA by the time of BMT, donor type, conditioning regiment, total-body irradiation, T cell depletion, immunosuppressive therapy, type of antifungal prophylaxis, and growth factor prophylaxis. Conditioning with busulfan/cyclophosphamide was associated with a beneficial outcome for total survival and reduced IA-related mortality. Posttransplantation risk factors such as the development of graft-vs.-host disease (GVHD), therapy for GVHD, and the duration of neutropenia did not have a significant effect on relapse IA, IA-related mortality, or total mortality. The overall incidence of relapse IA was lower than expected (33% [16 of 48 patients]), but the mortality rate among relapsed patients was 88% (14 of 16). Patients receiving prophylaxis with absorbable or intravenous antifungals had less relapses of IA than did those not receiving prophylaxis (12 of 41 vs. four of seven, respectively). This finding reflects the need for better prophylaxis and new antifungal treatments for patients undergoing BMT who have a history of IA.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Flucytosine; Humans; Logistic Models; Multivariate Analysis; Neoplasms; Recurrence; Regression Analysis; Retrospective Studies; Risk Factors; Transplantation Conditioning

We report the first case of invasive disease caused by Fusarium chlamydosporum. The patient had aplastic anemia with prolonged neutropenia and was treated with immunosuppressive therapy. While she was receiving empirical amphotericin B, a dark crusted lesion developed on her nasal turbinate. Histologic analysis revealed invasive hyaline hyphae and some darkly pigmented structures that resembled conidia of dematiaceous molds. Only after the mold was grown in culture were characteristic colonial morphology, phialides, conidia, and chlamydospores evident, thus permitting the identification of F. chlamydosporum. This case illustrates the ever-increasing spectrum of pathogenic Fusarium spp. in immunocompromised patients and emphasizes the potential pitfalls in histologic diagnosis, which may have important treatment implications.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Female; Fusarium; Humans; Immunocompromised Host; Mycoses; Neutropenia; Nose

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Brain Abscess; Female; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole; Liposomes; Lung Diseases, Fungal; Tomography, X-Ray Computed

Mucormycosis is an uncommon severe life-threatening fungal infection in the immunocompromised host caused by fungi belonging to the order Mucorales, most commonly Rhizopus arrhizus (R. oryzae). We report a patient who developed a severe right atrial catheter exit site infection with Absidia corymbifera. The catheter was removed and necrotic tissue debrided. With liposomal amphotericin B and G-CSF, the infection subsided. He remains well 8 months later.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Bone Marrow Transplantation; Catheterization, Central Venous; Child; Dermatomycoses; Humans; Immunocompromised Host; Male; Mucorales; Mucormycosis; Opportunistic Infections

We report the occurrence of invasive Candida albicans infection with disseminated cutaneous Candida granulomas in a patient with aplastic anaemia after viral hepatitis. Fungal elements in a skin biopsy specimen were detected by PAS stain and identified as Candida sp. by immunohistochemistry directed against the C. albicans mannan surface antigen. Based on rapid diagnosis of Candida granuloma and by Candida-positive cultures of blood and swabs, systemic treatment with liposomal amphotericin B led to survival of the patient.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibodies, Monoclonal; Antifungal Agents; Antigens, Fungal; Antigens, Surface; Candida albicans; Candidiasis; Dermatomycoses; Granuloma; Hepatitis, Viral, Human; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunohistochemistry; Male; Mannans; Polysaccharides, Bacterial; Sepsis

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: Adult; Amphotericin B; Anemia, Aplastic; Cyclosporine; Drug Interactions; Humans; Liposomes; Male; Myoclonus; Tremor

Mucor ramosissimus Samutsevitsch is presented for the first time as an etiologic agent of cutaneous zygomycosis in a patient with aplastic anemia on immunosuppressive therapy. This report also represents the third case caused by this species reported in the literature. A biopsy taken from a lesion on the patient's thigh revealed broad, nonseptate, nonbranching hyphae compatible in morphology with a Zygomycete; M. ramosissimus was cultured twice from the thigh lesion. The patient was treated successfully with amphotericin B. Identifying features of M. ramosissimus include the following: numerous sporangia lacking columellae and resembling those of Mortierella spp., short, erect sporangiophores repeatedly branching sympodially; tough, persistent, and diffluent sporangial walls; numerous oidia in chains; extremely low colonies; and restricted growth at 36 degrees C. This paper describes the isolate and strives to alert the clinical microbiologist to this rarely reported pathogen.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Dermatomycoses; Female; Humans; Mucor; Mucormycosis; Thigh

We report on a patient with aplastic anaemia and an invasive aspergillosis of the lung with subsequent osteomyelitis of the ribs. Diagnosis was made by puncture of the soft tissues and isolation of Aspergillus fumigatus. Treatment with amphotericin B induced renal function disturbances. It was successfully replaced by AmBisome. Healing occurred with recovery of the immunity of the patient. The literature on Aspergillus osteomyelitis is reviewed.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Drug Carriers; Drug Therapy, Combination; Humans; Liposomes; Male; Osteomyelitis

A preparative regimen for allogeneic bone marrow transplantation, consisting of total lymphoid irradiation (TLI) with 750 cGy and cyclophosphamide (CY), was used in five girls with aplastic anemia. All patients received bone marrow from HLA matched/mixed lymphocyte culture negative siblings. In our regimen the "inverted Y" field to irradiate the pelvic nodes was modified, which did not include the whole pelvic cavity in an attempt to protect the ovaries from irradiation. Although some of the pelvic nodes was supported not to be irradiated in order to protect the ovaries, engraftment occurred in all five patients including four who had been transfused prior to transplantation. All five are alive from 47 days to 1378 days (median 285 days) after transplantation without transplantation-associated complications. The calculated dose to the ovaries was sixteen percent of the entire dose of the regimen. Both of the two evaluable patients that had received transplantation just before or during the puberty are developing normal sex maturity including menstruation. This study suggests that our preparative regimen is effective not only for engraftment of the donor marrow but also for protecting the ovaries from irradiation.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Lymphatic Irradiation; Pelvis; Polymyxin B; Prognosis; Vancomycin

Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients. In vitro susceptibility studies demonstrated that both index strains of T. beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum. The minimum lethal concentration for both isolates was greater than or equal to 18 micrograms/ml. Five of seven other isolates were found to have a similar pattern of amphotericin B resistance. The fact that the minimum lethal concentration of T. beigelii was many times greater than its MIC was consistent with a resistance pattern of tolerance. We concluded that T. beigelii may be resistant in vitro to amphotericin B and that this in vitro resistance was correlated with refractory, disseminated trichosporonosis in granulocytopenic patients. T. beigelii should be included in the expanding list of amphotericin B-resistant fungi.

Topics: Adolescent; Aged; Agranulocytosis; Amphotericin B; Anemia, Aplastic; Drug Resistance, Microbial; Humans; Male; Microbial Sensitivity Tests; Mitosporic Fungi; Mycoses; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporon

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

A 22-yr-old man with aplastic anaemia was treated with high dose methylprednisolone. A month later he developed severe epistaxis which was not controlled by regular platelet transfusions. A balloon catheter inserted into the left nostril caused necrosis of the left ala nasi accompanied by gross facial oedema. He received treatment with horse ALG for aplastic anaemia but developed gross facial oedema and anaesthesia of incisor and canine teeth on the right side. Radiographs initially showed thickening of the maxillary antral mucosa and later erosion of the maxilla over the anaesthetic region. A biopsy specimen of this region contained hyphae of zygomycetes. He was treated with amphotericin B and a second course of antilymphocyte globulin followed by oxymetholone. He has made a satisfactory clinical and haematological recovery.

Topics: Adult; Amphotericin B; Anemia, Aplastic; Antilymphocyte Serum; Humans; Male; Mycoses

We describe a case of akinetic mutism associated with diffuse cerebral leukoencephalopathy, which developed in a bone marrow transplant recipient following total-body irradiation and amphotericin B chemoprophylaxis. A trial of high-dose bromocriptine did not stimulate purposeful verbal or motor activity. Fluorine 18-fluorodeoxyglucose/positron emission tomographic studies, performed before and during bromocriptine therapy, demonstrated cerebral hypometabolism and treatment-related decreases in regional cerebral blood volume. We conclude that whole-brain or total-body irradiation may increase blood-brain barrier permeability to polyene antibiotics, and that high-dose therapy with dopamine agonists is unlikely to benefit patients with akinetic mutism due to diffuse white-matter lesions.

Topics: Adult; Akinetic Mutism; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Bromocriptine; Cerebrovascular Circulation; Deoxyglucose; Fluorodeoxyglucose F18; Glucose; Humans; Male; Tomography, Emission-Computed; Whole-Body Irradiation

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

Topics: Amphotericin B; Anemia, Aplastic; Aspergillosis; Candida; Candidiasis; Drug Resistance, Microbial; Female; Humans; Lung Diseases, Fungal; Middle Aged; Time Factors

Three young patients with severe aplastic anemia undergoing intensive immunosuppressive therapy developed fever and pulmonary infiltrates during longlasting severe granulocytopenia, despite multiple broad spectrum antibiotic combinations and granulocyte transfusions. Invasive pulmonary aspergillosis was diagnosed only by thoracotomy. In conjunction with high dose amphotericin-B therapy complete resolution of aspergillosis was achieved in two cases, paralleled by slow recovery of bone marrow function, whereas in the third case only a partial remission was possible together with transient amelioration of granulopoiesis. We suggest early aggressive surgical methods to establish the diagnosis of aspergillosis in these severely menaced patients, so that antifungal therapy with high dose amphotericin-B can be initiated at an early stage.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Aspergillosis; Child; Humans; Lung Diseases, Fungal; Male; Thoracic Surgery

The development of resistance to amphotericin B and nystatin in yeast isolates was determined. Organisms recovered from patients on the oncology service, undergoing extensive chemotherapy for acute leukemia and bone marrow transplantation, were compared with yeasts recovered from patients on other services in the same hospital over a 7-month period. An agar dilution method was used to assay the susceptibility for each antibiotic; resistance was defined as a minimal inhibitory concentration of greater than or equal to 2 micrograms/ml for amphotericin B and greater than or equal to 16 micrograms/ml for nystatin. None of 625 isolates from 238 patients on non-oncology services demonstrated polyene resistance. Resistance only occurred in a subpopulation of oncology patients, in which 55 isolates (7.4%) from six patients (8.6%) exhibited polyene resistance. Resistance yeasts included Candida albicans (three strains), Candida tropicalis (one strain), and Torulopsis glabrata (two strains). All of the patients from whom resistant yeasts were recovered had experienced extensive chemotherapy with cytotoxic agents, granulocytopenia, and long-term treatment with both antibacterial and polyene antibiotics. Resistance to 2 micrograms of amphotericin B per ml and to 16 micrograms of nystatin per ml was associated with loss or marked depression of ergosterol in the cell membrane as measured by ultraviolet spectra. A significant incidence of polyene resistance in an oncology subpopulation was documented, suggesting a need for susceptibility testing in patients who are at high risk for development of drug-resistant fungal pathogens.

Topics: Amphotericin B; Anemia, Aplastic; Anti-Bacterial Agents; Drug Resistance, Microbial; Ergosterol; Humans; Leukemia; Mycoses; Polyenes; Yeasts

Topics: Agranulocytosis; Amphotericin B; Anemia, Aplastic; Anemia, Hemolytic; Anti-Bacterial Agents; Ataxia; Bacitracin; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Chloramphenicol; Deafness; Gastrointestinal Diseases; Gentamicins; Humans; Kanamycin; Kidney Diseases; Leukopenia; Lung Diseases; Neomycin; Neuromuscular Diseases; Nitrofurantoin; Optic Neuritis; Peripheral Nervous System Diseases; Skin Diseases; Streptomycin; Sulfonamides; Tetracycline; Thrombocytopenia; Vertigo

Topics: Adult; Amphotericin B; Anemia, Aplastic; Blood; Candida; Candidiasis; Catheterization; Cryptococcus; Female; Fungi; Humans; Immunity; Immunosuppressive Agents; Leukopenia; Male; Middle Aged; Mycoses; Neoplasms; Prognosis

Topics: Amphotericin B; Anemia; Anemia, Aplastic; Bone Marrow Examination; Diagnosis, Differential; Histoplasmosis; Humans; Leukemia; Pancytopenia; Prednisolone

Topics: Amphotericin B; Anemia; Anemia, Aplastic; Blood; Blood Transfusion; Erythrocytes; Hematocrit; Hemolysis; Humans; Iron; Nitrogen; Toxicology; Uremia