amphotericin-b and Opportunistic-Infections

Mucormycosis is an aggressive, rare and opportunistic infectious disease, with a high mortality rate. Etiologic agents are filamentous fungi, and infection among humans normally occurs through spore inhalation. A 61-year-old male individual, presenting left eye amaurosis, dark epistaxis, hyperalgesia and malodor underwent clinical examination, which detected ulcerative lesion and wide bone exposure in the hard palate and alveolar ridge. Direct microbiological examination, microbiological culture and lesion biopsy were performed. Non-septate smooth fungal hyphae forming right angles with each other were observed through the direct microbiological examination. Microbiological culture revealed fast-growing fungal colonies with cottony texture, identified as Rhizopus sp. Histopathological examination exhibited necrosis areas, intense mononuclear inflammatory infiltrate and bulky hyphae, thus concluding the mucormycosis diagnosis. Amphotericin B antifungal therapy and surgical intervention were adopted as treatment. The patient was then rehabilitated with maxillofacial prosthesis, subsequently to the healing of the surgical wound.

Topics: Amphotericin B; Antifungal Agents; Humans; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Rhizopus

Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.. A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.. This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cellulitis; Coinfection; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Male; Mycobacterium haemophilum; Mycobacterium Infections; Nitriles; Opportunistic Infections; Primary Myelofibrosis; Pyrazoles; Pyrimidines

Geotrichum capitatum is a rare fungal pathogen that has infrequently affected immunocompromised patients with onco-hematologic diseases. Geotrichum capitatum invasive infection has been associated with poor prognosis, with a mortality rate ranging from 50% to 90%. Here, we report the first case of Geotrichum capitatum invasive fungal infection in a liver transplant recipient from an unrelated deceased donor, who was effectively treated with amphotericin B and voriconazole. We also reviewed the available literature in the field.

Topics: Amphotericin B; Antifungal Agents; Fatal Outcome; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Fungal Infections; Liver Transplantation; Male; Middle Aged; Multiple Organ Failure; Opportunistic Infections; Saccharomycetales; Sepsis; Treatment Outcome; Voriconazole

Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature.. Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole.. Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.

Topics: Adult; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Humans; Itraconazole; Kidney Transplantation; Male; Meningitis, Fungal; Middle Aged; Opportunistic Infections; Skin Ulcer; Sporotrichosis; Transplant Recipients

Cryptococcus albidus, synonymous with Naganishia albida, rarely causes opportunistic infection in immunocompromised individuals. Its clinical features, particularly in children, are not well defined. Here, we report a case of C albidus fungemia in an immunosuppressed child; we also present results of a systematic review, for which we searched PubMed, Embase, and Web of Science using the keywords "cryptococcus" and "albidus." Our goal was to describe the spectrum of disease, diagnostic approaches, therapies, and outcomes. We identified 20 cases of invasive infection, only 2 of which involved children, and 7 cases of noninvasive infection. The reports originated in the Americas, Europe, and Asia. Of those with invasive infection, 16 (80%) patients had an underlying chronic disorder or had received immunosuppressive therapy, 8 (40%) had fungemia, and 6 (30%) had a central nervous system infection. The attributable case fatality rate was 40%. C albidus is an opportunistic yeast that can rarely cause life-threatening fungemia and central nervous system infection in individuals of any age, especially those who are immunocompromised.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Cryptococcus; Female; Fluconazole; Humans; Immunocompromised Host; Infant, Newborn; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Takayasu Arteritis; Transplantation, Autologous

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

Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis.. We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient's treatment, but unfortunately, he died three days later. Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy.. Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amphotericin B; Antifungal Agents; Antigens, Fungal; China; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Humans; Male; Meningitis; Middle Aged; Opportunistic Infections; Treatment Outcome

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

Primary cutaneous aspergillosis is a rare, life-threatening fungal infection in premature infants. We report a case of primary cutaneous aspergillosis caused by Aspergillus tamarii in an extremely low birthweight infant. The infant was delivered by cesarean section with complications from an intrauterine infection, brain intraventricular hemorrhage, tension pneumothorax and cardiac tamponade. On the 12th day of life, he developed erythematous maceration with erosion on his back. Septate hyphae were detected on two occasions from specimens of the skin lesion. The manifestations of the colony and slide culture showed the characteristics of A. tamarii. The nucleotide sequences of internal transcribed spacer regions of the ribosomal RNA gene, partial sequences of β-tubulin and calmodulin gene were compatible with those of A. tamarii. Of the known Aspergillus species, Aspergillus fumigatus and Aspergillus flavus have been reported in previous studies as the major causative agents in primary cutaneous aspergillosis, whereas human infection by A. tamarii is rare. We consider that A. tamarii is important as an unusual opportunistic human pathogen among premature infants.

Topics: Administration, Cutaneous; Administration, Intravenous; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Cesarean Section; Clotrimazole; Dermatomycoses; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Ointments; Opportunistic Infections; Skin; Treatment Outcome

Visceral leishmaniasis has been recognized as an opportunistic infection affecting people with cellular-immunity impairment, including hematopoietic cell transplantation (HCT) recipients. We describe the case of a young Italian man with Hodgkin lymphoma, who developed visceral leishmaniasis after multiple lines of chemotherapy and allogenic HCT. Literature review of visceral leishmaniasis in HCT recipients was also performed. Eleven patients (median age 50 years, 9 male) developed visceral leishmaniasis after allogenic (n = 9) and autologous (n = 2) HCT. Most of them presented with fever and pancytopenia. Bone marrow examination was the main diagnostic technique; liposomal amphotericin B was the treatment of choice. Four out of eight patients (for whom data are available) experienced visceral leishmaniasis relapse. Visceral leishmaniasis in HCT recipients is a rare event that should be suspected in patients with persistent fever, pancytopenia and possible exposure to Leishmania spp., remembering that - as well as South-East Asia, East Africa and South America - it is endemic in several European regions.

Topics: Adult; Amphotericin B; Antibodies, Protozoan; Antineoplastic Agents; Antiprotozoal Agents; Bone Marrow Examination; Fatal Outcome; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leishmania; Leishmaniasis, Visceral; Male; Middle Aged; Opportunistic Infections; Recurrence

Mucormycosis is a rare fungal infection caused by Mucor indicus. Phylogenetic analysis of many M. indicus isolates, mainly sampled from different clinical and environmental specimens collected worldwide, revealed two genotypes, I and II, based on ITS and D1/D2 LSU rDNA sequences. A retrospective review of the literature revealed 13 cases. Eight (76.9%) patients had disseminated infections, and the overall mortality rate was 30.7%. A pulmonary infection caused by M. indicus genotype I in a liver transplant recipient was disseminated to include the skin and was successfully treated with liposomal amphotericin B and aggressive surgery. M. indicus can infect a wide variety of patients with no real preference for the site of infection. We concluded that M. indicus has emerged as a significant cause of invasive mycosis in severely immunocompromised patients worldwide. Early diagnosis and initiation of appropriate therapy could enhance survival in these immunocompromised patient populations.

Topics: Aged; Amphotericin B; Antifungal Agents; Communicable Diseases, Emerging; DNA, Ribosomal Spacer; Genotype; Humans; Immunocompromised Host; Invasive Fungal Infections; Liver Transplantation; Lung; Male; Middle Aged; Mucor; Mucormycosis; Opportunistic Infections; Phylogeny; Retrospective Studies; Skin

Histoplasmosis is an endemic fungus in several regions of the United States. The diagnosis and treatment of this infection can be challenging in pediatric oncology patients. We present 5 patients diagnosed with histoplasmosis while receiving treatment at a midsize pediatric oncology center in Iowa. Two cases occurred in patients with acute lymphoblastic leukemia and 3 cases in patients with solid tumors. All patients were treated with antifungal therapy and demonstrated excellent clinical response. Histoplasmosis should be considered as a potential cause of nonspecific febrile illness, pulmonary masses, and bone marrow suppression in immunocompromised patients in endemic regions. Prompt and accurate diagnosis can facilitate timely antifungal therapy and avoidance of prolonged hospital stays, invasive testing, unnecessary antibiotics, and unwarranted anticancer therapies.

Topics: Abdominal Neoplasms; Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Burkitt Lymphoma; Child; Child, Preschool; Combined Modality Therapy; Desmoplastic Small Round Cell Tumor; Diagnosis, Differential; Early Diagnosis; Endemic Diseases; Febrile Neutropenia; Histoplasmosis; Humans; Immunocompromised Host; Infant; Iowa; Itraconazole; Lung; Lung Neoplasms; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cryptococcus; Cytarabine; Dermatomycoses; Echinocandins; Exanthema; Fever; Fungemia; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipopeptides; Male; Micafungin; Opportunistic Infections; Retrospective Studies; Saccharomyces; Salvage Therapy; Trichosporon; Ustilaginales; Vidarabine; Voriconazole; Yeasts

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Hematologic Neoplasms; Humans; Lymphoma; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections

Mucormycosis is an opportunistic mold infection whose management is difficult, as there is a paucity of evidence-based data. We summarize the latest advances in diagnosis and management of mucormycosis in transplant recipients.. There is promise for improvement in nonculture-based diagnostics with new biomarkers of Mucorales DNA that can be used for early diagnosis, and monitoring of response. Antifungal treatment consists of high-dose lipid formulations of amphotericin B or isavuconazole as the first-line therapy and posaconazole as salvage therapy. The new, pharmacokinetically more reliable formulations of posaconazole (intravenous, extended-release tablets) are welcomed improvements. Yet, the role of combination therapy is still uncertain. Surgery had a significant role in selected cases, such as in patients with rhinosinusitis form of mucormycosis, which nowadays can be performed with minimal invasive technique.. Mucormycosis remain a life-threatening opportunistic mold infection among transplant patients. Early diagnosis, prompt treatment with effective antifungals in combination with surgery if feasible is essential. Immune adjunct therapy and improvement of early diagnostics are important areas for future research. There are good prospects of progress in diagnostics and management of mucormycosis in transplant patients.

Topics: Amphotericin B; Antifungal Agents; DNA, Fungal; Humans; Mucorales; Mucormycosis; Nitriles; Opportunistic Infections; Pyridines; Salvage Therapy; Transplant Recipients; Triazoles

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

Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Biomarkers; Echinocandins; Hematologic Neoplasms; Humans; Neutropenia; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Tomography, X-Ray Computed; Voriconazole

Penicilliosis is an opportunistic infection in HIV-infected and other immunocompromised patients mostly in Southeast Asia, Southern China, Hong Kong, and Taiwan, with respiratory manifestations in about one-third of patients. We report the case of a 26-year-old non-HIV immunocompromised patient presenting with an airway obstruction caused by penicilliosis, together with a review of the literature of this rare condition.

Topics: Adult; Airway Obstruction; Amphotericin B; Bronchoscopy; Humans; Immunocompromised Host; Itraconazole; Lung Diseases, Fungal; Lupus Erythematosus, Systemic; Male; Mycobacterium Infections, Nontuberculous; Opportunistic Infections; Penicillium

A 28-year-old man presented at our clinic with 1-month history of an ulcer covered with crust on his left anterior tibia. Based on the morphological features and molecular identification, the patient was diagnosed as cutaneous alternariosis caused by Alternaria arborescens. He was successfully cured by oral itraconazole and topical use of 0.25% liposomal amphotericin B. A review of published studies revealed 29 cases of cutaneous alternariosis. Most cases (90%) occurred in immunosuppressed patients; itraconazole (59%) and voriconazole (24%) are the most effective treatments of choices.

Topics: Adolescent; Adult; Aged; Alternaria; Alternariosis; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Humans; Itraconazole; Male; Middle Aged; Opportunistic Infections; Skin; Treatment Outcome

Candida infection is a relatively common hematogenous nosocomial infection in immunocompromised patients. However, renal disease remains unusual. The mode of presentation in the case reported herein was lumbar pain with fever and hydronephrosis of the left kidney due to a fungal bezoar in the renal pelvis. Clinical and biological suspicion of this disease must quickly lead to ultrasound examination to confirm the diagnosis.

Topics: Amphotericin B; Antifungal Agents; Bezoars; Candidiasis; Child; Diabetes Mellitus, Type 1; Diagnosis, Differential; Female; Flank Pain; Humans; Kidney Pelvis; Opportunistic Infections; Ultrasonography

Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.. To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.. Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.. Randomised clinical trials comparing voriconazole with amphotericin B or fluconazole.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.. Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.. Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although its effect seems to be equivocal.. To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency.. We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.. Randomised clinical trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B.. Data on mortality, invasive fungal infection and colonisation were independently extracted by both authors. A random-effects model was used unless the P value was greater than 0.10 for the test of heterogeneity.. We included 14 trials (1569 patients). The drugs were given prophylactically in 12 trials and as treatment in two. Eleven trials were in acute leukaemia, solid cancer, or bone marrow recipients; one in liver transplant patients; one in critically ill surgical and trauma patients; and one in AIDS patients. Nystatin was compared with placebo in three trials, with fluconazole in 10, and amphotericin B in one; the dose varied from 0.8 MIE to 72 MIE daily and was 2 mg/kg/d in a liposomal formulation. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk (RR) 0.85, 95% confidence interval (CI) 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (RR 0.75, 95% CI 0.54 to 1.03) whereas fluconazole was more effective in preventing invasive fungal infection (RR 0.40, 95% CI 0.17 to 0.93) and colonisation (RR 0.50, 95% CI 0.36 to 0.68). There were no proven fungal infections in a small trial that compared amphotericin B with liposomal nystatin. The results were very similar if the three studies that were not performed in cancer patients were excluded. For the 2011 and 2014 updates no additional trials were identified for inclusion.. Nystatin cannot be recommended for prophylaxis or the treatment of Candida infections in immunodepressed patients.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candidiasis; Fluconazole; Humans; Immunocompromised Host; Liposomes; Mycoses; Nystatin; Opportunistic Infections; Randomized Controlled Trials as Topic

Protothecosis is an opportunistic infection caused by Prototheca, usually called as saprophytes, and is frequently found in natural and living surroundings with low virulence, but may cause chronic infection in immunocompromised individuals. We report a case of cutaneous protothecosis with zopfii var. portoricensis infection in a 66-year-old diabetic woman following hand surgery on middle right finger. Mycology study showed that smooth, creamy white, yeast-like colonies grown after necrotic tissue was cultured on Sabouraud dextrose agar at both 37 and 25°C. The organism was then identified as Prototheca zopfii var. portoricensis by molecular identification and also found from histopathology of the lesion. The lesion got improved with intravenous amphotericin B and itraconazole.

Topics: Aged; Amphotericin B; Diabetes Mellitus; Female; Humans; Itraconazole; Opportunistic Infections; Postoperative Complications; Prototheca; Skin Diseases

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

Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Considerable progress in treating IFDs has been achieved over the last years, through the availability of new, effective drugs. However, many of these newer antifungal agents have some limitations, such as their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions.. This article reviews the literature evaluating the safety profile of the lipid formulations of Amphotericin B, echinocandins, and second-generation triazoles. It also discusses the possible drug-drug interactions with some drugs commonly used in allogeneic HSCT.. Nephrotoxicity is the most frequent side effect of lipid formulations of Amphotericin B, which may cause a reduced clearance of the renally eliminated calcineurin inhibitors used for the control of Graft Versus Host Disease. Second-generation triazoles are characterized by a limited toxicity profile, but also by frequent drug-drug interactions with other drugs metabolized by the hepatic enzymes. The echinocandins are characterized by a very low toxicity profile and negligible interactions with other drugs. Such pharmacological knowledge is crucial in the daily care of allogeneic HSCT patients.

Topics: Amphotericin B; Animals; Antifungal Agents; Drug Interactions; Echinocandins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Mycoses; Opportunistic Infections; Pharmacovigilance; Renal Insufficiency; Stem Cell Transplantation; Triazoles

Penicillium marneffei is an important opportunistic pathogen in Southeast Asia in HIV-positive individuals, but it rarely infects non-HIV ones. Four SLE patients with disseminated penicilliosis had been previously reported out of which 3 died. We describe a 46-year-old Chinese woman who had a 10 years history of SLE, associated with disseminated Penicillium marneffei infection, which presented as fever, subcutaneous masses, and fine nodular shadows disseminated over lung fields. She was initially misdiagnosed as miliary tuberculosis and panniculitis that did not respond to anti-tubercular drugs and prednisone. The correct diagnosis was finally made by histopathology and tissue culture and also culture from exudate. She responded well to antifungal therapy in the form of intravenous amphotericin B for 2 weeks followed by itraconazole plus fluconazole. The cutaneous lesions were cured leaving behind scars by secondary suture after times of epluchage, and the fine nodular shadows over lungs disappeared finally. She had no recurrence on 8 months of follow-up. We also review the literature on this topic.

Topics: Amphotericin B; Antifungal Agents; China; Dermatomycoses; Female; Fluconazole; Humans; Itraconazole; Lupus Erythematosus, Systemic; Middle Aged; Mycoses; Opportunistic Infections; Penicillium

Rhodotorula is emerging as an important cause of nosocomial and opportunistic infections. We present two cases of Rhodotorula mucilaginosa fungemia diagnosed over a period of 3 months at our hospital. The first case was of a pre-term neonate in the neonatal ICU who presented with respiratory failure and sepsis. The second involved an adult female who had been injured in a road traffic accident requiring an operation for a hematoma and was later shifted to the medical ICU. For a new hospital like ours, finding two cases of Rhodotorula fungemia within a span of 3 months prompted us to describe them in this report. These cases emphasize the emerging importance of Rhodotorula mucilaginosa as a pathogen and the importance of identification and MIC testing for all fungal isolates recovered from the blood stream.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Microbial Sensitivity Tests; Middle Aged; Opportunistic Infections; Pyrimidines; Rhodotorula; Treatment Outcome; Triazoles; Voriconazole; Wounds and Injuries

Aspergillosis remains a significant cause of morbidity and mortality. The spectrum of disease is diverse and ranges from noninvasive disease with an excessive immune response, such as in allergic bronchopulmonary aspergillosis (ABPA), to a lack of an immune response as seen in patients with quantitative or qualitative granulocyte deficits and subsequent invasive pulmonary aspergillosis. Noninvasive diagnostic testing has improved the time to initiation of effective antifungal therapy, and numerous agents in different therapeutic classes are now available as treatment options. Voriconazole remains the preferred agent in the treatment of invasive pulmonary aspergillosis, and recent data have increased interest in the potential of combination therapy against this often lethal infection. The role of host genetics in selecting patients that may benefit from more aggressive antifungal prophylaxis or treatment practices remains unclear but is likely to guide therapeutic choices as newer data become available.

Topics: Amphotericin B; Antifungal Agents; Aspergillus; Disease Susceptibility; Drug Resistance, Fungal; Echinocandins; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Opportunistic Infections; Pulmonary Aspergillosis; Triazoles

The study includes a case report and a literature review. The main objective of this study is to present a case of spondylodiscitis due to a fungal pathogen, Blastoschizomyces capitatus and to review the published literature on this emergent fungus in etiology of spondylodiscitis, and osteomyelitis. Osteoarticular involvement due to B. capitatus has been reported in six cases, and vertebral involvement has been seen in five of them. All of these cases had underlying malignancy. Infection is usually advanced at presentation. Case notes and online databases were reviewed. Organism was isolated from bone material in all of the cases and antibiotic treatment by antifungal agents cured the infection. We present another case of infectious spondylodiscitis due to B. capitaus, which is reported first in Turkey and tried to attract attendance to this emergent fungal pathogen as an etiologic agent of spine infections in cancer patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Dipodascus; Discitis; Fluconazole; Humans; Itraconazole; Ketoconazole; Lumbar Vertebrae; Male; Microbial Sensitivity Tests; Naphthalenes; Opportunistic Infections; Radiography; Terbinafine; Treatment Outcome

Rhino-orbito-cerebral mucormycosis (ROCM) is a rare, fulminant opportunistic fungal infection that is mostly seen in immunocompromised or diabetic patients. The disease should be recognised and treated immediately. We present here MR imaging findings of two patients with histopathologically proven ROCM. One of the cases had a history of corticosteroid treatment and iatrogenic diabetes mellitus and although amphotericin B was started immediately, the disease progressed and surgical debridement was necessary. The second case was a patient with diabetes mellitus type 1 in whom ROCM had occurred following an abdominal surgery; amphotericin B treatment alone was adequate in this patient.

Topics: Adrenal Cortex Hormones; Amphotericin B; Antifungal Agents; Brain Diseases; Diabetes Complications; Diabetes Mellitus, Type 1; Humans; Iatrogenic Disease; Immunocompromised Host; Male; Middle Aged; Mucormycosis; Nose Diseases; Opportunistic Infections; Orbital Diseases; Purpura, Thrombocytopenic, Idiopathic

Cunninghamella bertholletiae infection occurs most frequently in neutropenic patients affected by haematological malignancies, is associated with an unfavourable outcome. We report a case of rhino-mastoidal fungal infection in a leukaemic patient. Bioptical tissue cultures yield the isolation of a mould with typical properties of Cunninghamella species. Liposomal amphotericin B (L-Amb) therapy combined with surgical intervention brought the lesion to recovery. Nevertheless, the patient died 14 days after bone marrow transplantation (BMT) from bacterial sepsis. Mastoiditis was documented at CT-scan. The conditioning regimen probably caused the reactivation of the Cunninghamella infection that led to the patient's fatal outcome; fungal hyphae were detected after autopsy of brain and lung tissue.

Topics: Amphotericin B; Bone Marrow Transplantation; Cunninghamella; Humans; Immunocompromised Host; Leukemia, Myeloid; Mucormycosis; Opportunistic Infections

Invasive fungal infections (IFI) are the main cause of infectious death in cancer patients, especially in hematological malignancies and hematopoietic transplant recipients. Current epidemiology is characterized by a predominance of IFI caused by molds, mainly aspergillosis, along with a emergence of hard-to-treat fungi such are Zygomicetes, Fusarium and Scedosporium. Voriconazole is a broad spectrum antifungal agent with oral and intravenous formulations, approved by the EMEA for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, IFI caused by fluconazole-resistant species of Candida as well as Scedosporium and Fusarium infections. However, its use in clinical practice is broader, as empirical antifungal treatment and as secondary prophylaxis. It should be kept in mind the possibility of breakthrough IFI, particularly zygomycosis, in patients treated with voriconazole for long periods.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Drug Resistance, Fungal; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Multicenter Studies as Topic; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Salvage Therapy; Spain; Triazoles; Voriconazole; Zygomycosis

Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy are used both empirically and therapeutically in these patients.. To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.. MEDLINE and the Cochrane Library (May 2005). Letters, abstracts and unpublished trials were accepted. Contact to authors and industry.. Randomised trials comparing voriconazole with amphotericin B or fluconazole.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by two authors independently.. Two trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infections) in neutropenic cancer patients (849 patients, 58 deaths). The other trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from analysis by the authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication and substitution with electrolytes and salt water to avoid handicapping this drug. This choice of comparator resulted in a marked difference in the duration of treatment on trial drugs (77 days with voriconazole versus 10 days with amphotericin B), and precludes meaningful comparisons of the benefits and harms of the two drugs.. Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

An unusual central venous catheter (CVC)-related infection caused by Candida membranaefaciens in a patient with non-Hodgkin's lymphoma is described. Clinical signs and microbiological results observed in this case may support the hypothesis of an emerging CVC-related fungaemia, because of new azole-resistant yeast, successfully treated with liposomal amphotericin B. To date C. membranaefaciens (the teleomorph of Pichia membranaefaciens) has traditionally been considered non-pathogenic and this report seems to be the first case of systemic fungal infection. We believe that another fungus can be added to the list of opportunistic strains.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Drug Resistance, Fungal; Hodgkin Disease; Humans; Opportunistic Infections; Prosthesis-Related Infections

Persistent or recurrent unexplained fever in neutropenic patients receiving antibiotics can be caused by invasive fungal infections, which are often difficult to diagnose. Early trials of empirical antifungal therapy with amphotericin B deoxycholate (AmB) documented reductions in the frequency of and the morbidity and mortality associated with invasive fungal infections. Because of AmB's infusional and renal toxicities, subsequent trials used newer, less toxic agents, such as the lipid formulations of AmB, the extended-spectrum azoles, and, more recently, the echinocandins. To date, alternatives to AmB have shown less toxicity, but improved efficacy has been less clear. Overall, empirical antifungal therapy can help prevent the morbidity associated with many fungal infections, eliminate concerns about diagnostic pitfalls, and prevent breakthrough undetected infections. However, its potential shortcomings are overtreatment, toxicity, and increased treatment-related costs when treatment is given to persons not needing it. Newer diagnostic tools are needed to target those most in need of antifungal therapy.

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Deoxycholic Acid; Drug Combinations; Fever; Fluconazole; Fungemia; Humans; Immunocompromised Host; Neutropenia; Opportunistic Infections

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy; Drug Therapy, Combination; Humans; Opportunistic Infections

Zygomycosis is an opportunistic fungal infection that is increasingly reported in hematological patients. We describe 2 cases of successfully treated rhino-cerebral zygomycosis and give an overview of 120 patients from the literature with underlying hematological or oncological disorders. These data document the improved survival in sinus (15/17 patients surviving) and cutaneous (6/9 patients surviving) disease. Hematological patients with pulmonary (9/30 patients surviving) or disseminated (4/38 patients surviving) zygomycosis still have a poor prognosis. The clinical course of sinus-orbital involvement (4/11 patients surviving) follows sinus-cerebral (2/3 patients surviving) or cerebral (3/6 patients surviving) disease. Besides deoxycholate amphotericin B (AmB) (24/62 patients surviving), patients seem to benefit from liposomal amphotericin B (L-AmB) (10/16 patients surviving) or sequential AmB/L-AmB treatment (6/8 patients surviving). Alternative treatment options lead only in a few patients to success.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus fumigatus; Combined Modality Therapy; Deoxycholic Acid; Ethmoid Sinusitis; Female; Hematologic Diseases; Humans; Immunocompromised Host; Itraconazole; Ketoconazole; Liposomes; Lymphoma, Large B-Cell, Diffuse; Male; Maxillary Sinusitis; Middle Aged; Mucor; Mucormycosis; Multiple Myeloma; Nose Diseases; Opportunistic Infections; Prognosis; Treatment Outcome; Zygomycosis

Systemic infection with Aspergillus fumigatus is an opportunistic disease that affects mainly immunocompromised hosts and is associated with a high mortality rate. We report a case of A. fumigatus endocarditis after an episode of thrombotic thrombocytopenic purpura. Diagnosis was established after sudden rupture of posterior papillary muscle of the normal native mitral valve. Soon after mitral valve replacement, Aspergillus endocarditis recurred, associated with multiple peripheral emboli, which necessitated a second operation.

Topics: Amphotericin B; Anti-Infective Agents; Aspergillosis; Aspergillus fumigatus; Candidiasis; Drug Resistance, Fungal; Embolism; Endocarditis; Fatal Outcome; Female; Heart Valve Prosthesis Implantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Itraconazole; Lung Diseases, Fungal; Middle Aged; Mitral Valve Insufficiency; Opportunistic Infections; Papillary Muscles; Postoperative Complications; Prednisolone; Pseudomonas Infections; Purpura, Thrombotic Thrombocytopenic; Recurrence; Rupture, Spontaneous; Shock, Septic; Sputum; Ultrasonography; Urinary Tract Infections

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: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Azoles; Caspofungin; Drug Design; Drug Resistance, Fungal; Echinocandins; Fluconazole; Fluorouracil; Fungi; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Opportunistic Infections; Peptides; Peptides, Cyclic; Polyenes; Pyrimidines

Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal.. To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency.. MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001. Contacted industry and scanned reference lists.. Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B.. Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently. A random effects model was used unless p>0.10 for the test of heterogeneity.. We included 12 trials (1,464 patients). The drugs were given prophylactically in ten trials and as treatment in two. Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients. Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The results were very similar if the three studies which were not performed in cancer patients were excluded.. Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Fluconazole; Humans; Immunocompromised Host; Mycoses; Nystatin; Opportunistic Infections; Randomized Controlled Trials as Topic

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Flucytosine; Humans; Mitosporic Fungi; Mycoses; Opportunistic Infections

Reported here are two cases of candidemia caused by Candida lusitaniae that occurred in two immunocompromised patients at Hospital Universitario "La Fe" in Valencia, Spain. Case 1 involved a low-birth-weight premature infant with congenital nephrotic syndrome who was successfully treated with amphotericin B, and case 2 involved a 50-year old woman with a high-grade malignancy lymphoma who succumbed to the infection. Antifungal susceptibility testing of the Candida lusitaniae isolates recovered from both patients revealed sensitivity to amphotericin, 5-flucytosine and fluconazole. Results are presented and discussed together with a comprehensive review of the literature, covering all previously reported cases of fungemia caused by this emerging pathogen.

Topics: Amphotericin B; Antifungal Agents; Candida; Female; Fungemia; Humans; Infant, Newborn; Middle Aged; Opportunistic Infections

Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal.. To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency.. MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001. Contacted industry and scanned reference lists.. Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B.. Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently. The outcomes were weighted by the inverse variance. A random effects model was used unless p>0.10 for the test of heterogeneity.. We included 12 trials (1,464 patients). The drugs were given prophylactically in ten trials and as treatment in two. Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients. Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The results were very similar if the three studies which were not performed in cancer patients were excluded.. Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Fluconazole; Humans; Immunocompromised Host; Mycoses; Nystatin; Opportunistic Infections

Systemic fungal infections are an increasing problem in older adults. For several of the endemic mycoses, this increase is the result of increased travel and leisure activities in areas endemic for these fungi. Immunosuppressive agents, care in an intensive care unit, and invasive devices all contribute to infection with opportunistic fungi. Treatment of systemic fungal infections is usually with an azole or amphotericin B. The preferred regimen depends on the specific fungal infection, the site and the severity of the infection, the state of immunosuppression of the patient and the possible toxicities of each drug for a specific patient. In older adults, drug-drug interactions between the azoles and drugs commonly prescribed for older persons may lead to serious toxicity, and absorption of itraconazole can be problematic. Amphotericin B is associated with significant nephrotoxicity, especially in older adults with pre-existing renal disease, and infusion-related adverse effects. Newer lipid formulations of amphotericin B can obviate some of these toxicities, but their role in the treatment of systemic fungal infections in older adults has not yet been clarified.

Topics: Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Azoles; Dermatomycoses; Drug Interactions; Humans; Immunocompromised Host; Mycoses; Opportunistic Infections

Invasive fungal infections are rare but life-threatening infections, most often occurring in immunocompromised patients. For a long time, Amphotericin B has been the best choice for treatment, because it is fungicidal with a broad antifungal spectrum and minimal risk of resistance development. The therapeutic use of amphotericin B has, however, been limited by its toxicity-both acute as well as chronic. To counter this, amphotericin B has been encapsulated in liposomes, which reduces its toxicity and allows higher doses to be given. Ambisome is a true, spherical, small unilamellar liposome with a median size of 80 nm. The pharmacokinetic profile was changed, and the maximum concentration and AUC of amphotericin B after AmBisome treatment were greater than those found with the conventional drug. The highest tissue concentrations of AmBisome were found in the liver and spleen, and less than 1% of the administered dose was recovered in other organs. At Huddinge University Hospital, we were the first to use and report on the experience of AmBisome. We now have more than 12 years' experience in transplant recipients, with a good safety profile, improved rate of curing mycological proven infections and reduced mortality in fungal infections. In two placebo-controlled prophylactic trials, we found that AmBisome was effective for preventing fungal colonization and invasive fungal infections, respectively, in allogeneic stem cell and liver transplantation. In uncontrolled and, more recently, in randomized controlled studies at other centers, AmBisome has revealed less toxicity and an efficacy equal or superior to that of the conventional drug in treating neutropenia-associated fever and proven invasive fungal infections in both adults as well as in children. Although investigators tend to increase the dose used, the optimal dose for probable or proven infection is still under debate. Based on our own experience in using AmBisome and the experience at other centers, we can conclude that AmBisome represents a major breakthrough in the treatment of invasive fungal infections, especially in immunocompromised patients.

Topics: Amphotericin B; Antifungal Agents; Area Under Curve; Child; Female; Humans; Immunocompromised Host; Infant, Newborn; Leishmaniasis, Visceral; Liposomes; Male; Mycoses; Opportunistic Infections; Tissue Distribution; Transplantation

Efforts at preventing and treating fungal infection in hematopoietic stem cell transplant (HSCT) recipients must take into account the types of infections likely to be encountered during the different risk periods in hosts with different underlying risks. Given the emergence of molds as prevalent pathogens and the long duration of risk in allogeneic HSCT recipients, optimal antifungal prophylaxis would consist of treatment that can be given over a prolonged period and that would provide both anti-Candida and anti-Aspergillus activity. Optimal empiric therapy would consist of a broad-spectrum agent in the absence of more sensitive and specific methods for microbial diagnosis. Fluconazole (Diflucan) is currently the standard prophylactic agent for candidiasis, although mold-active agents and alternative strategies for polyene administration are being investigated. The gold standardfor empiric therapy is currently a polyene antifungal, yet an increased appreciation for amphotericin B-resistant yeasts and molds, and less toxic mold-active alternatives, might lead to the use of other compounds in the future. The recent development of multiple alternatives emphasizes our need to establish treatment algorithms that consider both the likely pathogens and potential toxicities.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Candidiasis; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole; Neutropenia; Opportunistic Infections; Risk Factors

Trichosporon beigelii is a fungus once thought to cause only superficial infections, but recently has been increasingly identified as an opportunistic systemic pathogen in immunocompromised patients. There have been very limited reports of this organism in the burn patient population. We describe the first report of pharmacological management of invasive T. beigelii with a combination of amphotericin B and high dose fluconazole in a burn patient. Antifungal susceptibility testing of T. beigelii determined a change in minimum inhibitory concentrations (MICs) of amphotericin B and a consistent resistance pattern with the use of flucytosine. This paper will review our experience with T. beigelii fungus in a regional burn treatment center and review the literature on other experiences in the burn population.

Topics: Adult; Amphotericin B; Antifungal Agents; Burns; Catheters, Indwelling; Drug Resistance, Microbial; Fatal Outcome; Female; Fluconazole; Flucytosine; Fungemia; Humans; Immunocompromised Host; Male; Mycoses; Opportunistic Infections; Sputum; Trichosporon; Wound Infection

The advent of the human immunodeficiency virus infection and the increasing prevalence of compromised individuals in the community due to modern therapeutic advances have resulted in a resurgence of opportunistic infections, including oral candidoses. One form of the latter presents classically as a white lesion of "thrush" and is usually easily diagnosed and cured. Nonetheless, a minority of these lesions appears in new guises such as erythematous candidosis, thereby confounding the unwary clinician and complicating its management. Despite the availability of several effective antimycotics for the treatment of oral candidoses, failure of therapy is not uncommon due to the unique environment of the oral cavity, where the flushing effect of saliva and the cleansing action of the oral musculature tend to reduce the drug concentration to sub-therapeutic levels. This problem has been partly circumvented by the introduction of the triazole agents, which initially appeared to be highly effective. However, an alarming increase of organisms resistant to the triazoles has been reported recently. In this review, an overview of clinical manifestations of oral candidoses and recent advances in antimycotic therapy is given, together with newer concepts, such as the post-antifungal effect (PAFE) and its possible therapeutic implications.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents, Local; Antifungal Agents; Candida; Candidiasis, Oral; Chlorhexidine; Clotrimazole; Drug Resistance, Fungal; Fluconazole; Flucytosine; Humans; Immunocompromised Host; Itraconazole; Ketoconazole; Miconazole; Mouth; Nystatin; Opportunistic Infections; Saliva; Treatment Failure; Triazoles

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Candidiasis; Catheters, Indwelling; Diagnosis, Differential; Flucytosine; Fusarium; Humans; Iatrogenic Disease; Immunocompromised Host; Mycoses; Opportunistic Infections; Syndrome; Trichosporon

We report a case of cerebral phaeohyphomycosis in a 36-year-old male caused by the neurotropic fungus Ramichloridium obovoideum (Matushima) de Hoog 1977 (Ramichloridium mackenziei Campbell et Al-Hedaithy 1993). This man resided in the Middle East, where the fungus appears to be endemic and, possibly, geographically restricted, since all previous reports of brain abscesses due to this organism have been for patients indigenous to this area. As a servant of the Saudi Arabian royal family, he appeared in the United States seeking treatment for chronic weight loss, fatigue, decreased memory, and a more recent 2-week history of right-hand weakness which worsened to involve the entire right upper extremity. On the day prior to his admission, he had a focal motor seizure with rotation of the head and eyes to the right, followed by secondary generalization. A computerized tomogram showed a ring-enhancing hypodense lesion in the left parietal subcortical region with associated edema and mass effect. Diagnosis of a fungal etiology was made following a parietal craniotomy and excisional biopsy by observation of septate, dematiaceous hyphal elements 2 to 3 microm in width on hematoxylin-and-eosin-stained sections from within areas of inflammation and necrosis. Culture of the excised material grew out a dematiaceous mould which was subsequently identified as R. obovoideum. At two months postsurgery and with a regimen of 200 mg of itraconazole twice a day, the patient was doing well and returned to Saudi Arabia. His condition subsequently deteriorated, however, and following a 7-month course of itraconzole, he expired. We use this case to alert clinicians and personnel in clinical mycology laboratories of the pathogenicity of this organism and its potential occurrence in patients with central nervous system signs and symptoms who have resided in the Middle East and to review and/or compare R. obovoideum with other neurotropic, dematiaceous taxa and similar nonneurotropic, dematiaceous species.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain; Brain Diseases; Female; Humans; Itraconazole; Male; Mitosporic Fungi; Mycoses; Opportunistic Infections; Saudi Arabia; United States

Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Hodgkin Disease; Humans; Male; Middle Aged; Opportunistic Infections

Geotrichum capitatum sepsis are rare, occurring exclusively in immunocompromised patients.. We report the case of a patient with acute leukemia, presenting with chemotherapy-induced neutropenia and hospitalized in an intensive care unit for a severe sepsis. In spite of an antibiotic and antifungal treatment, the patient died of cardiorespiratory failure. Later on, blood cultures proved to be positive for Geotrichum capitatum.. If fungal infections are common in neutropenic patients, Geotrichum capitatum sepsis remain exceptional. The portal of entry is digestive or respiratory, and the invasion is favored by immunodepression and suppression of the normal microbial flora. Induced lesions can be multiorganic. The treatment is not well established, and the association of either amphotericine B and 5-fluorocytosine or amphotericine B and itraconazole would lead to better results. Nevertheless, the prognosis is still unfavorable, with a mortality rate of approximately 75%.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Combinations; Fatal Outcome; Flucytosine; Geotrichosis; Humans; Immunocompromised Host; Itraconazole; Leukemia; Male; Middle Aged; Neutropenia; Opportunistic Infections

The incidence of systemic fungal infection has been increasing during the last two decades. Candida and Aspergillus spp. are the classical opportunistic pathogens. Rare fungi, such as Mucor, Rhizopus, Fusarium, Trichosporon, Paecilomyces, Alternaria, Cladosporium and Pseudoallescheria, are emerging as cause of systemic fungal infection in the immunocompromised host. For more than 40 years Amphotericin B has been the gold standard of antifungal treatment because of its broad spectrum comprising yeasts, dimorphic fungi and moulds. Its nephrotoxicity has led to the development of lipid-associated preparations of amphotericin B: liposomal amphotericin B, amphotericin B colloidal dispersion and amphotericin B lipid complex. These preparations are less nephrotoxic, but higher doses than those of conventional amphotericin B are needed to achieve the same effect. The triazole fluconazole is the treatment of choice in infections caused by Candida albicans. New antifungal compounds are voriconazole and the candins, the pradimicin/benanomycin family, nikkomycin Z and a liposomal preparation of nystatin.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Humans; Mycoses; Opportunistic Infections; Treatment Outcome

The antifungal agents currently available to treat invasive fungal infections are limited in both number and usefulness. Treatment with the polyene amphotericin B (AmB), and with several azoles, in particular fluconazole and itraconazole, is the mainstay of antifungal chemotherapy. However, the clinical usefulness of these drugs is hampered by drawbacks associated with their safety and/or efficacy. There are two approaches to overcome this situation. One is to discover and develop new antifungal agents or formulations with advantages over and/or complementary to existing drugs. For this purpose, the following three categories of new drugs have been the major targets of study and development: (i) lipid formulations of polyenes, (ii) azoles (including cyclodextrin-complexes), and (iii) nonazole compounds, particularly those of microbial origin (antibiotics).

Topics: Amphotericin B; Animals; Antifungal Agents; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Fungi; Humans; Mycoses; Opportunistic Infections; Randomized Controlled Trials as Topic; Triazoles

Mucormycosis historically has caused substantial morbidity with high mortality in renal transplant patients with disseminated and/or rhinocerebral infection and in patients with gastrointestinal illness regardless of predisposing conditions. We report the first successful treatment of gastric mucormycosis in a renal transplant recipient and review presumed pathogenic mechanisms of mucormycosis in renal transplant recipients as well as historical data.

Topics: Amphotericin B; Antifungal Agents; Colonic Diseases; Combined Modality Therapy; Female; Gastrectomy; Humans; Kidney Transplantation; Middle Aged; Mucormycosis; Opportunistic Infections; Pancreatic Diseases; Peritonitis; Risk Factors; Stomach Diseases

Blastomycosis has become increasingly recognized as a serious infection in immunocompromised hosts in recent years. Underlying disorders among these patients include conditions that are typically characterized by abnormalities of T-lymphocyte function such as acquired immunodeficiency syndrome, long-term glucocorticosteroid use, hematologic malignancy, solid organ transplantation, and pregnancy, in addition to a variety of other diseases. Clinically, the disease in immunocompromised patients is potentially much more severe and is characterized by disseminated multiple organ involvement including frequent involvement of the central nervous system. Adult respiratory distress syndrome and/or miliary pulmonary involvement, relatively rare complications in the normal population, are also common in immunocompromised patients. Most notably, mortality as a result of blastomycosis in these patients exceeds 30% and usually occurs within several weeks of presentation. Because of the severity of the disease, initial therapy with amphotericin B is advised for most immunocompromised patients with blastomycosis to gain control of the disease. The role of itraconazole as initial therapy is probably limited to patients with focal, uncomplicated disease. Many of these patients, particularly those with conditions associated with ongoing immunosuppression, require chronic suppressive therapy with an azole to prevent relapsing disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Blastomycosis; Female; Humans; Immunocompromised Host; Infant, Newborn; Itraconazole; Male; Opportunistic Infections; Pregnancy; Prognosis

Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.

Topics: Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Fluconazole; Humans; Middle Aged; Mucormycosis; Opportunistic Infections

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 review of series of > or = 4 cases of invasive aspergillosis (total, 1,223 cases) was undertaken to establish the crude mortality and rate of response to therapy with amphotericin B in the major at-risk host groups. In association with pulmonary, sinus, and cerebral aspergillosis in immunocompromised patients, the crude mortality rates were 86%, 66%, and 99%, respectively. No untreated patient survived. Among 84 patients treated for 1-13 days, only one survived. Among those with invasive pulmonary aspergillosis treated for > or = 14 days, the response rates to amphotericin B deoxycholate were 83% (in cases of heart and renal transplantation), 54% (leukemia), 33% (bone marrow transplantation) and 20% (liver transplantation). Patients with AIDS mostly received both amphotericin B and itraconazole, and 37% of those treated for > or = 14 days responded to therapy. Substantial variation in outcome from series to series was related to underlying disease status, site of disease, and management. Invasive aspergillosis remains a devastating opportunistic infection despite current treatment.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Deoxycholic Acid; Drug Combinations; Humans; Itraconazole; Opportunistic Infections

Infectious complications emerge in more than 80% of neutropenic patients after intensive antineoplastic therapy. Empirical antimicrobial intervention is mandatory, and initial administration of an antipseudomonal betalactam in combination with an aminoglycoside represents the most widely applied standard regimen. At least in patients with short-term neutropenia, also an initial betalactam monotherapy is accepted. Symptoms of skin or venous-catheter-related infection should prompt the addition of a glycopeptide, whereas in case of lung infiltrates, amphotericin B should be administered at least after 96 h. of nonresponse to the antibiotic first-line therapy. In nonresponders with persisting fever of unknown origin, carbapenems or fluoroquinolones in combination with a glycopeptide might be considered for second-line treatment. The supplementation of a recombinant hematopoietic growth factor [G-CSF or GM-CSF] shows no significant benefit and should be restricted to controlled clinical studies. In case of good clinical response, the established antimicrobial treatment regimen should be continued for at least seven days in persistently neutropenic patients.

Topics: Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Drug Therapy, Combination; Glycopeptides; Hematopoietic Cell Growth Factors; Humans; Lactams; Neutropenia; Opportunistic Infections

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

Invasive aspergillosis of the central nervous system is a rare but well-described disease. There have been only a few reported survivors, and mortality exceeds 95% in the immunosuppressed host. We present a 2-year-old boy with acute lymphatic leukemia and multiple Aspergillus brain abscesses who was successfully treated with liposomal amphotericin B, itraconazole, and surgical excision of the abscesses. Liposomal amphotericin B is a new preparation that safely allows the attainment of significantly higher tissue levels with less toxicity than standard amphotericin B. The treatment of patients with invasive central nervous system aspergillosis is reviewed.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus fumigatus; Brain Abscess; Child, Preschool; Combined Modality Therapy; Drug Carriers; Drug Therapy, Combination; Humans; Itraconazole; Liposomes; Male; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We report a clinical case of severe medullary aplasia complicated by fungal antritis. The treatment adopted for this patient consists in a clean operation of the infective focus and the local instillation of Amfotericina B during the post operative period. In this way the systemic circulation is not interested by the use of Amfotericina B, which is extremely important to avoid the inevitable onset of several unwanted side-effects; besides, we avoid the progression of the infective focus and its systemic diffusion.

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus flavus; Bone Marrow Diseases; Combined Modality Therapy; Fusarium; Humans; Immunosuppression Therapy; Male; Mycoses; Opportunistic Infections; Recurrence; Sinusitis

During the last years, the proportion of cancer patients who develop systemic fungal infections has increased steadily. These infections are characterised by high mortality, especially in patients with persistent granulocytopenia and in those receiving allogeneic bone marrow transplants. The most important pathogens in neutropenic patients are Candida and Aspergillus spp. Usually, Candida infections arise from overgrowth in the gastrointestinal tract, while Aspergillus infections are acquired by inhalation of spores. Prophylaxis of systemic fungal infections seems mandatory since optimal strategies for diagnosis and treatment of these infections are lacking. Treatment with the non-absorbable polyenes nystatin and amphotericin B is useful for prophylaxis of superficial fungal infections, provided that compliance of the patients is optimal. The imidazoles ketoconazole and miconazole can reduce the incidence of superficial fungal infections, but there are conflicting data regarding their value for prevention of systemic mycoses. There are several studies indicating that prophylactic use of fluconazole reduces the incidence of mucosal and systemic fungal infections, especially in patients receiving allogeneic bone marrow transplants. Fluconazole shows reduced activity against several Non-albicans spp. and is not active against Aspergillus spp. Itraconazole has in vitro and in vivo activity against several Aspergillus spp. but high serum and tissue levels are necessary. However, bioavailability of itraconazole is reduced in patients with raised gastric pH and no i.v. formulation is available. Although there is some evidence for its prophylactic activity against Aspergillus infections in neutropenic patients, more studies are necessary to confirm these findings. Intravenous amphotericin B cannot be recommended for routine prophylactic use because of its toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Fluconazole; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections

Deep seated candidosis are the most common invasive fungal infections occurring in various categories of patients including those with cancer, burns as well as patients with AIDS or undergoing organ transplantation. Various clinical entities have to be distinguished with implications for diagnostic procedures as well as for adequate therapy. During the last decade, tremendous progress has been achieved leading to a major reduction of mortality attributable for candidaemia from 80% (in the seventies) to 40% in the nineties, mainly due to early empiric antifungal and better prophylaxis treatment. Other antifungal strategies than conventional amphotericin B are now available and have been shown effective, in particular, new modalities to administer amphotericin B including various lipid formulations, but also new azoles and mainly the triazoles such as fluconazole and itraconazole. Fluconazole has been shown effective as prophylaxis of candidosis including in patients undergoing bone marrow transplantation as well as in treatment of oropharyngeal candidosis and for candidaemia occurring in non-neutropenic patients. More limited data are available on itraconazole so far in particular in patients with documented invasive candidosis, but preliminary reports are encouraging. Oral therapy with systemic efficacy is more easy to recommend and allows ambulatory treatment. Candidosis is not a benign disease and in every single patient with fungemia antifungal treatment is mandatory.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Fluconazole; Humans; Incidence; Itraconazole; Neoplasms; Opportunistic Infections; Postoperative Complications; Transplantation

Topics: Allopurinol; Amphotericin B; Antimony; Humans; Immunity, Cellular; Leishmaniasis, Visceral; Opportunistic Infections

We report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well-documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico-pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.

Topics: Amphotericin B; Child, Preschool; Female; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Multiple Myeloma; Mycoses; Opportunistic Infections; Treatment Outcome

Invasive aspergillosis is generally a life-threatening invasive opportunistic mycosis affecting principally the upper and lower respiratory tract. Therapeutic response rates vary considerably from one host group to another with particularly high mortality rates in bone marrow transplant, liver transplant and patients with aplastic anaemia or AIDS. Only two drugs are useful for therapy, amphotericin and itraconazole. Recent advances in the formulation of amphoterin B (AmBisome and Amphocil) have resulted in intravenous preparations with lower toxicity, particularly nephrotoxicity, but it has yet to be shown that they have an increased therapeutic index for the treatment of invasive aspergillosis. Itraconazole can only be used orally and in some particularly high-risk or critically ill patients adequate serum concentrations cannot be achieved. The addition of flucytosine or rifampicin to amphotericin B therapy has, at best, only a marginal benefit. Surgery is essential for some manifestations of invasive aspergillosis. This article reviews therapeutic strategies including criteria for initiation of therapy, combination and sequential therapy, duration of therapy and secondary prophylaxis and indications for surgery in invasive aspergillosis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Cholesterol Esters; Drug Carriers; Drug Therapy, Combination; Flucytosine; Humans; Immunocompromised Host; Infusions, Intravenous; Itraconazole; Liposomes; Opportunistic Infections; Rifampin

Cryptococcal infection is the most common fungal infection of the central nervous system. More than 50% of the cases of cryptococcal infection are superimposed on an immunosuppressive or other general debilitating condition. Cerebral cryptococcosis usually presents as meningitis or meningoencephalitis, although cerebral granuloma has also been reported. Hydrocephalus is the most common neurosurgical complication of cerebral cryptococcosis. The majority of patients require only medical treatment with antifungal drugs. However, when complications ensue, surgical intervention is mandatory. We suggest that chronic meningitis be ruled out in all patients prior to the placement of shunts. In the two cases reported here treatment of cryptococcal meningitis was a combination of amphotericin B and flucytosine for six weeks. Fluconazole is a new alternative and at least as effective as amphotericin B.

Topics: Adolescent; Adult; Agammaglobulinemia; Amphotericin B; Brain Abscess; Brain Diseases; Cryptococcosis; Female; Flucytosine; HIV Seronegativity; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Opportunistic Infections

Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cytokines; Drug Administration Routes; Humans; Imidazoles; Neoplasms; Opportunistic Infections; Polyenes; Triazoles

Topics: Amphotericin B; Animals; Cross Infection; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Flucytosine; Humans; Opportunistic Infections

Pregnant women with respiratory symptoms of pleuritic pain and productive cough should undergo evaluation for coccidioidomycosis. This should include a history of travel or residency in endemic areas and careful assessment for toxic erythema, erythema nodosum, or erythema multiforme. To confirm a diagnosis of this disease, a sputum culture, wet mount, and serological tests should be performed. The risk of dissemination, which is highest in the second and third trimesters, can be estimated by a complement-fixation titer. In disseminated cases aggressive treatment with amphotericin B has improved the previously reported high maternal and neonatal mortality rate. Fortunately, case reports do not indicate that transplacental spread occurs. Reactivation or exacerbation of a chronic low-grade infection during pregnancy may occur in patients treated for prior disseminated disease (32, 34). Interestingly, both of the reported cases of reactivation or exacerbation occurred in insulin-dependent diabetics.

Topics: Adult; Amphotericin B; Coccidioidomycosis; Diabetes Mellitus, Type 1; Erythema Multiforme; Erythema Nodosum; Female; Fetal Death; Humans; Insulin Infusion Systems; Opportunistic Infections; Pregnancy; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Pregnancy Trimester, Second

Systemic fungal infections are an important cause of morbidity and mortality among immunocompromised patients. New antifungal agents, such as triazoles, are now available, and the place of in vitro tests has to be discussed. It has been shown that interlaboratory reproducibility of in vitro susceptibility tests against fungi was low, due to the lack of standardization. Recently, the NCCLS defined conditions permitting a good interlaboratory reproducibility. However, the predictive value of in vitro susceptibility tests on the therapeutic outcome remain to be demonstrated, and is now under investigation. At the present time, susceptibility testing can be useful: in patients treated by amphotericin B for a severe fungal infection and who do not improve under therapy; to detect resistance to 5-fluorocytosine; to compare the sensitivity to triazoles before and after treatment, in case of therapeutic failure. Serum levels monitoring is useful to prevent the toxicity due to 5-fluorocytosine and to control the digestive absorption of triazoles, especially the lipophilic compound itraconazole.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; In Vitro Techniques; Itraconazole; Ketoconazole; Opportunistic Infections

Phaeohyphomycosis caused by Exophiala species is an unusual infection, but it has been reported with increasing frequency as immunosuppressive therapy has become more widespread and laboratory methods for diagnosis have improved. To our knowledge, the first case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in a cardiac transplant patient is presented, and previously reported cases of exophiala infection are reviewed. This patient was successfully managed with surgical excision of the lesion and combination therapy with amphotericin B and 5-fluorocytosine.

Topics: Adult; Amphotericin B; Combined Modality Therapy; Drug Administration Schedule; Drug Therapy, Combination; Exophiala; Flucytosine; Heart Transplantation; Humans; Immunosuppression Therapy; Male; Mycoses; Opportunistic Infections

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: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Dermatomycoses; Diagnosis, Differential; Fluconazole; Humans; Injections, Spinal; Meningitis; Molluscum Contagiosum; Opportunistic Infections; Prognosis

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Product Surveillance, Postmarketing; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Because deep opportunistic mycoses are relatively rare, clinicians frequently lack routine in the application of antimycotics. It is the purpose of this review to summarize, from a practical point of view, rationale, indications, applications and toxicity of antimycotic therapy for the mycoses autochthonous to Europe. Amphotericin B remains the standard therapy for most deep opportunistic mycoses, while the newer azoles are the first line agents to be used for superficial forms of candidiasis.

Topics: Amphotericin B; Antifungal Agents; Azoles; Drug Therapy, Combination; Humans; Mycoses; Opportunistic Infections

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Female; Fusarium; Humans; Mycoses; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin; Skin; Spider Bites; Staphylococcal Infections

Candida lusitaniae has been an infrequently reported opportunistic pathogen. Most previously reported cases of serious infection caused by this organism have proven fatal and were associated with amphotericin resistance of the organism. We report two patients with hematologic malignancies undergoing cytotoxic chemotherapy who developed fungemia with this organism while they were granulocytopenic. The organisms isolated from each patient were fully susceptible and were treated successfully with amphotericin B. When isolated from an immunocompromised host, C. lusitaniae should be considered an opportunistic pathogen and undergo antifungal susceptibility testing. Amphotericin B should be considered the drug of choice, but a poor clinical response may be indicative of a resistant isolate.

Topics: Adult; Amphotericin B; Candida; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Opportunistic Infections

C. albicans and its related species have become major nosocomial causes of morbidity and mortality in the immunocompromised and in other severely ill patients. Diagnosis of the severe forms of the disease remains difficult and depends on the basis of a composite of clinical findings. Treatment for most forms of severe Candida infections remains amphotericin B despite its toxicities. Until more effective prevention of the disease becomes feasible, Candida infections are likely to increase in frequency as major iatrogenic problems.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Candidiasis; Humans; Immune Tolerance; Opportunistic Infections

Disseminated trichosporonosis due to Trichosporon beigelii is an uncommon but increasingly reported infection in immunocompromised patients. It often presents as fungemia, cutaneous lesions, pulmonary infiltrates, and azotemia. This systemic mycosis is often refractory to conventional antifungal therapy and is frequently fatal.

Topics: Amphotericin B; Antifungal Agents; Humans; Immune Tolerance; Mycoses; Opportunistic Infections; Trichosporon

Zygomycosis represents an excellent example of an opportunistic fungal infection that generally occurs in the debilitated, immunocompromised, or acidotic host. Infections are usually fulminant, with etiologic agents exhibiting predilection for invasion of blood vessels with resultant infarction and necrosis. The spectrum of agents capable of inciding zygomycosis has broadened and the incidence has increased in contemporary medicine. Nevertheless, an increased index of suspicion, better mycological acumen, aggressive surgical debridement of diseased tissue, and prompt therapy with amphotericin B have rendered substantial improvement in the prognosis of an otherwise fatal infectious disease. Rapid and accurate diagnostic techniques and the availability of less toxic, efficacious antifungal agents should be sought after goals for the enhanced management of zygomycosis.

Topics: Amphotericin B; Antifungal Agents; Humans; Immune Tolerance; Mucormycosis; Opportunistic Infections

C tropicalis is a frequent and virulent pathogen in neutropenic patients. Infection control personnel should be familiar with this microorganism and the significance of a positive culture for C tropicalis in a setting of poor host resistance.

Topics: Amphotericin B; Candida; Candidiasis; Humans; Neutropenia; Opportunistic Infections

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections

Fungal infections in immunocompromised hosts cause major morbidity and mortality. The Candida and Aspergillus species are the most common causes, but many rarer organisms, once considered "contaminants," are being reported. The number of patients who receive immunosuppressive agents for the treatment of malignancy or for organ transplantation is increasing as well as the potential for local or disseminated fungal infections. The diagnosis of these infections is often difficult and the existing methods for treatment are often ineffective. A high degree of suspicion to identify fungal infections and to prompt initiation of treatment must be maintained if the survival rate of these patients is expected to improve.

Topics: Amphotericin B; Dermatomycoses; Flucytosine; Humans; Immunosuppression Therapy; Ketoconazole; Opportunistic Infections

Systemic candidiasis is a disease of increasing incidence and proportions, which appears to be associated with the advances in modern medicine. It involves primarily patients with severe debilitating and malignant disease who are receiving immunosuppressive, cytotoxic, antimetabolite, and antibiotic therapy. Side effects of these otherwise major therapeutic agents predispose patients to opportunistic fungal infections, of which candidiasis is the most common. The high morbidity and mortality of disseminated candidiasis in neutropenic patients are difficult obstacles to obtaining the optimal, if not full, potential of modern chemotherapy for cancer. The inability to diagnose early invasive and systemic candidiasis is a major handicap that delays timely initiation of antifungal therapy. The paucity of highly efficacious antifungal agents with low toxicity severely limits the ability to successfully cure systemic fungal infections in cancer patients. Aggressive research into the basic biology of Candida spp. is necessary for directing the development of better diagnostic methods and improved antifungal drugs.

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Immune Tolerance; Ketoconazole; Neoplasms; Opportunistic Infections; Risk Factors

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Cryptococcosis; Histoplasmosis; Humans; Immune Tolerance; Immunity, Cellular; Mycoses; Opportunistic Infections

Seven cases of successfully treated Candida albicans cerebrospinal fluid shunt infections are reported. Treatment consisted of shunt removal and intravenous Amphotericin B in all cases and intraventricular Amphotericin B in 4 cases. Serious underlying medical illness, recent antibiotic therapy, indwelling intravascular and/or Foley catheters, coincident candidiasis and low birth weight prematurity are major risk factors for candida shunt infection. Candida shunt infection appears to occur by either contamination at the time of shunt placement or by hematogenous dissemination.

Topics: Adolescent; Aged; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Catheters, Indwelling; Cerebrospinal Fluid Shunts; Equipment Contamination; Female; Humans; Infant, Newborn; Infant, Premature; Male; Opportunistic Infections; Risk Factors; Sepsis; Surgical Wound Infection

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

Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Caspofungin; Child; Child, Preschool; Echinocandins; Female; Fever of Unknown Origin; Hospitalization; Humans; Infant; Length of Stay; Lipopeptides; Male; Mycoses; Neutropenia; Opportunistic Infections; Patient Selection; Prospective Studies; Treatment Outcome

Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment.. Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines.. Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm.. A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fever; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Prospective Studies; Pyrimidines; Radiography, Thoracic; Risk Factors; Singapore; Tomography, X-Ray Computed; Treatment Outcome; Triazoles; Voriconazole

Nebulized amphotericin B deoxycholate (n-ABD) is used to prevent Aspergillus infection in lung transplantation. Nebulized liposomal amphotericin B (n-LAB) is another option; however, no clinical data are available on the results of n-LAB for this purpose.. In an observational study performed in 2 centers to assess the feasibility, tolerability, and outcomes of n-LAB prophylaxis, 104 consecutive patients undergoing prophylaxis with n-LAB were compared with 49 historical controls who received n-ABD. Patient follow-up lasted 12 months. The n-LAB prophylaxis regimen was 25 mg thrice weekly starting on the first post-operative day and continuing to 60 days, 25 mg once weekly from 60 to 180 days, and the same dose once every 2 weeks thereafter.. Aspergillus infection developed in 8 of 104 patients (7.7%) with n-LAB prophylaxis (5 colonization, 1 simple tracheobronchitis, 1 ulcerative tracheobronchitis, and 1 invasive pulmonary infection). Ulcerative tracheobronchitis and invasive pulmonary aspergillosis were regarded as invasive disease; hence, the rate of invasive disease was 1.9% (2 patients). The control group had similar rates of Aspergillus infection (10.2%; p = 0.6) and invasive disease (4.1%; p = 0.43). In 3 patients (2.9%), n-LAB was withdrawn due to bronchospasm in 2 and nausea in 1. In the control group, prophylaxis was stopped in 2 patients (4.1%) because of bronchospasm (p = 0.7).. At the dose and frequency described, n-LAB seems effective, safe, and convenient for the prevention of Aspergillus infection in lung transplant patients.

Topics: Administration, Inhalation; Adult; Amphotericin B; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Immunosuppressive Agents; Liposomes; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pulmonary Aspergillosis

Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs.. In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia.. The median duration of neutropenia (neutrophil count, <500 cells/mm3) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; P < .05), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; P < .01). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%.. Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.

Topics: Adult; Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Chi-Square Distribution; Deoxycholic Acid; Drug Combinations; Female; Fever; Humans; Male; Middle Aged; Multicenter Studies as Topic; Mycoses; Neutropenia; Opportunistic Infections; Risk Factors; Statistics, Nonparametric

Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients.. In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups.. Significantly fewer itraconazole patients discontinued treatment due to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001). The main reason for discontinuation was a rise in serum creatinine (1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability.. Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cross-Over Studies; Empiricism; Female; Fever of Unknown Origin; Germany; Hematologic Neoplasms; Humans; Infusions, Intravenous; Itraconazole; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Patient Dropouts; 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 test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion.. Randomised, controlled, non-blinded, single centre study.. University hospital providing tertiary clinical care.. 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections.. Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours.. Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis.. Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months' follow up in the rapid infusion than in the continuous infusion group.. Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Prospective Studies; Survival Rate

Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting.. To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.. An open randomized, controlled, multicenter trial, powered for equivalence.. 60 oncology centers in 10 countries.. 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy.. Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.. Defervescence, breakthrough fungal infection, drug-related adverse events, and death.. For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days.. Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Fluconazole; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Colloids; Cyclosporine; Double-Blind Method; Female; Fever; Humans; Immunosuppressive Agents; Infant; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Survival Analysis; Treatment Outcome

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Fever; Fluconazole; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Mycoses; Neoplasms; Opportunistic Infections; Prospective Studies; Treatment Outcome

A randomized, double-blind, placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation. During prophylaxis, systemic fungal infections occurred in 10 (7%) of 152 fluconazole-treated patients compared with 26 (18%) of 148 placebo-treated patients (P = .004). There were no Candida albicans infections in fluconazole recipients compared with 18 in placebo recipients (P < .001) and no significant increase in Candida infections other than C. albicans. Fluconazole also significantly reduced the incidence of superficial fungal infections (P < .001), fungal colonization (P = .037), and empiric amphotericin B use (P = .005). The probability of survival was improved in fluconazole recipients, in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients (P = .004). No clinically significant toxicity was detected with fluconazole use. Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation.

Topics: Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Candida; Candidiasis; Double-Blind Method; Drug Resistance, Microbial; Female; Fluconazole; Humans; Male; Middle Aged; Opportunistic Infections; Patient Compliance; Prospective Studies; Survival Analysis

Eighty-six consecutive liver transplant recipients were prospectively randomized in a double-blind, placebo-controlled antifungal prophylaxis study. Seventy-seven patients received 5 days of prophylaxis starting during the transplantation with either liposomal amphotericin B (AmBisome) 1 mg/kg/day or placebo. Among 40 AmBisome-treated patients, no invasive Candida infection was seen during the first month, compared with 5 invasive Candida albicans infections among 37 control patients (P < 0.05). Furthermore, 1 placebo patient experienced Aspergillus niger pneumonia. Thus, the overall incidence of invasive fungal infections was 0/40 (0%) in the AmBisome group versus 6/37 (16%) in the placebo group (P < 0.01). Patient survival at 30 days was 92% versus 94% for AmBisome- and placebo-treated patients, respectively. One patient experienced backache related to AmBisome infusion. Two patients had transient thrombocytopenia possibly caused by AmBisome treatment. AmBisome was otherwise well tolerated. The total cost for all antifungal drugs used in both groups was equal. However, prophylaxis with AmBisome was $5000 less expensive than treatment of proven invasive fungal infections among placebo patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Aspergillus niger; Candidiasis; Costs and Cost Analysis; Double-Blind Method; Drug Carriers; Female; Humans; Immunosuppressive Agents; Kidney Function Tests; Liposomes; Liver Function Tests; Liver Transplantation; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections

We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment.. The trial was a prospective, randomized, and non-blinded study.. The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands.. Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis.. Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients.. Outcome measures were a complete or partial response, recrudescence and relapse.. A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003).. Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Flucytosine; Humans; Itraconazole; Ketoconazole; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Prospective Studies; Survival Analysis

Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.

Topics: Adult; Aerosols; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Female; Humans; Immunocompromised Host; Incidence; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Opportunistic Infections; Pilot Projects

To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis.. Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses.. Los Angeles County-University of Southern California Medical Center.. Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis.. Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27).. Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis; Opportunistic Infections; Prospective Studies; Randomized Controlled Trials as Topic

This report is a survey of epidemiological facts about oro-gastro-intestinal tract mycoses. It is documented that children and older people suffer more often from oro-gastro-intestinal tract mycoses than the rest of the average population. In addition older patients with oro-gastro-intestinal tract mycoses show predisposing factors more frequently than younger people.

Topics: Adolescent; Adult; Aged; Amphotericin B; Candidiasis, Oral; Child; Child, Preschool; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Infant; Middle Aged; Mycoses; Opportunistic Infections

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare, virally-induced malignancies that occur almost exclusively in immunocompromised individuals. We report a very rare case of a dura-based EBV-SMT with superimposed local cryptococcal infection.. An adult male with a history of untreated acquired immunodeficiency syndrome presented to our hospital with worsening headaches, diarrhea, and diffuse myalgias.. Blood cultures were positive for methicillin-resistant Staphylococcus aureus and Cryptococcus neoformans serum antigen. Magnetic resonance imaging revealed 2 adjacent enhancing masses in the right temporal lobe, perilesional edema, and mass effect of the right lateral ventricle. Histological examination and immunohistochemical stains of the surgical specimen were consistent with EBV-SMT. Cryptococcus organisms were identified within the neoplasm.. The patient underwent complete tumor resection, received an extended course of amphotericin and flucytosine, and was restarted on antiretroviral therapy.. The patient was discharged from the hospital with no focal neurological deficits.. Epstein-Barr virus associated smooth muscle tumors are rare malignancies that occur in immunocompromised patients. Prognosis is largely dependent on immune reconstitution and treatment of concomitant infections.

Topics: Adult; Amphotericin B; Antiretroviral Therapy, Highly Active; Cryptococcus neoformans; Epstein-Barr Virus Infections; Flucytosine; Herpesvirus 4, Human; HIV Infections; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Methicillin-Resistant Staphylococcus aureus; Opportunistic Infections; Smooth Muscle Tumor; Superinfection; Temporal Lobe

Cutaneous mucormycosis is an emerging opportunistic mycosis caused by Mucorales. It can be divided into primary caused by trauma and secondary by extension of rhino-cerebral and disseminated cases. The objective is to present a retrospective study of cases of mucormycosis with cutaneous involvement.. A retrospective and descriptive study was carried out. Mucormycosis patients were included and divided into two groups: a) Primary Cutaneous and b) Secondary Cutaneous. Mycological tests were performed; the agents were identified by morphology and molecular studies (PCR and sequencing); some cases underwent histopathology. Clinical data and response to treatment were collected.. 115 cases were included, 18 of primary, and 97 of secondary cutaneous mucormycosis. Primary cutaneous mucormycosis was most associated with adhesive bands (44.4%) and trauma from traffic accidents (33.3%). The principal clinical form was extensive and deep necrotic ulcers. Secondary cutaneous mucormycosis cases were rhino-cerebral with uncontrolled diabetes (81.4%) The most frequent clinical presentation was necrosis of the eyelid and the nose (65.9%). In both groups, the principal agent was Rhizopus arrhizus, 38.8% and 74.2% respectively. The most effective treatment was the combination of amphotericin B with surgical debridement. The clinical and mycological cure was achieved in 31.0% of primary cases, and 44.4% for secondary cases.. Primary cutaneous mucormycosis is caused by implantation of the Mucorales due to trauma or rupture of the cutaneous barrier-breach, and secondary cutaneous mucormycosis develops as part of the rhino-cerebral process. The response to treatment depends on the extension and depth, as well as the predisposing factors.

Topics: Adhesives; Adult; Amphotericin B; Antifungal Agents; Debridement; Dermatomycoses; Diabetes Complications; Female; Humans; Male; Mexico; Middle Aged; Mucormycosis; Opportunistic Infections; Retrospective Studies; Rhizopus oryzae; Tertiary Care Centers; Wounds and Injuries

Mucorales are opportunistic pathogens that can cause life-threatening diseases predominantly in immunocompromised patients.. This study aimed to investigate the frequency, seasonal variation and antifungal susceptibility of pathogenic Mucorales in the soil collected from seven hospitals in Urmia, Iran, between November 2017 and July 2018 in four different seasons.. Mucorales isolates obtained from soil were characterised based on conventional and molecular assays. In addition, in vitro antifungal susceptibility was performed using the CLSI M38Ed3 procedure.. Out of 196 tested soil samples, 80 (40.8%) samples were positive for mucoralean fungi. Rhizopus arrhizus var. arrhizus (n = 47) was the most frequent species followed by Mucor circinelloides (n = 21) and Cunninghamella echinulata (n = 6). A seasonal variation in the frequency of Mucorales in soil was detected with a maximum of culture-positive soil samples detected in wet autumn (43.2%) followed by winter (23.4%), summer (19.7%) and spring (13.6%). In vitro antifungal susceptibility testing for 80 environmental isolates exhibited MIC of ≤2 μg/ml for amphotericin B indicating the smallest range of MIC variation among the tested Mucorales (range: 0.125-2 μg/ml). Among the azoles, posaconazole was the most effective antifungals (GM MIC, 0.724 μg/ml).. We considered associations of species and seasonal frequencies between soil mucoralean fungi and mucormycosis. The effect of opportunistic Mucorales dominating in the soil and prevalent causative agents of mucormycosis in Iran reported in the literatures but more comprehensive studies are needed to confirm this conclusion.

Topics: Amphotericin B; Antifungal Agents; Cunninghamella; Hospitals; Humans; Iran; Microbial Sensitivity Tests; Mucor; Mucorales; Mucormycosis; Opportunistic Infections; Rhizopus; Seasons; Soil; Soil Microbiology; Triazoles

Solid organ transplant recipients are vulnerable to various unusual infections. Visceral Leishmaniasis (VL) is a protozoal opportunistic infection, which may affect the immune-suppressed hosts and solid organ transplant recipients. The BK virus infection is an evolving challenge in kidney transplant recipients. However, there are very few reports of BK virus (BKV) nephropathy involving the native kidney in liver transplant recipients. To the best of our knowledge, this is the first report of the simultaneous occurrence of these rare infections in a liver transplant recipient.. The patient was a 9-year-old girl, a case of liver transplantation who presented with the incidental finding of proteinuria, azotemia, and cytopenia. Investigations revealed that she had concomitant BKV nephropathy and visceral leishmaniasis. Both infections were successfully treated.. BK virus should be considered as a cause of nephropathy in liver transplant recipients. The presenting features of fever, cytopenia, and splenomegaly in a post-transplant patient should remind of unusual infections such as VL other than the common post-transplant conditions.

Topics: Amphotericin B; Antihypertensive Agents; Antiprotozoal Agents; BK Virus; Child; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Incidental Findings; Leishmaniasis, Visceral; Liver Transplantation; Opportunistic Infections; Polyomavirus Infections; Tumor Virus Infections; Viral Load

Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that have a minor effect on

Topics: Amphotericin B; Animals; Antifungal Agents; Auranofin; Candida albicans; Candidiasis; Cell Line; Ciclopirox; Cryptococcosis; Cryptococcus neoformans; Drug Evaluation, Preclinical; Drug Repositioning; Drug Synergism; Erythromycin; Flucytosine; Humans; Mice; Microbial Sensitivity Tests; Opportunistic Infections; RAW 264.7 Cells; Zebrafish

Topics: Amphotericin B; Antifungal Agents; Brentuximab Vedotin; Cryptococcus neoformans; Dexamethasone; Flucytosine; Hodgkin Disease; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections

Talaromycosis (penicillinosis) is multiresistent opportunistic mycosis. The infection can be inapparent and it can simmulate malignant tumor dissemination in some patients.. We present a case of 33-years-old patient with mucinous adenocarcinoma of left ovary, initially FIGO IIC. The patient had had hysterectomy, bilateral adnexectomy, omentectomy and port-site metastasis extirpation. Six cycles of 1st chemother-apy paclitaxel and carboplatin had been administered to patient follow-ing the surgery. Positron emission tomography / computed tomography (PET/CT) scan after the treatment, had shown metabolic activity infiltrat-ing both lung apexes, supposedly with no dis-ease correlation, and hypermetabolic foci in spleen, suspicious of be-ing metastases. Pa-cient showed no clinical symp-toms, nor markers of inflammation elevation. Initially elevated serum tumor markers CA125 and CA72-4 had decreased after the treatment. Bronchoalveolar lavage cytology described presence of inflammatory infiltration with fungiform-ing hyphae - most probably an aspergillosis. Mannan and galactomannan serology was negative. In regard to splenectomy plans, treatment with voriconazol was initiated empirically. Result of fungi cultivation out of bronchoalveolar lavage was finalized later, show-ing sporadic presence o Penicillium sp. with resistance to antimycotic treatment except for amphotericin B. Liposomal amphotericin B treatment was administered in two cures, 28 days in total. Immunomodulatory treatment of secondary cellular immunodeficiency and vaccination against encapsulated bacteria was given to the patient. Splenectomy was performed 6 months after the end of chemother-apy treatment. Histopathology showed chronic granulomatous inflammation without mycotic hyphae, with no evidence of tumor cells. After the splenectomy, patient was treated by surgical incision and drainage and by klindamycin for intraabdominal abscess in left hypogastric area.. Patient is under follow up by oncologist, immunologist and gynecologist 12 months after the splenectomy, she is surveilled by PET/CT and serum tumor markers. Talaromycosis can be clinically inapparent in spite of its dissemination. It can be present in diffuse, granulomatous and mixed form. Therapeutic agent is sometimes limited to amphotericin B due to its resistence. Liposomal form of amphotericin B is recommended regard-ing its pharmacokinetic properties. In case of dissemination, administration period of more than 14 days is recommended, even in inapparent form. Immunomodulatory treatment is recommended due to opportunistic infection.

Topics: Adenocarcinoma, Mucinous; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Multiple, Fungal; Female; Humans; Mycoses; Opportunistic Infections; Ovarian Neoplasms; Penicillium; Splenectomy; Splenic Neoplasms

Curvularia is a saprophytic dematiaceous mold and a rare human pathogen. Here, we report three severely immunocompromised pediatric patients who developed invasive Curvularia infection. Diagnosis was achieved or confirmed in all cases by fungal ribosome sequencing, which hastened species identification and targeted treatment for the patients reported. There are no treatment guidelines for invasive Curvularia infection, though we report three patients who were cured of their infection through a combination of surgical resection and various anti-fungal therapies, indicating a relatively low virulence and good prognosis in comparison to other angioinvasive molds.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Child; Dermatomycoses; Female; Humans; Immunocompromised Host; Male; Opportunistic Infections; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; RNA, Ribosomal, 28S; Sequence Analysis, DNA; Voriconazole

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

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cancer Care Facilities; Child; Child, Preschool; Egypt; Female; Hematologic Neoplasms; Hospitals, Pediatric; Humans; Immunocompromised Host; Male; Mucormycosis; Neoplasms; Opportunistic Infections; Retrospective Studies; Risk Factors; Treatment Outcome; Triazoles

Topics: Adult; Amphotericin B; Antifungal Agents; Cavernous Sinus Thrombosis; Debridement; Delayed Diagnosis; Diabetes Complications; Humans; Magnetic Resonance Imaging; Male; Mucormycosis; Ophthalmoplegia; Opportunistic Infections; Orbit Evisceration; Orbital Cellulitis; Sinusitis; Triazoles

Cryptococcal meningitis is an opportunistic infection predominantly affecting immunocompromised patients but rarely can affect the immunocompetent. We describe a 53-year-old Caucasian man who presented complaining of a 2-week history of severe bilateral eye pain and diplopia. His only known risk factor was that he lived in a horse farm and recently shot bats and pigeons in his barn. He visited an outside hospital during this time without a diagnosis established. After further deliberation, we obtained a lumbar puncture (LP) which revealed an opening pressure (OP) of 27 cm H

Topics: Agricultural Workers' Diseases; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Diplopia; Drug Therapy, Combination; Eye Pain; Fluconazole; Humans; Immunocompetence; Male; Meningitis, Cryptococcal; Meningoencephalitis; Middle Aged; Opportunistic Infections; Rare Diseases

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

Mucormycosis is a rare but fulminant opportunistic fungal infection, which occurs most often in diabetic and immunocompromised patients. Dental extractions may create a portal of entry for the fungal infection. The mucormycosis may be the original cause of the pain and can be misdiagnosed as dental pain. In this paper, two cases of mucormycosis are reported after dental extractions and successfully treated with amphotericin B (case #1) and combined with posaconazole (case #2). The two cases we describe exemplify the fulminant mucormycosis of maxillary sinuses after dental extraction inpatients with uncontrolled diabetic support the findings that this predisposing condition created a suitable environment for the Mucorales growth. These case reports emphasize early recognition and urgent treatment of mucormycosis is necessary to prevent the spread of infection Therefore, dental surgeons and healthcare practitioners should become familiar with mucormycosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Diabetes Complications; Diabetes Mellitus; Female; Humans; Immunocompromised Host; Male; Maxillary Sinus; Middle Aged; Mucorales; Mucormycosis; Opportunistic Infections; Sinusitis; Tooth Extraction; Treatment Outcome; Triazoles

Topics: Amphotericin B; Antifungal Agents; Apoptosis; Biofilms; Cell Membrane; Cell Membrane Permeability; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; DNA Fragmentation; Ergosterol; Fungal Capsules; Humans; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Opportunistic Infections; Phosphorylcholine; Plankton; Reactive Oxygen Species

Histoplasma microconidia when inhaled are presented in antigenic form to T cells, limiting the extent of infection; however, defects in cellular immunity results in disseminated disease. Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder resulting in functionally impaired lymphocytes, predisposing patients to various opportunistic infections. The author reports a recently treated patient with CLL presenting with constitutional symptoms accompanied by hepatosplenomegaly and diffuse adenopathy. Considering the recent diagnosis and treatment of CLL, initial suspicion was relapsed disease. However, considering the immune deficiency associated with CLL and its treatment, infectious aetiologies were strongly considered. Further investigation revealed a case of disseminated histoplasmosis mimicking CLL in this reported patient. Considering appropriate diagnosis and timely therapy, the reported patient had good prognosis despite being diagnosed with disseminated histoplasmosis. This case highlights consideration of disseminated histoplasmosis in patients presenting with diffuse adenopathy along with hepatomegaly and/or splenomegaly in the right clinical setting.

Topics: Aged; Amphotericin B; Antifungal Agents; Farmers; Fever; Hepatomegaly; Histoplasmosis; Humans; Itraconazole; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Opportunistic Infections; Radionuclide Imaging; Splenomegaly; Tomography, X-Ray Computed; Treatment Outcome; Urinalysis; Weight Loss

Topics: Amphotericin B; Duodenal Ulcer; Female; Gentamicins; Humans; Infections; Middle Aged; Opportunistic Infections; Peritoneal Cavity; Peritonitis; Prototheca; Schizophrenia, Paranoid; Soil Microbiology

The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis.\ A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed.\ A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma.\ Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a “watch and wait” basis.\ Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Topics: Aged, 80 and over; Alzheimer Disease; Amphotericin B; Antifungal Agents; Diabetes Mellitus, Type 2; Female; Histoplasma; Histoplasmosis; Humans; Hypertension; Itraconazole; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Opportunistic Infections; Watchful Waiting

Topics: Adult; Amphotericin B; Biopsy, Needle; Chronic Disease; Debridement; Diagnosis, Differential; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Immunocompromised Host; Immunohistochemistry; Kidney Transplantation; Leg Ulcer; Mucormycosis; Opportunistic Infections; Rhizopus; Transplantation Immunology; Treatment Outcome

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare fulminant opportunistic fungal infection that despite relevant treatment has high mortality. We present a case of a 3-year-old girl with acute lymphoblastic leukemia and ROCM, who was treated successfully with excessive surgery, systemic antifungal treatment with amphotericin B (AmB), posaconazole, and terbinafine as well as hyperbaric oxygen. Surgery included, beside extracranial and intracranial removal of infected areas, endoscopic sinus and skull base surgery with local AmB installation and in addition placement of an Ommaya reservoir for 114 intrathecal administrations of AmB. In addition, we review the literature of ROCM in pediatric patients with hematological diseases.

Topics: Amphotericin B; Antifungal Agents; Brain; Child, Preschool; Female; Humans; Hyperbaric Oxygenation; Mucormycosis; Naphthalenes; Nose; Opportunistic Infections; Orbit; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Terbinafine; Triazoles

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

Aspergillus flavus is the second leading cause of invasive and non-invasive aspergillosis, as well as the most common cause of fungal sinusitis, cutaneous infections, and endophthalmitis in tropical countries. Since resistance to antifungal agents has been observed in patients, susceptibility testing is helpful in defining the activity spectrum of antifungals and determining the appropriate drug for treatment. A collection of 199 clinical and environmental strains of Aspergillus flavus consisted of clinical (n=171) and environmental (n=28) were verified by DNA sequencing of the partial b-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MEC of caspofungin were determined in accordance with the Clinical and Laboratory Standards Institute M38-A2 document. Caspofungin, followed by posaconazole, exhibited the lowest minimum inhibitory concentrations (MIC). All isolates had caspofungin MEC90 (0.063μg/ml) lower than the epidemiologic cutoff values, and 3.5% of the isolates had amphotericin B MIC higher than the epidemiologic cutoff values. However, their clinical effectiveness in the treatment of A. flavus infection remains to be determined.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Caspofungin; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Echinocandins; Environmental Microbiology; Humans; Iran; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Opportunistic Infections; Triazoles; Voriconazole

We report a case of mycotic keratitis caused by Bipolaris oryzae with predisposing trauma from a foreign body. The fungus was identified by sequencing the internal transcribed spacer region, translation elongation factor 1α (TEF1) gene, and partial glyceraldehyde-3-phosphate dehydrogenase (GPDH) gene, and the species identity was confirmed on the basis of its characteristic conidial phenotype. The patient was treated with surgical intervention and antifungal agents, including intravenous fluconazole (FLC), oral itraconazole, topical 0.15% amphotericin B eye drops, and 0.5% FLC eye drops. To our knowledge, this is the first report of mycotic keratitis caused by B. oryzae worldwide.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Genes, Fungal; Humans; Keratitis; Male; Middle Aged; Ophthalmic Solutions; Opportunistic Infections; Phylogeny; Treatment Outcome

Investigations of both virulence factors and antifungal susceptibility profiles are crucial for understanding the pathogenesis and prognosis of ophthalmic mycoses. In this study, we investigated the in vitro antifungal susceptibility of amphotericin B (AMB), voriconazole (VRC), and natamycin (NAT) against a set of 50 fungal isolates obtained from patients with ocular mycoses using the Clinical and Laboratory Standards Institute broth microdilution method. In addition, putative virulence factor, such as secretory phospholipases and proteinases, and biofilm formation activity were analyzed. The geometric means (GMs) of the minimum inhibitory concentrations (MICs) of the antifungals across all isolates were the following (in increasing order): VRC (0.70 μg/mL), AMB (0.81 μg/mL), and NAT (1.05 μg/mL). The highest activity against 14 Aspergillus strains was exhibited by VRC (GM MIC: 0.10 μg/mL), followed by AMB and NAT (GM MICs: 0.21 and 0.27 μg/mL), respectively. However, for 12 Fusarium spp., the GM MIC of VRC (2.66) was higher than those of NAT and AMB (GM MICs 1.3 and 0.8 μg/mL, respectively). Proteinase and phospholipase activity were observed in 30 % and 42 % of the isolates, respectively, whereas only 8 % of the isolates were able to produce biofilms. Phospholipase activity was observed in all Fusarium isolates, but not in any of the Aspergillus isolates. In contrast, biofilm-forming capability was detected in 25 % of the Fusarium isolates, but none of the Aspergillus isolates. The differences in the MICs of AMB, VRC, and NAT, biofilm-forming ability and proteinase and phospholipase activities among the isolates were not significant (p > 0.05). Overall, our study suggests no significant correlation between the antifungal susceptibility profiles and virulence attributes of ocular fungal isolates.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Drug Resistance, Fungal; Eye Diseases; Fungi; Humans; Microbial Sensitivity Tests; Mycoses; Natamycin; Opportunistic Infections; Peptide Hydrolases; Phospholipases; Virulence; Virulence Factors; Voriconazole

Mucormycosis is a kind of rare opportunistic fungal disease and the incidence of which has gradually increased. Disseminated mucormycosis (DM) is a life-threatening infection that mostly occurs in immunocompromised patients. The lung and brain are usually involved in disseminated mucormycosis, and other sites are scare. We report the first case of disseminated mucormycosis whose infection sites included lung, skin, liver, vertebra, and spinal cord that ensued after a right lung pneumonectomy in an immunocompetent patient.. A 20-year-old female underwent a right lung pneumonectomy for "lung cancer" presented with an intermittent fever for two years. A computed tomography (CT) scan showed an enclosed outstanding mass in the right chest wall. The patient also suffered from lower limb numbness and weakness, difficulty walking, and dysuria. Medical examination showed superficial feeling of the abdominal wall was decreased from the T7 and T8 level; muscle strength for both lower limbs was decreased; muscle tension of both lower limbs was also diminished. A biopsy through the right chest wall mass and thoracic mass by fistula of chest wall showed broad nonseptate hyphae with right-angle branching, consistent with mucormycosis. With titration of amphotericin B and its lipid complex, the patient recovered.. Our case showed an unusual clinical presentation of disseminated mucormycosisin an immunocompetent patient.

Topics: Amphotericin B; Antifungal Agents; Bone and Bones; Female; Humans; Immunocompetence; Liver; Lung; Mucormycosis; Opportunistic Infections; Pneumonectomy; Skin; Spinal Cord; Tomography, X-Ray Computed; Young Adult

Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a rare invasive fungal agent that may lead to mortal clinical course in patients with hematological malignancies. This agent can be colonized in skin, lungs and intestines, and it can cause major opportunistic infections. Invasive systemic infections due to S.capitata have been reported in immunosuppressed patients. In this report, two patients with invasive S.capitata infections detected during the course of persistent neutropenic fever in acute leukemia, were presented. In both cases empirical caspofungin was added to the treatment, as no response was obtained by board-spectrum antibacterial therapy in neutropenic fever. In the first patient, there were no significant findings except the chronic inflammation observed in the biopsies which was performed for the symptoms of lymphadenitis, myositis, and hepatosplenic candidiasis. While persistent fever was on going, S.capitata was isolated from the blood and catheter cultures. There was no response after catheter removing and the introduction of amphotericin B and voriconazole therapy, therefore allogeneic stem cell transplantation plan for the second time for bone marrow aplasia was taken an earlier time. However, the patient died due to progressive pericardial and pleural effusion and multiorgan failure, although an afebrile process after stem cell transplantation could be obtained. Similarly the second patient had persistent fever despite empirical caspofungin treatment. The additional symptoms of diarrhea, abdominal pain and subileus have indicated an intraabdominal infection. During the follow up, S.capitata was isolated from the blood and catheter cultures. Catheter was removed and amphotericin B was initiated. No response was obtained, and voriconazole was added to treatment. Despite of an afebrile and culture-negative period, the patient died as a result of Acinetobacter sepsis and multiorgan failure. Minimal inhibitory concentration values for both of the Saprochete strains were found as 0.25 µg/ml for amfoterisin B, 1 µg/ml for flukonazol, 0.125 µg/ml for vorikonazol and 0.25 µg/ml for itrakonazol. Virulence model was created by injecting the isolates to the Galleria mellonella larvae, and the life cycle of the larvae were determined. The observation revealed that the infected larvae began to die on the second day and there was no live larvae remained on the eleventh day. In conclusion, S.capitata sho

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Caspofungin; Catheter-Related Infections; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Leukemia; Lipopeptides; Moths; Mycoses; Opportunistic Infections; Saccharomycetales; Voriconazole; Young Adult

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Cardiomyopathies; Electrocardiography; Heart Block; Humans; Male; Middle Aged; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Triazoles

Phaeohyphomycosis is a heterogeneous group of opportunistic infections caused by dematiaceous molds, which are distributed worldwide as plant pathogens but rarely cause human diseases. However, due to the growing populations of immunocompromised patients, these fungi are frequently recognized as important human pathogens. We are reporting this very rare, unique case for the first time from Islamabad, Pakistan, describing the association of visceral Phaeohyphomycosis caused by the opportunistic fungus Alternaria alternata, affecting the left kidney, with the immunocompromised state in a young incidentally detected patient with insulin-dependent type I diabetes. The case was diagnosed on the basis of a high index of clinical suspicion, microbial cultures, microscopy, imaging studies and endourological procedures. The patient did not respond well to the highly sensitive Amphotericin B, resulting in loss of the kidney. Therefore, we suggest that clinicians involved in treating immunocompromised patients should have a high degree of clinical suspicion for such opportunistic pathogens to allow timely initiation of the correct diagnostic and therapeutic work-up.

Topics: Alternaria; Amphotericin B; Antifungal Agents; Diabetes Mellitus, Type 1; Humans; Hydronephrosis; Hypoglycemic Agents; Immunocompromised Host; Insulin; Male; Nephrectomy; Opportunistic Infections; Phaeohyphomycosis; Predictive Value of Tests; Risk Factors; Treatment Outcome; Urinary Tract Infections; Young Adult

To our knowledge, these are the first reports of bloodstream infections by Trichosporon inkin in patients with pemphigus.. Trichosporon inkin, a novel organism causing bloodstream infection, was detected in 2 patients with pemphigus. An elderly man with pemphigus foliaceus died despite treatment with liposomal amphotericin B, 3 mg/kg/d, and a young girl with pemphigus vulgaris responded to treatment with voriconazole, 8 mg/kg/d, for 24 days. One of the T inkin isolates had a minimal inhibitory concentration of 2 mg/L against amphotericin B, suggesting resistance to the drug.. Delayed suspicion of invasive infection by T inkin may result in a poor outcome in patients with severe forms of pemphigus. This opportunistic infection is highly refractory to conventional potent antifungal treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Child; Drug Resistance, Fungal; Fatal Outcome; Female; Humans; Male; Microbial Sensitivity Tests; Opportunistic Infections; Pemphigus; Severity of Illness Index; Trichosporon; Trichosporonosis; Voriconazole

During a research project on fungal Candida species in patients wearing obturator treated with radiotherapy for their recurrent nasopharyngeal carcinoma, we serendipitously observed the presence of black fungus in two consecutive samples from a patient.. The samples were collected from a 57 year-old Hong Kong gentleman who diagnosed to have undifferentiated type of nasopharyngeal carcinoma. He was treated with definitive concurrent chemoradiotherapy followed by adjuvant chemotherapy and then received a second-course radiotherapy with IMRT. 18S rDNA sequencing revealed that the isolates belong to Exophiala dermatitidis which was susceptible to fluconazole, itraconazole, ketoconazole and voriconazole. Interestingly, E. dermatitidis isolates were resistant to caspofungin and one isolate was resistant to amphotericin B. Both isolates formed biofilms comparable to that of Candida albicans. Single isolate of E. dermatitidis showed hemolysin and proteinase ability comparable to C. albicans whilst the other isolate was not.. We, for the first time, reported the discovery of a black fungus-E. dermatitidis isolates derived from a patient with nasopharyngeal carcinoma treated with radiotherapy. These isolates were shown to be resistant to caspofungin, a major antifungal agent for systemic candidiasis. As little is known about the black fungus in the clinical setting, it is important that clinicians must keep abreast of the new discovery in this field.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Carcinoma; Caspofungin; Chemoradiotherapy; Chemotherapy, Adjuvant; Drug Resistance, Fungal; Echinocandins; Exophiala; Fluconazole; Humans; Immunocompromised Host; Itraconazole; Ketoconazole; Lipopeptides; Male; Middle Aged; Mouth Diseases; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Opportunistic Infections; Phaeohyphomycosis; Radiotherapy, Intensity-Modulated; Voriconazole

Trichosporon asahii is a basidiomycete yeast responsible for white piedra and onychomycosis in the immunocompetent host. In the immunocompromised patients, invasive infections are reported; their diagnosis is difficult and they are associated with high mortality rate. Urinary infection due to Trichosporon Asahi is rare but its incidence increasing. We report the case of a 58 year old diabetic patient. The yeast was isolated from urine samples of three consecutive crops in pure form. The patient improved after antifungal therapy.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Diabetes Mellitus, Type 1; Humans; Immunocompromised Host; Male; Middle Aged; Opportunistic Infections; Trichosporon; Trichosporonosis; Urinary Tract Infections; Urine; Virulence

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue.. Hemofagositik lenfohistiositoz (HLH) uzamış ateş, sitopeni, hepatosplenomegali semptomları ile seyreden, active olmuş, morfolojik olarak benign makrofaj ve doğal öldürücü hücreler ile sitotosik T lenfosit fonksiyon bozukluğu sonucu gelişen hiperenflamatuvar bir durumdur. İki aylık düşmeyen ateş yakınması ile başvuran hasta HLH tanısı aldı ve hastanın genetik incelemesinde UNC13D (c.175G>C; p.Ala59Pro) geninde yeni tanımlanan bir mutasyon saptandı. Hastaya deksamatazon, etopozit ve intratekal metotreksat tedavileri başlandı. Tedavinin 2. haftasında, üç doz etopozit aldıktan sonra, yumuşak damakta plak lezyonu fark edildi ve bu nekrotik lezyon debride edildi. Debridman materyalinin patolojik incelemesinin PAS, Grocott boyamasında aspergilloz enfeksiyonu ile uyumlu olarak çok sayıda septalı hif görüldü. Etopozid tedavisi sonlandırılarak altı hafta boyunca amphotericin B tedavisi verildi. HLH 2004 tedavi protokolü oral siklosporin ile sekiz haftaya tamamlandı. HLH tedavisi sırasında yumuşak damak perforasyonuna neden olacak kadar ağır aspergilloz enfeksiyonu geçiren bir olgu bildirilmemiştir. İmmünyetmezlikli hastada mantar enfeksiyonları nazal septum perforasyonuna neden olabilmektedir ve tedavi nekrotik dokunun debridmanı ve antifungal tedavi ile sağlanabilmektedir.

Topics: Amino Acid Substitution; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Combined Modality Therapy; Cyclosporine; Debridement; Dexamethasone; Drug Therapy, Combination; Etoposide; Female; Humans; Immunocompromised Host; Infant; Lymphohistiocytosis, Hemophagocytic; Membrane Proteins; Methotrexate; Mutation, Missense; Nasal Septal Perforation; Opportunistic Infections; Palate, Soft; Point Mutation; Stomatitis

We describe the first case of a psoas muscle abscess caused by Nocardia beijingensis and subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum in a renal transplant recipient. The patient was treated for nocardiosis with percutaneous drainage and intravenous trimethoprim/sulfamethoxazole (TMP/SMX) combined with imipenem for 2 weeks, followed by a 4-week course of intravenous TMP/SMX and then oral TMP/SMX. During hospitalization for the psoas muscle abscess the patient developed cellulitis with subcutaneous nodules of his right leg. Skin biopsy and cultures revealed a dematiaceous mold, subsequently identified as P. parasiticum by DNA sequencing. The subcutaneous phaeohyphomycosis was treated with surgical drainage and liposomal amphotericin B for 4 weeks followed by a combination of itraconazole and terbinafine. The patient gradually improved and was discharged home after 18 weeks of hospitalization.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Drainage; Graft Rejection; Humans; Immunosuppressive Agents; Itraconazole; Kidney Transplantation; Male; Middle Aged; Nocardia; Nocardia Infections; Opportunistic Infections; Phaeohyphomycosis; Psoas Abscess; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

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

Opportunistic infections cause a significant morbidity and mortality in immunocompromised patients. We describe the case of a patient with skin fusariosis and a probable cerebral toxoplasmosis after UCB stem cell transplantation for B-cell acute lymphoblastic leukaemia. Fusarium species (spp) infections are difficult to treat. To date, there has been no consensus on the treatment of fusariosis and the management of its side effects. Given the negative pretransplant Toxoplasma serology in this case, identifying the origin of the Toxoplasma infection was challenging. All usual transmission routes were screened for and ruled out. The patient's positive outcome was not consistent with that of the literature reporting 60% mortality due to each infection.

Topics: Adolescent; Amphotericin B; Cord Blood Stem Cell Transplantation; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Febrile Neutropenia; Female; Fusariosis; Gibberella; Humans; Mycophenolic Acid; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimethamine; Retreatment; Sulfadiazine; Toxoplasmosis, Cerebral

Signo del cornete negro en un caso de mucormicosis rinocerebral.

Topics: Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cavernous Sinus Thrombosis; Combined Modality Therapy; Cranial Nerve Diseases; Dexamethasone; Diagnosis, Differential; Disease Progression; Encephalitis; Ethmoid Sinusitis; Fatal Outcome; Humans; Interferons; Magnetic Resonance Imaging; Male; Maxillary Sinusitis; Melanoma; Mucormycosis; Opportunistic Infections; Rhizopus; Spinal Neoplasms; Tomography, X-Ray Computed; Turbinates

Dematiaceous, or dark-pigmented, fungi are known to cause infections such as phaeohyphomycosis, chromoblastomycosis, and mycetoma. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We present a retrospective chart review of 27 SOTR who developed phaeohyphomycosis infections post transplant from 1988 to 2009.. Cases were reviewed for fungal species isolated, date and source of culture, immunosuppressive and fungal therapy used, and outcome. The majority of isolates obtained were from the skin and soft tissue, with 3 pulmonary and brain abscesses.. The time from transplantation to onset of infection ranged from 2 months to 11 years. The species isolated were Exophiala (11), Ochroconis (3), Alternaria (2), Phoma (2), Wangiella (1), Cladosporium (1), Aureobasidium (1), Chaetomium (1), Coniothyrium (1), and non-sporulating fungi (2). An additional 4 patients had infections confirmed by pathology, but no cultures were done. Most of the affected skin lesions were surgically debrided and treated with itraconazole; 2 patients were treated with voriconazole and 2 with amphotericin D. Death from fungal disease occurred only in patients with pulmonary and brain abscesses.. As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Brain Abscess; Debridement; Female; Humans; Immunosuppression Therapy; Itraconazole; Lung Abscess; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Phaeohyphomycosis; Retrospective Studies; Time Factors; Voriconazole; Young Adult

Mucormycosis are rare fungal infections occurring chiefly in the lung or the rhinocerebral compartment, particularly in patients with immunodeficiency or mellitus diabetes. We report the case of an elderly patient with cutaneous mucormycosis caused by Rhizopus microsporus.. An 89-year-old man presented a skin lesion of the forearm rapidly becoming inflammatory and necrotic. The patient had been treated for 2months with oral corticosteroids for idiopathic thrombocytopenia. Histological and mycological examination of the skin biopsy revealed the presence of a filamentous fungus, R. microsporus. The outcome was unfavorable, despite prescription of high-dose liposomal amphotericin B.. Mucormycosis are infrequent opportunistic infections caused by angio-invasive fungi belonging to the Mucorales order. Cutaneous presentations are rare, and in rare cases the species R. microsporus is isolated in clinical samples. Diagnosis is based on histological examination highlighting the characteristic mycelium within infected tissue, together with ex vivo mycological identification using morphological and molecular methods. Treatment consists of liposomal amphotericin B combined with debridement surgery.. R. microsporus is a marginal fungal species rarely isolated in clinical practice, and even less in dermatology departments. This clinical case report highlights the severity of infection with this fungus, particularly in the absence of early surgery.

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Amphotericin B; Biopsy; Dermatomycoses; Dose-Response Relationship, Drug; Humans; Male; Mucormycosis; Necrosis; Opportunistic Infections; Palliative Care; Rhizopus; Skin; Thrombocytopenia

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

Zygomycosis is an opportunistic infection generally found in immunocompromised individuals. Herein we present a pediatric patient with primary cutaneous mucormycosis that developed at a site of trauma. Diagnosis and treatment are discussed.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Catheters, Indwelling; Child; Dermis; Female; Humans; Immunocompromised Host; Lymphohistiocytosis, Hemophagocytic; Myelodysplastic Syndromes; Opportunistic Infections; Remission Induction; Zygomycosis

Topics: Amphotericin B; Antifungal Agents; Humans; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Triazoles

Topics: Abdominal Wall; Acute Kidney Injury; Adult; Amphotericin B; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Clostridium Infections; Cytomegalovirus Infections; Debridement; Dermatomycoses; Hepatitis; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Mucormycosis; Opportunistic Infections; Postoperative Complications; Primary Graft Dysfunction; Reoperation; Triazoles

Mucormycosis are the fungal infections caused by emerging ubiquitous filamentous fungi classified as zygometes and order as mucorales. They occur mainly in immunosuppressed patients and diabetics. The onset of hemoptysis, in this context, may rapidly become life-threatening.. We report the case of a man of 83 years, Caribbean with a history of non-insulindependent diabetes and HTLV1 seropositive. At admission he presented with fever, cough and cachexia. Chest X-ray revealed a snapshot of excavation within alveolar consolidation. Endoscopy showed a mucopurulent plug obstructing lingula. The histological appearance of bronchial biopsies was in favor of mucormycosis. A combined treatment with liposomal amphotericin B and posaconasole was implemented, but the occurrence of abundant hemoptysis led us to make a left upper lobectomy. Finally, the outcome was favorable and the patient was discharged after hospitalization of 56 days.. A medicosurgical treatment during mucormycosis complicating bronchopulmonary hemoptysis not controlled by medical treatment alone seems to offer an effective therapeutic strategy.

Topics: Aged, 80 and over; Amphotericin B; Combined Modality Therapy; Diabetes Mellitus, Type 2; Hemoptysis; Humans; Lung Diseases, Fungal; Male; Mucormycosis; Opportunistic Infections; Pneumonectomy; Triazoles

Topics: Abdominal Pain; Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Anti-HIV Agents; Histoplasma; Histoplasmosis; Humans; Ileal Diseases; Ileocecal Valve; Infusions, Intravenous; Intestinal Fistula; Itraconazole; Male; Opportunistic Infections; Rare Diseases; Risk Assessment; Treatment Outcome

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

Yeasts occur as part of the normal human microbiota. Nevertheless, some species are opportunistic, affecting immunocompromised patients such as those undergoing oncologic treatment.. To detect the presence of yeasts in patients suffering from head and neck cancer who are receiving radiation therapy and display lesions in the oral cavity, compatible with candidiasis; and to evaluate the antifungal susceptibility of the isolates recovered.. Sixty samples from patients were obtained by swabbing the oral mucosa. Identification of isolates were performed by classical taxonomic, morphological and biochemical methods as well as by using commercial identification kits. Susceptibility to antifungal drugs was determined by the agar diffusion method with Neosensitabs(®) disks.. Forty-six samples (77%) yielded positive findings, and species recovered were: Candida albicans (22 isolates), Candida tropicalis (13 isolates), Candida parapsilosis (six strains), Candida krusei (three strains), Candida dubliniensis and Saccharomyces cerevisiae (one each). All strains were susceptible to itraconazole, clotrimazole, voriconazole, nystatin and amphotericin B. On the other hand, 65% of strains were miconazole-susceptible while 35%, showed intermediate susceptibility. With regard to ketoconazole, only three strains (7%) corresponding to C. albicans (one isolate) and C. krusei (two isolates) displayed intermediate susceptibility. Only C. krusei strains were resistant to fluconazole while all the other species were susceptible. Eventually, only six isolates (13%) were susceptible to terbinafine while the remaining strains were resistant in vitro.. Early detection of etiological agents causing lesions, as well as the evaluation of their susceptibility to commonly used drugs, are crucial in order to choose the appropriate treatment that will minimize complications while improving the quality of patients' lives.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Oral; Drug Resistance, Fungal; Head and Neck Neoplasms; Humans; Microbial Sensitivity Tests; Mycoses; Naphthalenes; Nystatin; Opportunistic Infections; Saccharomyces cerevisiae; Species Specificity; Terbinafine; Triazoles

Non-Hodgkin's lymphoma (NHL) is predominantly a disease of lymph nodes, but extranodal involvement is not very uncommon. Palatal involvement by NHL is rare. Mucormycosis is a devastating fungal infection commonly seen in immunocompromised individuals, including those with NHL, but it is affecting the same region has been reported very rarely. Simultaneous infiltration of hard palate by NHL and mucormycosis is extremely unusual. Herein we describe a patient who presented with palatal hole with histopathological examination revealing presence of lymphoma with colesional mucormycosis. The identification of mucor was vital because chemotherapy alone in the absence of antifungals would have had devastating consequences as the mortality of untreated mucormycosis is high.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Debridement; Doxorubicin; Humans; Lymphoma, T-Cell; Male; Middle Aged; Mucormycosis; Nasal Cavity; Opportunistic Infections; Palatal Neoplasms; Palate, Hard; Prednisolone; Rhinitis; Vincristine

Mucormycosis is a rapidly progressive fungal infection that usually occurs in patients with diabetes mellitus or in immunocompromised patients. Sinus involvement is the most common clinical presentation and the rates of mortality increase with the orbital extension. The treatment of mucormycosis includes aggressive surgical debridement and systemic antifungal therapy. Early diagnosis and prompt initiation of effective antifungal drugs are essential for successful outcome. However, the role of orbital exenteration for the case of orbital involvement remains controversial, and the drugs effective against mucormycosis are limited. We present a successfully treated case with rhino-orbital mucormycosis caused by Rhizopus oryzae in a diabetic and dialysis patient. The early diagnosis, surgical debridement and a new combination therapy with liposomal amphotericin B and micafungin were effective. This new combination antifungal therapy will be useful for the treatment of mucormycosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Drug Therapy, Combination; Echinocandins; Endoscopy; Humans; Lipopeptides; Magnetic Resonance Imaging; Male; Maxillary Sinus; Maxillary Sinusitis; Micafungin; Necrosis; Opportunistic Infections; Orbital Diseases; Rhinitis; Rhizopus; Tomography, X-Ray Computed; Turbinates

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Brain Diseases; Central Nervous System Fungal Infections; Combined Modality Therapy; Debridement; Diabetes Complications; Early Diagnosis; Endoscopy; Fatal Outcome; Female; Humans; Male; Maxillary Sinus; Middle Aged; Mucormycosis; Nose Diseases; Opportunistic Infections; Oroantral Fistula; Paranasal Sinus Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Pregnancy Complications, Infectious; Sinusitis; Zygomycosis

Topics: Alemtuzumab; Amphotericin B; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiprotozoal Agents; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Opportunistic Infections; Treatment Outcome

Rhinocerebral mucormycosis (RCM) is a rare, fulminating opportunistic fungal infection caused by a fungus of order Mucorales. These fungi are ubiquitus, subsisting on decaying vegetation and diverse organic material. Although fungi and spores of Mucorales show minimal intrinsic pathogenicity towards normal person, they can initiate aggressive and fulminating infection in immunocompromised host. Since RCM occurs infrequently, it may pose a diagnostic and therapeutic dilemma for those who are not familiar with its clinical presentation.. We present a patient with classical presentation of RCM involving paranasal sinuses, orbit, and cranial base who was treated by combination of aggressive surgical and medical therapy.. The purpose of this paper is to draw attention to the clinical presentation and pathogenesis of RCM and to emphasize need for high index of suspicion in diagnosis and treatment.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Debridement; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fatal Outcome; Female; Humans; Infusions, Intravenous; Lip Diseases; Maxilla; Middle Aged; Mouth Diseases; Mucormycosis; Nose; Nose Diseases; Opportunistic Infections; Orbital Diseases; Paranasal Sinus Diseases; Tomography, X-Ray Computed

Cryptococcosis is a significant opportunistic mycoses in organ transplant recipients. Topical developments in the field in the past few years have highlighted important issues and at the same time raised new questions regarding the management of this yeast. These include, for example, management of pretransplant cryptococcosis during transplant candidacy and timing of transplant in these instances; potential for donor transmission of cryptococcosis in light of recent fatal transmissions; and prevention and treatment of Cryptococcus-associated immune reconstitution syndrome. Discussed herein are challenges posed by these issues and evidence-based data to optimize the management of posttransplant cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Calcineurin Inhibitors; Cryptococcosis; Evidence-Based Medicine; Humans; Immune Reconstitution Inflammatory Syndrome; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Prevalence; Risk Factors; Transplantation

S. dimidiatum (recently reclassified as N. dimidiatum) is a fungus that causes nail and/or superficial skin infection. It may also cause subcutaneous and deep infection, chiefly in immunocompromised patients.. An 87-year-old male treated with oral corticosteroids for sarcoidosis consulted for violaceous cutaneous nodules on the back of his hands. Histopathological examination revealed epithelioid cell granulomas with numerous mycelial filaments and multiple spores. Culture of a biopsy sample resulted in growth of numerous colonies of S. dimidiatum and the patient was treated with intravenous amphotericin B.. This organism is transmitted by direct or indirect contact with contaminated soil or plants. It mainly causes superficial skin and nail infections, and may result in deeper infections on rare occasions. We report a case of subcutaneous infection with S. dimidiatum in an immunocompromised patient (due to general steroid therapy) that was successfully treated using amphotericin B.

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Amphotericin B; Antifungal Agents; Biopsy; Coelomomyces; Dermatomycoses; Diagnosis, Differential; Hand Dermatoses; Humans; Infusions, Intravenous; Male; Opportunistic Infections; Sarcoidosis; Skin

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cellulitis; Cranial Nerve Diseases; Delayed Diagnosis; Diabetes Complications; Disease Progression; Disease Susceptibility; Encephalitis; Fatal Outcome; Female; Fungemia; Humans; Male; Middle Aged; Mucormycosis; Multiple Organ Failure; Opportunistic Infections; Sinusitis; Vision Disorders

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

Topics: Accidental Falls; Accidents, Traffic; Aged, 80 and over; Amphotericin B; Amputation, Surgical; Antifungal Agents; Combined Modality Therapy; Debridement; Fatal Outcome; Female; Fractures, Bone; Fractures, Open; Fungemia; Humans; Humeral Fractures; Immunocompetence; Lacerations; Middle Aged; Mucormycosis; Multiple Trauma; Opportunistic Infections; Postoperative Complications; Recovery Room; Splenectomy; Splenic Rupture; Thigh; Transfusion Reaction; Wound Infection

Mucormycosis of the gastrointestinal tract is a rare infection that usually occurs in patients who are immunocompromised and carries a high mortality. We report four cases of gastrointestinal mucormycosis seen over a one year period with different presentations, risk factors and different anatomical sites of involvement. A preoperative diagnosis was made only in one patient. All underwent surgery, three survived and one died postoperatively from multiorgan failure.

Topics: Adult; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Fatal Outcome; Gastrointestinal Diseases; Humans; Infant; Male; Mucormycosis; Multiple Organ Failure; Opportunistic Infections; Risk Factors; Tomography, X-Ray Computed; Young Adult

This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillus nidulans; Cryptococcus neoformans; Female; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Neuroaspergillosis; Opportunistic Infections; Pregnancy; Pregnancy Complications, Infectious; Rare Diseases; Treatment Outcome; Voriconazole

Two German Shepherd dogs with sequential opportunistic infections are described. The first was a 2-year-old male with cryptococcal rhinitis that spread to involve the optic nerves and brain. It was successfully treated with combination therapy utilising amphotericin B administered for 2 years, but the dog developed a disseminated Aspergillus deflectus infection 5 years later and was euthanased. The second case was a 4-year-old male that presented for a severe, deep-seated infection of the right antebrachium, with gradual extension to contiguous tissues. Neosartorya fischeri (anamorph; Aspergillus fischerianus) was isolated in pure culture and detected in histological sections. The infection was refractory to itraconazole, but resolved after amputation of the affected limb. Five months later, the dog developed a localised cutaneous lesion on the proximal pelvic limb, from which Pythium insidiosum was isolated and then visualised in tissue sections, together with a structure thought to be grass seed. This lesion was treated by wide surgical resection, although it was reported that the dog died of disseminated disease some months later. These cases provide further circumstantial evidence that young adult German Shepherd dogs have a predilection to developing invasive infections with fungi and other saprophytic pathogens.

Topics: Amphotericin B; Animals; Antifungal Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Fatal Outcome; Itraconazole; Male; Mycoses; Opportunistic Infections

Immunosuppressive agents increase the vulnerability of solid organ transplant patients to opportunistic infections. An atypical clinical presentation of a bacterial and fungal co-infection makes diagnosis and treatment even more challenging in this population. A 54-year-old hypertensive woman underwent a cadaveric kidney transplant after years on hemodialysis. Her treatment included mycophenolate, tacrolimus, and prednisone. By post-transplant week 8, she had pneumonia followed by progressive visual changes and seizures. Diagnostic work-up, consisting of magnetic resonance imaging of the brain and chest x-ray, showed several cerebral ring-enhancing lesions, and a pulmonary cavitary lesion. Disseminated nocardiosis was suspected and therapy was started. Skin biopsy was taken from a nodular lesion and culture confirmed Nocardia species infection. During hospitalization, neurological deficit persisted with worsening of brain lesions. She underwent excision of a brain abscess and the final pathologic report showed mucormycosis, revealing the patient's co-infection by 2 different pathogens. After therapy with liposomal amphotericin B and posaconazole, she has remained stable for more than 1 year. Disseminated nocardiosis masked and delayed the diagnosis and treatment of a more aggressive and worrisome organism. Mucormycosis, as a non-fatal isolated brain abscess without rhinal involvement, is an atypical presentation, and only a few cases have been reported.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Coinfection; Female; Humans; Kidney Transplantation; Middle Aged; Nocardia; Nocardia Infections; Opportunistic Infections; Pneumonia, Bacterial; Radiography; Triazoles; Zygomycosis

Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation.

Topics: Adult; Amphotericin B; Antibodies, Monoclonal, Murine-Derived; Antiprotozoal Agents; Antiviral Agents; Epstein-Barr Virus Infections; Ganciclovir; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leishmaniasis, Visceral; Lymphoproliferative Disorders; Male; Meglumine; Meglumine Antimoniate; Opportunistic Infections; Organometallic Compounds; Postoperative Complications; Remission Induction; Rituximab; Sirolimus

Intensified chemotherapy and hematopoietic stem cell transplantation result in severe and prolonged granulocytopenia with an increased risk of invasive fungal infections. The major fungal species that cause serious infections in cancer patients are Candida species and Aspergillus species. The main features of Candida infection in this context are oropharyngeal candidiasis and Candida esophagitis, chronic disseminated candidiasis, also known as hepatosplenic candidiasis, and candidemia. Aspergillus can cause severe lung infection but also sinusal or CNS infection. Because invasive fungal infections are severe and often life-threatening, preventive and empirical managements have become standard practice. An increasing number of antifungal drugs is now available, notably lipid formulations of amphotericin B (liposomal amphotericin B), new azoles with broad spectrum of activity and echinocandin.

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Azoles; Candidiasis; Child; Cryptococcosis; Echinocandins; Humans; Mycoses; Neoplasms; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Treatment Outcome

Topics: Amphotericin B; Biopsy, Needle; Follow-Up Studies; Foot Dermatoses; Fungemia; Fusarium; Humans; Immunocompromised Host; Immunohistochemistry; Leukemia, Myeloid; Magnetic Resonance Imaging; Male; Middle Aged; Muscular Diseases; Mycoses; Opportunistic Infections; Risk Assessment; Severity of Illness Index; Toes; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Biopsy; Debridement; Fatal Outcome; Female; Hemochromatosis; Hepatic Encephalopathy; Humans; Intubation, Gastrointestinal; Liver; Liver Failure, Acute; Middle Aged; Mucormycosis; Necrosis; Nose; Nose Diseases; Opportunistic Infections; Triazoles

A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress.

Topics: Animals; Antifungal Agents; Base Sequence; Calcineurin; Candida glabrata; Candidiasis; DNA Primers; DNA, Fungal; Drug Resistance, Fungal; Female; Fungal Proteins; Genes, Fungal; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mutation; Opportunistic Infections; Transcription Factors; Virulence

Mucormycosis are opportunistic infections mostly observed in immunocompromised patients. We report the case of a 13-year-old girl who suffered a systemic mucormycosis without presenting the usual risk factors. She was undergoing antineoplastic chemotherapy for advanced osteosarcoma of the femur with an uncommunicative pathologic fracture and pulmonary metastasis. Absidia corymbifera was isolated from skin lesions at the primary tumor site. She subsequently developed fungal pulmonary localizations and blood vessel thrombosis. Surgical treatment together with systemic, high doses of liposomal amphotericin B, posaconazole, and caspofungin cured the local infection and controlled systemic lesions. Unfortunately, the break in chemotherapy led to pulmonary metastasis progression.

Topics: Absidia; Adolescent; Amphotericin B; Antineoplastic Agents; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Femoral Neoplasms; Humans; Lipopeptides; Mucormycosis; Opportunistic Infections; Osteosarcoma; Triazoles

Protothecosis is an uncommon human infection caused by Prototheca. Prototheca spp can be considered as saprophytes, and in spite of their frequency in the environment, they are of low virulence and may cause chronic infection with low-grade inflammation in humans. At present, only three species are recognized: Prototheca wickerhamii, Prototheca zopfii and Prototheca stagnora. Of these, the former two have been associated with human disease. This study was an investigation of the clinical and microbiological features of a case of granulomatous lymphadenitis due to P. zopfii var. portoricensis in an immunocompetent man in China.. We report the case of a 39-year-old male, who presented with swollen lymph nodes, from which the organism was isolated and identified by the RapidID Yeast Plus test (Remel, Santa Fe, NM, USA) and PCR molecular analysis. The pathogenicity of the isolate was confirmed in a mouse model and antifungal drug susceptibility testing was carried out.. The pathogen was identified as Prototheca zopfii. The DNA sequence of the 18S SSU rDNA regions of the isolate strain were 100% (1205/1205) identical with Prototheca zopfii var. portoricensis. Antifungal susceptibility tests revealed that it was sensitive to amphotericin B, but resistant to 5-flucytosine, fluconazole, ketoconazole, and itraconazole. The patient responded to treatment with intravenous itraconazole and amphotericin B.. Based on the patient's symptoms and microscopic evaluation, cultures, and molecular analyses of the isolate, granulomatous lymphadenitis due to P. zopfii var. portoricensis was diagnosed. P. zopfii var. portoricensis as a causative agent of human lymphadenitis in an immunocompetent case has not been reported, though a few cases of protothecosis have been reported in China. The real number of protothecosis cases may be greater than that reported in the literature. Thus, clinicians should be vigilant for any unknown cause of granulomatous lymphadenitis and should undertake an intensive histopathology, mycology examination, and even molecular analysis to rule out or confirm a potential Prototheca infection.

Topics: Adult; Amphotericin B; Animals; Anti-Infective Agents; Base Sequence; China; Disease Models, Animal; DNA Primers; Humans; Immunocompetence; Itraconazole; Lymphadenitis; Male; Mice; Microbial Sensitivity Tests; Opportunistic Infections; Prototheca

Renal allograft recipients are prone to opportunistic infections, rarely multiple coexisting infections, due to the immunocompromised state. To the best of our knowledge, no case of a co-existing polyoma virus nephropathy and pulmonary histoplasmosis in a renal allograft recipient has been reported so far in the available literature. A 55-year-old male renal allograft recipient underwent graft biopsy for asymptomatic graft dysfunction. The graft biopsy showed features of polyoma virus nephropathy. Soon after, he developed fever with pulmonary nodules. Fine-needle aspiration from lung nodules showed intracellular yeast forms of histoplasma. The patient responded well to amphotericin B with subsidence of fever. The co-existence of renal allograft-limited infection like polyoma virus and systemic fungal infection such as histoplasmosis should be kept in mind in a transplant recipient with graft dysfunction and non-specific systemic symptoms. Prompt recognition of these infections permits the clinician to institute appropriate therapeutic modification and improved survival.

Topics: Amphotericin B; Histoplasmosis; Humans; Kidney Transplantation; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Polyomavirus Infections

To present and discuss the case of a diabetic patient admitted with acidoketotic coma, with inner canthus tumefaction due to mucormycosis.. A 38-year-old diabetic man was admitted with acidoketotic coma and poor general health status. Clinical examination found right inner canthus tumefaction and mucopurulent rhinorrhea. Endoscopy of the nasal fossae found medial meatus sphaceluses. Sinus CT scan found a bilateral ethmoid infiltrating and osteolytic infectious process. Emergency endoscopic bilateral ethmoidectomy was performed. Mucormycosis was diagnosed, and liposomal amphotericin B was administered intravenously for 1 month then replaced by posaconazole. The patient was followed up monthly; the antifungal treatment was terminated after 8 months, the disease appearing to have resolved.. Mucormycosis is one of the most rapidly fatal fungal infections. Facial and cerebral CT scan is essential and is systematically abnormal in case of sinonasal mucormycosis. Emergency multidisciplinary treatment should address the diabetes and include rapid surgical debridement and effective antifungal medication. The reference antifungal is amphotericin B, to be administered at maximal dose (3 to 5 mg/kg per day). Posaconazole, available in Europe since July 2005, proved successful in the present case.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Diabetes Complications; Diabetic Ketoacidosis; Endoscopy; Ethmoid Sinusitis; Humans; Infusions, Intravenous; Male; Mucormycosis; Opportunistic Infections; Rhinitis; Tomography, X-Ray Computed; Triazoles

Lichtheimia corymbifera (syn. Absidia corymbifera, Mycocladus corymbifer) is an ubiquitous cosmopolitan mold that can cause primary cutaneous and deep tissue infection in healthy individuals. We report a subcutaneous L. corymbifera infection in a 13-year-old immune-competent child, with a severe traumatic injury, with a successful outcome after early diagnosis and treatment with lipid amphotericin B, early debridement, and vacuum-assisted closure (VAC).

Topics: Absidia; Accidents, Traffic; Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Combined Modality Therapy; Compartment Syndromes; Debridement; Early Diagnosis; Fractures, Bone; Humans; Immunocompetence; Leg Bones; Male; Mucormycosis; Multiple Trauma; Negative-Pressure Wound Therapy; Opportunistic Infections; Surgical Wound Infection; Wound Infection

Visceral leishmaniasis is a rare opportunistic infection in renal transplantation patients and its presentation may be associated with or masked by many other factors in immunosuppressed patients. So, if it is not searched for in particular, diagnosis may be easily overlooked or delayed in renal transplant patients. A 32-year-old renal transplant recipient devoleped splenomegaly, pyrexia and pancytopenia. Six months after the first bone marrow examination, the delayed diagnosis was made possible by a second bone marrow aspiration. Liposomal amphotericin B was effective in his treatment although he had a recurrence. Early diagnosis of visceral leishmaniasis is crucial for the renal transplant recipient's therapy; and even in treated patients, the mortality rate may be high. In our case, although the time up to diagnosis was as long as six months after the onset of symptoms, response to treatment was satisfactory with higher doses of liposomal amphotericin B in the second cycle. Also, in the short term, the rate of recurrence was comparable to other reported patients who were diagnosed and treated in a month.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Biopsy, Needle; Bone Marrow; Delayed Diagnosis; Humans; Immunocompromised Host; Kidney Transplantation; Leishmaniasis, Visceral; Liposomes; Male; Opportunistic Infections; Recurrence

The in vitro activity of isavuconazole was compared to those of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and ravuconazole against 300 clinical isolates of Pseudallescheria boydii, Paecilomyces lilacinus, Fusarium spp., Bipolaris spicifera, Curvularia lunata, Alternaria alternata, Exophiala spp., Rhizopus arrhizus, Mucor circillenoides, Absidia corymbifera, Blastomyces dermatitidis, Histoplasma capsulatum and Coccidioides posadasii. MICs were determined by a broth macrodilution method based on the CLSI M38-A procedure. The triazoles were relatively uniform in that they showed strong in vitro inhibitory activity against most of the tested fungi. In vitro activity was variable with strains of P. lilacinus while with Fusarium spp., the triazoles were found to have limited in vitro activity and amphotericin B was moderately active. The results suggest that isavuconazole is a broad-spectrum antifungal agent, effective against a wide range of moulds in vitro.

Topics: Amphotericin B; Antifungal Agents; Fungi; Humans; Microbial Sensitivity Tests; Mycoses; Nitriles; Opportunistic Infections; Pyridines; Triazoles

Topics: Adrenal Cortex Hormones; Amphotericin B; Animals; Communicable Diseases; Cyclosporine; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Immunosuppressive Agents; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Lymphohistiocytosis, Hemophagocytic; Macrophages; Middle Aged; Neoplasms; Opportunistic Infections; Pancytopenia; Polymerase Chain Reaction; Splenomegaly

Cryptococcosis is a disseminated fungal disease typically associated with immunosuppression and characterized by high mortality rates. Cryptococcus neoformans has been reported to be isolated from blood cultures in around 20% of patients with cryptococcosis, and cryptococcemia has been correlated with poor prognosis. We report a case of fatal C. neoformans fungemia in a neutropenic patient with a history of chronic lymphocytic leukemia treated with alemtuzumab. The patient presented with loss of consciousness and died after 5 days of antifungal therapy with liposomal amphotericin B. The international literature regarding opportunistic infections after immunosuppressive therapy with alemtuzumab with particular attention on fungal infections has also been reviewed.

Topics: Aged; Alemtuzumab; Amphotericin B; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antifungal Agents; Antineoplastic Agents; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Fungemia; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neutropenia; Opportunistic Infections

Mucormycosis is a rare fungal infection occurring most frequently in immunocompromised patients. The pathogens are filamentous fungi, order of Mucorales. Disseminated mucormycosis is a severe, life treating disease. Early diagnosis is a major determinant for prognosis, however, it remains difficult. The management consists in an early antifungal therapy using lipid formulation of amphotericin B associated with an extensive surgical debridement. Despite this therapeutic of choice, the mortality of disseminated mucormycosis remains high.. We report the case of disseminated mucormycosis in a 25 years old woman 9 months after a pulmonary transplantation. The clinical presentation included pulmonary and thyroid localization and the pathogen was Absidia corymbifera. The patient survived thanks to a large surgical debridement, and an early antifungal bitherapy by lipid formulation of amphotericin B and posaconazole.. The re-emergence and the high mortality of mucormycosis in solid organ transplant receiver show the necessity to find new therapeutic approaches. Posaconazole associated with liposomal amphotericin B could be an interesting option to treat disseminated mucormycosis and improve their outcome.

Topics: Absidia; Adult; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Debridement; Female; Humans; Lung Diseases, Fungal; Lung Transplantation; Mucormycosis; Opportunistic Infections; Thyroid Diseases; Triazoles

We compared the activities of antifungal agents against a wide range of yeasts and filamentous fungi. The methodology of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for yeasts and spore-forming molds was applied; and a total of 349 clinical isolates of Candida spp., other yeast species, Aspergillus spp., and nondermatophyte non-Aspergillus spp. were investigated. The average geometric mean (GM) of the MICs of the various drugs for Candida spp. were as follows: amphotericin B (AMB), 0.55 microg/ml; liposomal amphotericin B (l-AMB); 0.35 microg/ml; itraconazole (ITC), 0.56 microg/ml; voriconazole (VRC), 0.45 microg/ml; posaconazole (POS), 0.44 microg/ml; and caspofungin (CPF), 0.45 microg/ml. The data indicated that the majority of Candida spp. were susceptible to the traditional and new antifungal drugs. For Aspergillus spp., the average GM MICs of AMB, l-AMB, ITC, VRC, POS, and CPF were 1.49 microg/ml, 1.44 microg/ml, 0.65 microg/ml, 0.34 microg/ml, 0.25 microg/ml, and 0.32 microg/ml, respectively. For the various zygomycetes, the average GM MICs of AMB, l-AMB, ITC, and POS were 1.36 microg/ml, 1.42 microg/ml, 4.37 microg/ml, and 1.65 microg/ml, respectively. Other yeastlike fungi and molds displayed various patterns of susceptibility. In general, the minimal fungicidal concentrations were 1 to 3 dilutions higher than the corresponding MICs. POS, AMB, and l-AMB showed activities against a broader range of fungi than ITC, VRC, and CPF did. Emerging pathogens such as Saccharomyces cerevisiae and Fusarium solani were not killed by any drug. In summary, the EUCAST data showed that the in vitro susceptibilities of yeasts and filamentous fungi are variable, that susceptibility occurs among and within various genera and species, and that susceptibility depends on the antifungal drug tested. AMB, l-AMB, and POS were active against the majority of pathogens, including species that cause rare and difficult-to-treat infections.

Topics: Amphotericin B; Antifungal Agents; Aspergillus; Candida; Drug Resistance, Fungal; Europe; Fungi; Guidelines as Topic; Humans; Microbial Sensitivity Tests; Mycoses; Opportunistic Infections; Triazoles; Yeasts

In this study the molecular identification and susceptibility profile of 21 clinical isolates, from a Brazilian hospital, belongs to six different species of Trichosporon were described. Trichosporon asahii was the predominant species and corresponded to 43% of isolates. Eighty three percent of the strains isolated from deep sites were identified as T. asahii, while only 17% belong to a non-T. asahii species (Trichosporon inkin). In general, the MICs were high and independent of the species of Trichosporon as well as the clinical origin of strain. Amphotericin B and fluconazole were less effective against Trichosporon spp. and high MIC values of voriconazole, posaconazole and ravuconazole were observed. Fifty-six percent (5/9) of T. asahii strains were isolated from deep sites, whereas 8% (1/12) of non-T. asahii species were isolated from those sites. A total of 89% of T. asahii isolates exhibited resistance to amphotericin B in vitro.

Topics: Amphotericin B; Antifungal Agents; Brazil; Cross Infection; Dermatomycoses; Drug Resistance, Fungal; Echinocandins; Female; Flucytosine; Fungemia; Hospitals, University; Humans; Mycological Typing Techniques; Mycoses; Onychomycosis; Opportunistic Infections; Organ Specificity; Triazoles; Trichosporon; Urine; Vaginitis

The authors report the clinical history of a patient having presented a cutaneous mucormycosis at the waning of a traumatic dilapidation post of the left lower limb. Mucormycosis is an opportunistic fungal infection due to fungi of the group of mucorales present in the environment. There are various clinical forms of the disease; it occurs generally in a predisposed environment. The diagnosis is based on the mycologic and pathologic examination. The therapeutic approach must be multidisciplinary; the vital and functional prognosis depends on early diagnosis and treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Leg Dermatoses; Male; Mucormycosis; Opportunistic Infections; Treatment Outcome

To present a clinical report of palatal zygomycosis, its epidemiological, mycological features, and our treatment experience.. Retrospective report.. This is a 25-year long retrospective trial of clinically and mycologically proven cases of zygomycosis. Some patients underwent a biopsy of the palatal lesion and autopsy. This study reports the treatment experience with amphotericin B alone and in combination with itraconazole and fluconazole.. Twenty-one cases (18.75%) of zygomycosis with palatal involvement were included in the study, from a total of 112 cases screened. Mean age was 36.5 years, with 18 adults and three children. The associated pre-disposing factors were: ketoacidotic diabetes (five type-1 and 15 type-2), and acute leukaemia in one patient. The clinical varieties were as follows: 19 cases of rhinocerebral (RC) involvement and two disseminated cases. Palatal ulcers occurred in 3/21 early cases (14.3%) and in 16/21 cases after the nasal involvement. All patients received amphotericin B; in four patients, it was combined with itraconazole and four with fluconazole. Clinical and mycological cure was achieved in 4/21 patients (19.04%).. Zygomycosis with palatal involvement occurs in around 18% of cases, usually associated with RC modalities; it has an acute and generally lethal course.

Topics: Absidia; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brain Diseases; Child; Diabetic Ketoacidosis; Drug Combinations; Female; Fluconazole; Humans; Itraconazole; Male; Mouth Diseases; Mucormycosis; Nose Diseases; Opportunistic Infections; Oral Ulcer; Palate; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Rhizopus; Treatment Outcome; Zygomycosis

Mucormycosis is a rare but potentially lethal fungal infection in renal allograft recipients with rhinocerebral mucormycosis is the most common presentation. The usual infection route is inhalation of the spores, but certain procedures such as intravenous cannulation and bladder catheterization are often the cause of infection.. A 50-year-old female dermatologist received an allograft from an emotionally related living donor, 24-year-old male with the same blood group and 3/6 mismatches. After severe attack of acute vascular rejection associated with rupture graft, that was managed properly she developed rinocereral mucormycosis. It was diagnosed early and aggressively treated with amphoteracin B and carefully monitored with favourable graft and patient survival. Up to our knowledge, this is the first case of renal transplant with extrarenal-ethemoidal sinus-mucor infection associated with acute vascular rejection that in spite of aggressive anti-rejection therapies with methylprednisolone, rituximab and plasma exchange, had favourable outcome in terms of graft and patient survival.. Mucormycosis in a renal allograft recipient is an extremely rare and potentially lethal complication. Aggressive anti-rejection therapy is a risk factor for the development of this unfavourable outcome. Early diagnosis, aggressive treatment with amphoteracin B and careful monitoring can be helpful in treating these patients and achieve favourable prognosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Mucorales; Mucormycosis; Opportunistic Infections; Transplantation, Homologous; Treatment Outcome

Cryptoccus neoformans meningitis (CNM) is an opportunistic infection that typically occurs in immunosuppressed patients. Subjects affected by sarcoidosis, a systemic granulomatous disease of unknown cause, are predisposed to CNM because of the impairment of cell-mediated immunity and because of the chronic corticosteroid therapy they frequently receive. Here we report the case of a 38-year-old man who developed CNM as the first clinical manifestation of sarcoidosis. The patient developed CNM even though he was apparently immunocompetent and was not on therapy with either corticosteroid or cytotoxic drugs.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Fatal Outcome; Flucytosine; Humans; Male; Meningitis, Cryptococcal; Opportunistic Infections; Risk Factors; Sarcoidosis, Pulmonary

To describe the clinical presentation, management, and outcomes of patients with Penicillium marneffei infections in a regional hospital in Hong Kong.. Retrospective study.. A regional and tertiary human immunodeficiency virus-referral hospital in Hong Kong.. Those who had penicilliosis during the inclusive period January 1994 to February 2004.. Forty-seven immunocompromised patients (44 being human immunodeficiency virus-positive) with penicilliosis were retrospectively studied. Fever, malaise, and anaemia were the commonest presentations. Most diagnoses were obtained from blood cultures (83%) and lymph node biopsies (34%). Five (11%) died, death being attributable to penicilliosis; four (9%) of them had received no specific antifungal treatment due to late presentation and late diagnosis. The CD4 count of human immunodeficiency virus-infected patients upon diagnosis of penicilliosis was low (median, 20.0 cells/mm3). Most (70%) patients received amphotericin B as an induction treatment, followed by oral itraconazole, although a smaller proportion (21%) received oral itraconazole only. All surviving human immunodeficiency virus-infected patients took highly active antiretroviral treatment and oral itraconazole as secondary prophylaxis after treatment of penicilliosis. The prognosis appeared satisfactory with early diagnosis and administration of appropriate antifungal therapy. Relapse ensued in two (4%) of the patients only.. Penicillium marneffei infection in immunocompromised patients is a serious disease with significant mortality if not diagnosed early and treated with appropriate antifungal drugs. Simple investigations like blood culture enable the diagnosis in the majority of cases. Immunocompromised patients who have been successfully treated should receive oral itraconazole as a maintenance therapy to prevent relapse.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Fungemia; Hong Kong; Humans; Infusions, Intravenous; Itraconazole; Lung Diseases, Fungal; Opportunistic Infections; Penicillium; Retrospective Studies; Survival Rate

We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections.. A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans.. Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment.. Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

Topics: Adult; Aged; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents, Alkylating; Brain Neoplasms; Cerebrospinal Fluid; Cryptococcus neoformans; Dacarbazine; Dexamethasone; Fatal Outcome; Fluconazole; Flucytosine; Glioma; Humans; Immunosuppression Therapy; Lomustine; Male; Meningitis, Cryptococcal; Opportunistic Infections; Temozolomide; Treatment Outcome

Descending mediastinitis occurs as a complication of oropharyngeal or cervical infections and its delayed diagnosis and treatment are associated with high mortality. A rare case of an odontogenic infection in a diabetic patient, complicated by Candida parapsilosis and Candida krusei parapharyngeal space infection, descending mediastinitis and aspiration pneumonia is described. Isolate identification was based on colonial and microscopic morphological characteristics and carbohydrate assimilation test results. The patient was successfully treated with surgical drainage and debridement, broad spectrum antibacterials and liposomal amphotericin B followed by prolonged oral voriconazole therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis, Oral; Diabetes Mellitus, Type 2; Female; Humans; Mediastinitis; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.

Topics: Antifungal Agents; Antineoplastic Agents; Antiparasitic Agents; Cell Line, Tumor; Depsipeptides; Drug Screening Assays, Antitumor; Fusarium; Humans; Lysosomes; Microbiological Techniques; Mycobacterium tuberculosis; Opportunistic Infections; Parasitic Sensitivity Tests; Receptor, ErbB-3; Structure-Activity Relationship

Invasive aspergillosis (IA) is a common fungal infection in immunocompromised patients and has a high mortality rate. Among patients with IA, Aspergillus terreus infections have become a growing concern in the past few years.. To determine the clinical risk factors for isolation of and respiratory infection by A terreus in patients with culture findings positive for filamentous fungi.. Cohort study of 505 consecutive isolates of filamentous fungi in 332 patients from one center. A terreus was present in 46 isolates from 40 patients (9.1%). Clinical histories were reviewed to identify the risk factors related to isolation of and infection by A terreus, which were grouped into three categories (ie, host factors, factors related to immunosuppression, and factors related to hospitalization), and were analyzed using a multiple logistic regression model.. A total of 192 of 505 isolates studied (38%) were due to invasive respiratory infection. A total of 27 of 46 cultures (58.7%) that were positive for A terreus were due to invasive infection (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.37 to 4.69; p = 0.034). The factors associated with invasive A terreus infection were prophylactic use of amphotericin B aerosols (OR, 27.8; 95% CI, 6.7 to 109.7; p = 0.001) and mechanical ventilation (OR, 3.3; 95% CI, 1.02 to 10.9; p = 0.04). Transplantation was associated with a lower risk of A terreus infection (OR, 0.2; 95% CI, 0.046 to 0.789; p = 0.02).. In patients with culture findings positive for filamentous fungi, the prophylactic use of amphotericin B aerosols and mechanical ventilation are associated with a higher risk of A terreus infections. In these patients, transplantation is associated with a lower risk of isolation and respiratory infection by A terreus.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Aspergillus; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Risk Factors

Primary cutaneous aspergillosis is a rare cutaneous disease that usually affects immunodepressed patients of any age. The most common associated disorders in children are leukemias and lymphomas although it can also occur in neonates and preterms due to their intrinsic immunological immaturity. We report the case of a 4-year-old boy diagnosed of acute lymphoblastic leukemia that, during chemotherapy, developed an ulceronecrotic inflammatory cutaneous lesion in the venopuncture area of the left forearm, and whose microbiological culture was positive for Aspergillus flavus.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus flavus; Child, Preschool; Dermatomycoses; Humans; Immunocompromised Host; Male; Neutropenia; Opportunistic Infections; Phlebotomy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Skin Ulcer; Wound Infection

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

Infections in immunocompromised children can stem from bacteria, fungi, viruses, or protozoa, but most importantly, from the host's endogenous bacterial flora. Disseminated infection caused by Trichosporon species is one of the emerging mycoses in neutropenic patients, particularly when they are treated for haematological malignancy with cytotoxic and immunosuppressive chemotherapy. We report a 15-year-old boy with acute lymphoblastic leukaemia, whose Trichosporon mucoides infection was successfully treated with lipid complex amphotericin B plus 5-fluorocytosine.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Flucytosine; Humans; Male; Mycoses; Opportunistic Infections; Trichosporon

Topics: Amphotericin B; Antifungal Agents; Dermatomycoses; Drug Resistance, Fungal; Endophthalmitis; Exophiala; Female; Fungemia; Humans; Itraconazole; Middle Aged; Mycoses; Opportunistic Infections; Osteolysis; Pregnancy; Pregnancy Complications, Infectious; Pyrimidines; Recurrence; Th2 Cells; Triazoles; Voriconazole

Cryptococcus neoformans has emerged as an important opportunistic fungal pathogen in immunocompromised individuals. The therapeutic options of C. neoformans an opportunistic fungal pathogen include flucytosine, amphotericin B, and azole agents. However in the present scenario, emergence of resistance has been reported, hence this study was undertaken to evaluate antifungal susceptibility pattern of C. neoformans isolates from this southern part of India. Ten isolates of C. neoformans were tested against Amp B and fluconazole, of which 7 were susceptible to both and a single isolate of C. neoformans var gatti was resistant to both with MIC of 32mg/ml and 64mg/ml respectively.

Topics: Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Humans; In Vitro Techniques; India; Meningitis, Cryptococcal; Opportunistic Infections

We present the case of a 74-y-old HIV-negative female who suffered simultaneously from multiple opportunistic infections and a Klebsiella pneumoniae sepsis during high-dose steroids for giant cell arteritis. The patient was treated with a purine analog due to hairy cell leukaemia 10 y previously. Purine analog therapy can lead to long lasting defects in cell-mediated immunity. In these patients, treatment with steroids should be closely monitored with CD4 counts.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Cladribine; Cytomegalovirus; Dexamethasone; Esophagitis; Female; Giant Cell Arteritis; Herpes Simplex; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leukemia, Hairy Cell; Methylprednisolone; Opportunistic Infections; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination

Leishmaniasis is an infection caused by a protozoan parasite belonging to genus Leishmania and transmitted by the Phlebotomus sandfly. Clinical presentations of infection include visceral, cutaneous, and mucocutaneous forms. Leishmaniasis is endemic in Africa, Asia, Europe, South America, and southern part of North America. This infection is extremely rare in the US and is mostly found among travelers coming from endemic areas. Cases of cutaneous and visceral leishmaniasis have been reported in organ transplant recipients in endemic areas.. We describe a case of cutaneous leishmaniasis in a kidney transplant patient, originally from Bolivia, who resides in the area known to be non-endemic for leishmaniasis and who is known not to travel within or outside of the US after the transplantation.. Histologic examination of cutaneous lesion revealed extensive subcutaneous lymphohistiocytic inflammation with clusters of amastigote within histiocytes.. To our knowledge, this is the first case of cutaneous leishmaniasis in a kidney transplant patient residing in the US in an area known to be non-endemic for leishmaniasis, probably after reactivation of a previously dormant infection acquired outside of the US at least 9 months prior to developing clinical symptoms.

Topics: Amphotericin B; Antiprotozoal Agents; Female; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leishmaniasis, Cutaneous; Middle Aged; Opportunistic Infections; Skin Diseases, Infectious

Topics: Amphotericin B; Antifungal Agents; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mycoses; Opportunistic Infections; Saccharomyces cerevisiae

Invasive Acremonium infection in humans is rare. We report a patient with leukemia who developed pyomyositis due to Acremonium species. Painful cutaneous nodules and severe myalgia were the first clinical manifestations during the neutropenic stage after chemotherapy. Magnetic resonance image (MRI) revealed multiple nodular lesions scattered along the intramuscular regions of the lower legs. Culture of an aspiration grew Acremonium species. Surgical drainage was performed. Although all antifungal agents tested showed no in vitro inhibitory activity, we successfully treated this patient with amphotericin B, granulocyte colony-stimulating factor (G-CSF), and surgical drainage.

Topics: Acremonium; Acute Disease; Adolescent; Amphotericin B; Drainage; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Mycoses; Neutropenia; Opportunistic Infections

The exposure to Aspergillus organisms/spores is likely common, but disease caused by tissue invasion with these fungi is uncommon and occurs primarily in the setting of immunosuppression. We report a case of rapidly advancing invasive endomyocardial aspergillosis secondary to prolonged usage of multiple broad-spectrum antibiotics in a nonimmunocompromised host. A 36-year-old cotton textile worker presented to our institution with a 3-month history of weight loss and fatigue. He reported receiving prolonged use of multiple broad-spectrum antibiotic treatment. The echocardiogram demonstrated multiple endomyocardial vegetations and a mass in the left atrium. Myocardial biopsy specimen revealed an invasive endomyocardial aspergillosis. The patient was investigated for immune deficiency including HIV, and this workup was negative. Treatment was started with amphotericin B and heparin for presumed left atrial thrombus. The patient died because of a rupture of mycotic aneurysm that resulted in cerebral hemorrhage. This case illustrates the risk of an invasive fungal infection in a nonimmunocompromised host who is a prolonged user of antibiotics in the setting of environmental exposure of opportunistic invasive fungal infections.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cardiomyopathies; Cerebral Hemorrhage; Fatal Outcome; Humans; Intracranial Aneurysm; Male; Opportunistic Infections; Rupture; Ultrasonography; Urinary Tract Infections

The objective was to prospectively assess the efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the caspofungin compassionate-use study.. Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s). Efficacy was assessed at end of intravenous caspofungin therapy based on the clinical (symptom/sign and radiographic) response.. Underlying diseases included hematological malignancy (69%), organ transplant (8%), and AIDS (6%). Forty-three (90%) patients were refractory to prior antifungal treatment, including 25 patients refractory to multiple agents. Sixteen (33%) were neutropenic at study entry. Following caspofungin therapy, a favorable response was noted in 44% (20/45) of the patients, including nine (20%) and 11 (24%) patients with complete and partial responses, respectively. Caspofungin was generally well tolerated one serious drug-related adverse event was reported.. In this study, caspofungin was an effective alternative for patients with refractory Aspergillus infections.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Child; Drug Therapy, Combination; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Peptides, Cyclic; Salvage Therapy

Endogenous Candida endophthalmitis is a rare disease with increasing frequency and poor prognosis.. The course of endogenous Candida endophthalmitis in 7 eyes of 5 patients (age 2 months to 76 years) was evaluated. Underlying general diseases were diagnosed as colon cancer, diverticulitis, pancreatic insufficiency (with subclavian catheter), ileus and diabetes mellitus. Diagnosis was based on the very typical ocular feature combined with a positive blood or vitreous culture. Intensive antimycotic drug therapy was initiated and pars plana vitrectomy performed as soon as possible.. The delay between onset of ocular symptoms and diagnosis amounted to one week and 2 months. In 3 eyes of 2 patients no vitrectomy could be done because of the very impaired state of health. These patients died of their general diseases one week and 2 months, respectively, later. During follow-up (4 weeks to 51 months) three eyes reached visual acuity of 5/10, 4/10 and 1/10. One eye reached 1/20 after additional surgery because of retinal detachment. In all vitrectomized eyes the diagnosis was substantiated by a positive culture of vitreous fluid. No recurrence of ocular inflammation was observed.. Early vitrectomy seems to be mandatory in each case which is suspected of Candida endophthalmitis. Only with this option it is possible to fix the diagnosis and initiate adequate therapy in due time in order to improve the original poor prognosis.

Topics: Aged; Amphotericin B; Anterior Chamber; Antifungal Agents; Candidiasis; Endophthalmitis; Female; Fungemia; Gentamicins; Humans; Infant, Newborn; Infant, Premature, Diseases; Injections; Male; Ophthalmic Solutions; Opportunistic Infections; Prednisone; Risk Factors; Treatment Outcome; Vitrectomy; Vitreous Body

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the 'proven' group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Cyclosporine; Female; Graft Survival; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Infant; Liposomes; Male; Middle Aged; Mycoses; Opportunistic Infections

The efficacy and renal safety of amphotericin B lipid complex (ABLC) were assessed in 398 patients with invasive aspergillosis. The most common underlying conditions were hematopoietic stem-cell transplantation (101/398 [25%]), hematologic malignancy (101/398 [25%]), and solid-organ transplantation (109/398 [27%]). The most common reason for administration of ABLC was lack of response to prior antifungal therapy. Overall, 65% of patients had a favorable clinical response: 44% were cured or improved, and 21% were stabilized. Clinical responses were similar for patients who received ABLC as either first-line or second-line therapy. One hundred forty-four patients whose results could be evaluated received ABLC concurrently with or after therapy with itraconazole. No antagonism was observed when therapy with ABLC followed therapy with itraconazole. Patients infected with Aspergillus terreus, an innately polyene-resistant species, experienced a 37% response rate. Changes in serum creatinine levels were not clinically significant in most patients; however, dialysis was initiated in 7 patients, of whom 6 had prior antifungal therapy or preexisting renal disease. Analysis of this large database demonstrated the efficacy and safety of ABLC in the treatment of invasive aspergillosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Drug Combinations; Female; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Registries; Treatment Outcome

An assessment was made of the efficacy and renal safety of amphotericin B lipid complex (ABLC) in the treatment of patients with invasive fungal infections caused by moulds other than Aspergillus species, on the basis of a retrospective analysis of data from the Collaborative Exchange of Antifungal Research (CLEAR) database. Data from CLEAR for 64 patients with zygomycosis were published previously. The database was further queried and yielded results for 28 patients with fusariosis and 84 patients infected with other non-Aspergillus moulds. Of 26 patients with fusariosis whose results could be evaluated, 46% (n = 12) were cured or improved, and an additional 12% (n = 3) were stable. Of 79 patients infected with other non-Aspergillus moulds whose results could be evaluated, 61% (n = 48) were cured or improved, and an additional 15% (n = 12) were stable. In an area with little guidance for therapy, the CLEAR data indicate that ABLC can be an effective broad-spectrum treatment choice for several invasive and refractory non-Aspergillus mould infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Drug Combinations; Female; Fusarium; Humans; Immunocompromised Host; Infant; Kidney; Male; Middle Aged; Mycoses; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Registries; Retrospective Studies; Treatment Outcome; Zygomycosis

The efficacy and renal safety of amphotericin B lipid complex (ABLC) injection were assessed in 106 patients with cryptococcal infection. Eighty-three patients (78%) had a central nervous system (CNS) infection. Of these patients, 20 initiated azole therapy concomitantly with ABLC therapy, and 7 had received prior azole therapy, which continued during administration of ABLC. Clinical response (cured or improved) was achieved in 67 (66%) of 101 patients whose results could be evaluated. Response rates were 65% (51/78) for patients with a CNS infection and 70% (16/23) for patients without a CNS infection. The response rate for patients with HIV infection was 58% (30/52). Response rates were 56% (19/34) for patients who were refractory to prior antifungal therapy, 65% (11/17) for patients who were intolerant of prior antifungal therapy, 60% (3/5) for patients with underlying renal disease who received prior antifungal therapy, 76% (25/33) for patients with underlying renal disease who did not receive prior antifungal therapy, and 73% (8/11) for patients with no renal disease who did not receive prior antifungal therapy. A mean serum creatinine level decrease of 0.02 mg/dL occurred. ABLC was an effective treatment for cryptococcal infection in immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Combinations; Female; Humans; Immunocompromised Host; Male; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Registries; Treatment Outcome

Antifungal prophylaxis has been proposed for liver transplant recipients at increased risk for invasive mold infection. Risk factors for invasive mold infection after liver transplantation were selected to divide recipients into 3 groups: (1) high risk-transplantation on hemodialysis or delay of hospital discharge beyond day 7 after transplantation because of allograft or renal insufficiency; (2) intermediate risk-retransplantation or transplantation for fulminant hepatic failure; (3) low risk-absence of conditions in groups 1 and 2. During an intervention period (February 1999-April 2001), prophylactic administration of a lipid complex of amphotericin (Abelcet) at 5 mg/kg intravenously every 24 to 48 hours was recommended for high-risk recipients. The frequency of mold infection was compared to that of a preintervention period (February 1998-January 1999) when antifungal prophylaxis was not provided. During the intervention period, invasive mold infection developed in 2 (6%) of 35 high-risk recipients, 0 of 28 intermediate-risk recipients, and 1 (0.5%) of 187 low-risk recipients. Overall, of 58 liver transplant recipients, 3 (5%) developed an invasive mold infection during the preintervention period, compared with 3 (1%) of 250 during the intervention period (P = 0.08). The only death from invasive mold infection occurred during the preintervention period. Rates of pulse corticosteroid treatment of rejection and cytomegalovirus infection were lower during the intervention period. In conclusion, readily identifiable patient characteristics can be used to stratify liver transplant recipients for risk of invasive mold infection. Antifungal prophylaxis given to high-risk recipients may provide cost-effective prevention of these infections.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Cohort Studies; Drug Administration Schedule; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Liver Transplantation; Male; Opportunistic Infections; Postoperative Complications; Preoperative Care; Probability; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Treatment Outcome

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

We report the first case of Phialemonium obovatum fungemia with subsequent caseating granulomatas in the lung and Crohn disease-like involvement of the gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus has been rarely described as an opportunistic infection in immunosuppressed patients. The patient was diagnosed with chronic myelogenous leukemia and underwent subsequent peripheral bone marrow transplant. After 6 months, he developed graft-versus-host disease of the skin and liver with fever and severe diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative. Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy of the lesion showed septate branching hyphae (4-5 microm in diameter) with terminal globular structures (10 microm in diameter). The hyphae were similar in width to that of an Aspergillus species but had a more moniliform appearance. Blood cultures grew a pure culture of P. obovatum. He was treated with amphotericin B and itraconazole for 6 months without remission of the diarrhea. Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with marked crypt distortion simulating Crohn disease. In retrospect, the fungus was found to be resistant to both of the aforementioned drugs and susceptible to voriconazole and posaconazole. The gastrointestinal findings raise the possibility of further dissemination of a partially treated Phialemonium infection.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Bone Marrow Transplantation; Drug Resistance, Fungal; Fungemia; Gastrointestinal Diseases; Graft vs Host Disease; Granuloma; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

A total of 85 allogeneic hematopoietic cell transplant (HCT) recipients with invasive aspergillosis treated with amphotericin B lipid complex (ABLC) were identified from the Collaborative Exchange of Antifungal Research (CLEAR) database. Of these patients, 78% (66/85) presented with pulmonary aspergillosis. Graft-versus-host disease (GVHD) was present in 24 of 85 patients. The response rate to ABLC was 31% (26/85) overall and 21% (5/24) in patients with GVHD. The overall response rate to first-line ABLC treatment was 41% (11/27). Four of nine (44%) patients with GVHD responded to first-line treatment with ABLC, while only one of 13 (8%) responded to ABLC as second-line therapy. Five of 18 (28%) and four of 14 (29%) patients, respectively, responded to sequential or concurrent treatment with ABLC and itraconazole. None of seven patients responded who continued receiving itraconazole after the start of ABLC therapy. At the end of ABLC therapy, serum creatinine had doubled in 12% of patients (10/85), and 2% (2/85) had developed a requirement for dialysis. These data suggest that ABLC, especially when administered as first-line therapy, can result in clinical response even in the most immunocompromised patients, that is, HCT recipients with GVHD, with minimal effects on renal function.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Child; Child, Preschool; Databases, Factual; Drug Combinations; Drug Evaluation; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies; Transplantation, Homologous; Treatment Outcome

Aspergillus terreus, a less common pathogen, appears to be an emerging cause of infection at our institution, the Medical University Hospital of Innsbruck. Thus the epidemiology and outcome of A. terreus infections over the past 10 years was assessed. We analysed 67 cases of proven invasive aspergillosis (IA) according to the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria, investigated antifungal susceptibility of amphotericin B (AMB), voriconazole and caspofungin and performed molecular typing of A. terreus. Patients with proven IA caused by A. terreus (n = 32) and non-A. terreus (n = 35) were evaluated. The two groups were comparable in terms of age, gender, underlying disease, antifungal prophylaxis and duration of neutropenia (P > 0.05). Leukaemia was the most common underlying malignancy. Fungal dissemination occurred in 63% of the patients. Aspergillus terreus infections were associated with a lower response rate to AMB therapy (20%), compared with 47% for patients with non-A. terreus infections (P < 0.05). In vitro, A. terreus was found to be resistant to AMB and molecular typing discriminated between patients isolates, showing a high strain diversity with 26 distinct types (I-XXVI) identified by combination of three primers. Aspergillus terreus infections displayed evidence of AMB resistance in vitro and in vivo and were associated with a high rate of dissemination and poor outcome; A. terreus causes systemic infections of endemic character in Tyrol, Austria. The onset of A. terreus infection depends not on the degree of immunosuppression but on environmental Aspergillus spp. exposure.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Austria; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Genes, Fungal; Hematologic Neoplasms; Humans; Lipopeptides; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Peptides, Cyclic; Prevalence; Pyrimidines; Retrospective Studies; Treatment Outcome; Triazoles; Voriconazole

In recent years, the incidence of HIV infection, the intensity of chemotherapy regimens for cancer and the use of bone marrow transplantation have all increased. This results in an increase in the incidence of systemic fungal infections, which are associated high rates of morbidity and mortality in this immunosuppressed population; the incidence is growing: 50% for neutropenic/transplant bone marrow patients and 5-20% for organ transplant. Fluconazole, itraconazole, amphotericin-B and, in the recent years, caspofungin and voriconazole are the most frequently used antifungal agents. However, the newly developed formulations of itraconazole and lipid-associated formulations of amphotericin-B have provide new treatment options for systemic fungal infection and have prompted a number of comparisons of the treatment costs of empirical therapy. The i.v. formulation of itraconazole may be more cost effective than either conventional or liposomial formulations of amphotericin-B when used as empirical therapy for neutropenic patients with persistent fever despite broad spectrum antibiotic therapy, but further studies are required. The lack of studies, national and international, and the small amount of available data on the cost of systemic fungal infections mean that the costs saving from prophylactic and empirical use of antifungals are difficult to estimate.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Fluconazole; Humans; Immunocompromised Host; Itraconazole; Lipopeptides; Mycoses; Neutropenia; Opportunistic Infections; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis. It occurs almost exclusively in the late posttransplantation period (>6 months after the initiation of immunosuppression). Subclinical onset of meningitis is the usual clinical presentation. Despite initiation of therapy, the mortality rate associated with this infection in this patient population remains high. To the best of our knowledge, this report describes one of the first cases of a rare entity: a primary cutaneous cryptococcosis in a renal transplant recipient disclosed by skull osteomyelitis and pseudotumoral intracranial extension. Surgical debridement and azole antifungal therapy were performed. Ten months after the onset of treatment, the patient feels good, clinical examination findings are normal, and no sign of evolutive cryptococcosis is noted.

Topics: Abscess; Amphotericin B; Animals; Antifungal Agents; Combined Modality Therapy; Cryptococcosis; Debridement; Diagnosis, Differential; Ducks; Environmental Exposure; Facial Injuries; Fluconazole; Graft Rejection; Granuloma; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Osteitis; Osteolysis; Parietal Bone; Postoperative Complications; Remission Induction; Seminoma; Skull Neoplasms; Subcutaneous Tissue; Testicular Neoplasms

Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy.. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André.. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D.. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles.. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Retrospective Studies; Treatment Outcome

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

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

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

Chronic granulomatous disease is an inherited defect in host defense mechanisms mainly affecting neutrophil function. Pulmonary infection with Aspergillus nidulans in a child with chronic granulomatous disease could not be eliminated by a combination of caspofungin and liposomal amphotericin B. Voriconazole was successful in clearing the infection.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus nidulans; Caspofungin; Drug Therapy, Combination; Echinocandins; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Lipopeptides; Lung Diseases, Fungal; Male; Opportunistic Infections; Peptides; Peptides, Cyclic; Pyrimidines; Risk Assessment; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

A woman of 75 years old was admitted at our hospital for evaluation of worsening and weakness in inferior limbs. Several vertebral fractures by crushing, one doubtful discitis, an infiltrate with cavitation in the right superior lobe and one infiltrate in the left superior lobe were detected. In the biopsy of the consolidation a filamentous fungus was watched and in the bronchial washing specimen culture grew Aspergillus terreus. The infiltrates disappeared with liposomal Amphotericin B remaining with oral Itraconazol during three months more. The clinical and analytical data demonstrate the existence of a Overlap syndrome associate to antiphospholipid-antibody syndrome. We comment the peculiarity of the infection by Aspergillus terreus in patients who have not been in critical care and the good response at treatment with liposomal Amphotericin B. It contrasts with the high mortality referred in a recent review. Other aspects to comment are the coexistence with a collagen vascular and an antiphospholipid-antibody syndrome with the higher titles of IgM ACA that we have found in literature.

Topics: Aged; Amphotericin B; Antifungal Agents; Antiphospholipid Syndrome; Aspergillosis; Aspergillus; Autoimmune Diseases; Drug Therapy, Combination; Female; Gastritis, Atrophic; Helicobacter Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Itraconazole; Liposomes; Lung Diseases, Fungal; Opportunistic Infections; Prednisone; Purpura, Thrombocytopenic, Idiopathic

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Topics: Adult; Age Distribution; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Cause of Death; Central Nervous System Fungal Infections; Critical Illness; Female; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Neuroaspergillosis; Opportunistic Infections; Retrospective Studies; Risk Assessment; Sex Distribution; Survival Analysis; Thailand

Bilateral invasive renal mucormycosis has previously been associated with a 100% mortality rate. We report a case of bilateral invasive renal mucormycosis in a patient treated with amphotericin B and bilateral nephrectomy who survived and is currently disease-free.

Topics: Adult; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Humans; Male; Mucormycosis; Nephrectomy; Opportunistic Infections; Pyelitis; Remission Induction

Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus.. The authors retrospectively reviewed the medical records of 300 patients who received care at our institution between 1995 and 2001 and who had cultures that were positive for Aspergillus infection, including 90 patients whose cultures were positive for A. fumigatus and 70 patients whose cultures were positive for A. terreus.. Thirty-two patients with IA caused by A. terreus and 33 patients with IA caused by A. fumigatus were evaluated. The two groups were comparable in terms of age, gender, and underlying disease. Leukemia was the most common underlying malignancy (84%). More than 40% of patients in each group had undergone bone marrow transplantation. There was a trend toward a higher frequency of neutropenia among patients with IA caused by A. terreus (P = 0.12). IA caused by A. terreus was considered to be nosocomial in origin significantly more frequently compared with IA caused by A. fumigatus (P = 0.03). In vitro, A. terreus was found to be more resistant to amphotericin B (minimal inhibitory concentration [MIC90], 4.0 microg/mL) than to antifungal therapy (MIC90, 1.0 Hg/mL) in the isolates that were tested (< 50% of all isolates). The overall rate of response to antifungal therapy was 39% for patients with A. fumigatus infection, compared with 28% for patients with A. terreus infection (P = 0.43).. Despite the decreased in vitro susceptibility of A. terreus (relative to A. fumigatus) to amphotericin B, the two groups within the current patient population had comparably poor responses to amphotericin B preparation and somewhat improved responses to posaconazole.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Aspergillus; Aspergillus fumigatus; Cross Infection; Drug Resistance, Fungal; Female; Humans; Leukemia; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Risk Factors; Triazoles

Although cases of pulmonary mucor are scarce, diabetics account for a large percentage of these patients. The synergism of diabetes mellitus and mucormycosis poses potentially devastating bronchopulmonary complications, warranting urgent intervention. This report reviews the efficient workup, along with successful medical and surgical management, of a patient with pulmonary mucormycosis, with evidence of superior vena cava invasion.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Diabetes Complications; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Pneumonectomy; Smoking; Tomography, X-Ray Computed; Vena Cava, Superior

Fungal infections are an important complication of lung transplantation, but no controlled studies of their management have been performed. Knowledge of actual anti-fungal strategies may aid in the design of future prospective studies.. Thirty-seven of 69 active lung transplant centers, accounting for 66% of all US lung transplantations, responded to our survey. The survey focused on fungal surveillance, pre- and post-transplant prophylaxis, and approach to fungal colonization.. The median number of lung transplantations performed by the centers in 1999 was 14 per year (range, 1-52), and median time that centers were in in operation was 9 years (range, 2-15 years). Seventy percent of centers had a transplant infectious diseases specialist. Pre-transplant fungal surveillance was performed by 81% of centers, with 67% of these surveying all patients and the remainder surveying only sub-sets of patients. Seventy-two percent of all centers started anti-fungal treatment if Aspergillus spp were isolated before transplantation. Itraconazole was the preferred agent (86%). After transplantation, 76% of centers gave anti-fungal prophylaxis, although 24% of these did so only in selected patients. Prophylactic agents in order of preference were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than 1 agent. Prophylaxis was initiated within 24 hours by 71% and within 1 week by all centers. Median duration of prophylaxis was 3 months (range, <1 month-lifetime). All 37 centers used anti-fungal therapy if colonization with Aspergillus spp was detected for a median duration of 4.5 months. Itraconazole was the preferred agent. Only 59% of centers treated patients colonized with Candida spp. In a statistical analysis, centers with larger volumes were less likely to treat pre-transplant colonization with Candida spp but more likely to use agents other than itraconazole for post-transplant colonization with Aspergillus spp. Only 14% of centers engaged in any anti-fungal research at the time of the survey.. The majority of surveyed lung transplant programs actively manage fungal infection with prophylaxis or pre-emptive therapy, despite the absence of controlled trials. This survey may provide an impetus and a basis for designing prospective studies.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bronchoscopy; Candidiasis; Health Care Surveys; Humans; Itraconazole; Lung Diseases, Fungal; Lung Transplantation; Opportunistic Infections; Premedication; United States

An immunosuppressed patient who presented with unusual clinical signs of cutaneous alternariosis, including papular, nodular and verrucous lesions of the forearms, is reported. In spite of continuous treatment with oral itraconazole for 6 months, a large, progressive, necrotic ulcer appeared on the patient's left leg. Liposomal amphotericin B was then administered (total dose, 750 mg) with excellent clinical results.

Topics: Alternaria; Amphotericin B; Antifungal Agents; Biopsy, Needle; Dermatomycoses; Follow-Up Studies; Humans; Immunocompromised Host; Immunohistochemistry; Kidney Transplantation; Leg Ulcer; Liposomes; Male; Middle Aged; Opportunistic Infections; Recurrence; Risk Assessment; Severity of Illness Index; Treatment Outcome

Pseudomembranous tracheobronchial aspergillosis coincident with systemic pulmonary aspergillosis represents a rare manifestation of fungal infection in immunocompromized hosts. We report on a patient with recurrent Hodgkin's disease, showing this infectious pattern after treatment with corticosteroids within the antineoplastic schedule, whereas neutropenia--the main risk factor for mold infections--had not occurred. An impaired number of helper T lymphocytes was merely detected as an additional, but hypothetical risk factor, when investigating the status of immunosuppression. Treated systemically with amphotericin B, the patient recovered quickly, although reported mortality rates are disastrous. What is crucial for the clinical management is an early diagnosis by bronchoscopy and cultural proof of the pathogen followed by an adequate antifungal treatment.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bronchoscopy; Female; Hodgkin Disease; Humans; Immunocompromised Host; Lung Diseases, Fungal; Middle Aged; Neutropenia; Opportunistic Infections; Tracheal Diseases

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF).. A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications.. A university hospital.. Lung transplant recipients with CF or other indications for transplantation.. None.. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients.. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cystic Fibrosis; Female; Heart Transplantation; Humans; Lung Diseases, Fungal; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Risk Factors; Wisconsin

Amphotericin B deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/day) was gradually increased to 2.0 mg/kg/day when renal function remained stable and the drug was tolerated. Dose escalation was possible without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied <18% of AmB-d infusions. Twenty-seven patients had a decrease in creatinine clearance while receiving AmB-d therapy. A >2-fold decrease in creatine clearance was observed in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to be well tolerated by most patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Cohort Studies; Deoxycholic Acid; Drug Combinations; Female; Humans; Immunocompromised Host; Infusion Pumps; Male; Middle Aged; Mycoses; Nausea; Neutropenia; Opportunistic Infections; Treatment Outcome

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

Systemic fungal infections have high mortality, and therapy is often toxic. Caspofungin acetate, a new antifungal agent with minimal toxicity, may provide a better alternative to typical therapy for Candida krusei.. Case report.. Multidisciplinary intensive care unit (ICU) of a community teaching hospital.. A 22-yr-old male with acute lymphoblastic leukemia and Candida krusei fungemia failed therapy with fluconazole and amphotericin B.. Caspofungin acetate given intravenously as a 70-mg loading dose, followed up by 50 mg daily along with standard ICU care.. Survival without toxicity from therapy.. Efficacy of caspofungin acetate in a patient with life-threatening Candida Krusei infection.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Fluconazole; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Male; Neutropenia; Opportunistic Infections; Peptides; Peptides, Cyclic; Pleural Effusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tomography, X-Ray Computed; Treatment Outcome

We present two cases of nosocomial urinary tract infection due to Trichosporon asahii in intensive care unit patients with bladder catheter from two hospitals in Santiago, Chile. Both patients had an several catheters and bacterial infections that required the use of antibiotic therapy. One strain showed in vitro resistance to amphotericin B. Both strains were susceptible to fluconazole, but presented MIC with dose-dependent susceptibility to ketoconazole and itraconazole. This is the first report showing T. asahii as urinary tract infection agent in Chile.

Topics: Amphotericin B; Antifungal Agents; Chile; Communicable Diseases, Emerging; Cross Infection; Drug Resistance, Fungal; Fatal Outcome; Fluconazole; Humans; Immunocompromised Host; Intensive Care Units; Itraconazole; Ketoconazole; Male; Microbial Sensitivity Tests; Middle Aged; Multiple Myeloma; Mycoses; Opportunistic Infections; Parkinson Disease; Postoperative Complications; Trichosporon; Urinary Catheterization; Urinary Tract Infections; Ventriculoperitoneal Shunt

Ina 24-month-old girl with acute lymphoblastic leukemia and invasive aspergillosis, only combination therapy with liposomal amphotericin B and caspofungin achieved a good response. Combination therapy could be a useful treatment option in children with invasive fungal disease, but before it can be routinely recommended, carefully controlled in vivo studies and well-designed randomized clinical trials are needed.

Topics: Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Caspofungin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Echinocandins; Female; Follow-Up Studies; Fungemia; Humans; Infant; Lipopeptides; Liposomes; Opportunistic Infections; Peptides; Peptides, Cyclic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Assessment; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

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

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

We report two cases of Acremonium fungemia with proven involvement of the skin and probably of the lung in patients who were both undergoing chemotherapy, one for mantle cell lymphoma and the other for acute lymphoblastic leukemia. Both patients failed amphotericin B deoxycholate treatment and were successfully treated with voriconazole with very mild toxicity.

Topics: Acremonium; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Female; Fungemia; Humans; Lymphoma, Mantle-Cell; Middle Aged; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Triazoles; Voriconazole

We report a case of invasive trichosporonosis due to Trichosporon beigelii originating in the left wrist of a bone marrow transplant recipient who was receiving caspofungin acetate as prophylaxis against invasive Aspergillus infection. While the patient's neutrophil count was recovering, treatment with fluconazole and amphotericin B lipid complex resulted in a complete clinical response.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Caspofungin; Chemoprevention; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; Lipopeptides; Male; Mycoses; Opportunistic Infections; Peptides; Peptides, Cyclic; Trichosporon

Candida arthritis is quite rare and might be caused either by direct intra-articular inoculation of Candida or secondary to hematogeneous seeding of Candida in immunocompromised hosts. Until now less than 50 cases of Candida arthritis have been reported in the literature. We report a case of Candida arthritis, which occurred in a patient with chronic myelogenous leukemia (CML) in blastic transformation. Aggressive chemotherapy and broad-spectrum antibiotics for a prolonged period for febrile neutropenia had been given to the patient. Arthritis of the left knee appeared during the recovery phase of leukopenia. Despite treatment with fluconazole, no clinical or microbiological improvement was obtained. Thus, administration of liposomal amphotericin B was started and after 3 days there was improvement. We can conclude that fluconazole might not be sufficient in some Candida arthritis cases and liposomal amphotericin B might be a good alternative in these resistant cases.

Topics: Amphotericin B; Arthritis, Infectious; Blast Crisis; Candidiasis; Drug Combinations; Drug Resistance; Fatal Outcome; Female; Fluconazole; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols

In this report we analyse the risk factors, the clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed an Invasive Fungi Infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients, from 5 of the participating centres. The primary localization of infection was lung in 10 cases and skin and paranasal sinus in 1 case each. Ten patients died at the end of follow up. The death was mainly attributable to IFI progression in nine of them. The factors that appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localization at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.

Topics: Adult; Aged; Amphotericin B; Data Collection; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycoses; Myelodysplastic Syndromes; Opportunistic Infections; Risk Factors; Treatment Outcome

Invasive pulmonary aspergillosis is frequent in neutropenic patients. Usually localized in the beginning, the disease spreads and mortality is high despite antifungal treatment. The role of early adjuvant surgery is not clear. Surgery may help to confirm fungal disease, may control fungal disease locally and may prevent systemic spreading. This study examines effects of early resection on survival and dissemination in a rat model of localized invasive pulmonary aspergillosis.. Forty persistently neutropenic male albino rats were challenged with standardized conidial aspergillus inoculum injected into peripheral lung tissue of the right upper lobe under direct vision. Animals were divided into four groups. Twenty animals were treated with amphotericin B at 1 mg/kg per day beginning 48 h after inoculation, 20 animals were left untreated. In each group half the animals underwent early resection of localized invasive aspergillosis by lobectomy. Animals were checked daily and mortality was recorded up to 28 days after which surviving animals were sacrificed.. Significantly higher survival was observed in resected animals in the non-Am B groups (survival: 10 +/- 19% without early resection and 50 +/- 32% with early resection; P = 0.044). However, early resection did not lead to improved survival in animals treated with amphotericin B (survival 70 +/- 29% without early resection and 50 +/- 32% with early resection; P = 0.316).. In this rat model of localized invasive pulmonary aspergillosis effects of early resection on survival could be demonstrated only in animals not receiving amphotericin B treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Combined Modality Therapy; Disease Models, Animal; Lung Diseases, Fungal; Male; Neutropenia; Opportunistic Infections; Rats; Rats, Sprague-Dawley; Survival Rate

A 48-year-old man with a history of sarcoidosis was transferred to the Mayo Clinic for evaluation and management of progressive neurologic decline. Two years before admission, he was admitted to a local hospital with mental status changes accompanied by ataxia and severe headache. A diagnosis of pulmonary and central nervous system sarcoidosis was made based on computed tomography of the head, lumbar puncture, and chest radiography. A mediastinoscopy with lymph node biopsy exhibited noncaseating granulomas and negative stains for microorganisms. Prednisone therapy was initiated at 80 mg/day. Clinical improvement was apparent for 13 months during steroid therapy until the slow taper reached a dosage of 20 mg/day. At that time, the patient was readmitted to the local hospital with severe confusion and skin lesions. When intravenous methylprednisolone therapy for presumed central nervous system sarcoidosis did not improve the patient's mental status, he was transferred to the Mayo Clinic. Physical examination of the thighs revealed large, well-marginated, indurated, irregularly bordered, violaceous plaques and rare, umbilicated, satellite papules with central hemorrhagic crusts (Fig. 1A). Superficially ulcerated plaques with a similar appearance to the thigh lesions were coalescing around the lower legs (Fig. 1B). A skin biopsy specimen of the thigh demonstrated abundant numbers of encapsulated organisms and minimal inflammatory response (Fig. 2). Skin, blood, and cerebrospinal fluid cultures confirmed the presence of Cryptococcus neoformans. Amphotericin and flucytosine combination therapy was initiated, and steroid dosages were gradually tapered. A test for human immunodeficiency virus was negative. The patient was dismissed from hospital after a complicated 2-month course resulting in improved mental status but progression of the lower extremity ulcerations as a result of polymicrobial infection.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Flucytosine; Humans; Male; Middle Aged; Opportunistic Infections; Sarcoidosis

We compared the in vitro antifungal activity of amphotericin B lipid complex (ABLC) with that of itraconazole (ITZ) against 535 yeast strains and 173 opportunistic filamentous fungi by using a microdilution method (National Committee for Clinical Laboratory Standards M27-A and M38-P). The overall geometric mean MIC was 0.13 microg/ml and 0.177 microg/ml for ITZ and ABLC, respectively, and the MIC(50) was 0.125 microg/ml for both agents against yeast isolates. ITZ had a similar or slightly superior efficacy compared to ABLC when tested against Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida krusei, Candida glabrata and Candida tropicalis. Effectiveness against C. glabrata was lower for ITZ (MIC(90) 2 microg/ml, and for ABLC, 0.5 microg/ml). For Aspergillus fumigatus, activity of ITZ was superior in comparison with ABLC (MIC(90) 1 and 16 microg/ml, respectively); MIC(90) for Aspergillus niger was 4 and 2 microg/ml for ABLC and ITZ, respectively. Scedosporium spp. showed a low susceptibility to both ABLC and ITZ. In conclusion, ABLC and ITZ are useful alternatives for the treatment of severe fungal infections. The selection of an antifungal agent should be made considering the toxicological and pharmacological properties and cost/benefit relationship and be supported by the susceptibility of the isolate.

Topics: Amphotericin B; Antifungal Agents; Culture Media; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Fungal; Fungi; Humans; Itraconazole; Microbial Sensitivity Tests; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Quality Control; Yeasts

Topics: Aged; Amphotericin B; Antifungal Agents; Chorioretinitis; DNA, Fungal; Drug Therapy, Combination; Drugs, Chinese Herbal; Eye Infections, Fungal; Female; Fluconazole; Fluorescein Angiography; Humans; Immunocompromised Host; Medicine, Chinese Traditional; Opportunistic Infections; Polymerase Chain Reaction; Prednisolone; Vitreous Body

Primary invasive mold infection of the oral cavity is a rare but serious complication in immunocompromised hosts. We report a case of fatal Trichoderma longibrachiatum stomatitis in a 66-year-old female patient with malignant lymphoma. The infection rapidly disseminated from the oral mucosa to the lungs during neutropenia. Despite intensive antifungal therapy with amphotericin B and itraconazole, there was a fatal progression of the condition. While Trichoderma species have been recognized to be pathogenic in profoundly immunosuppressed hosts, this is the first report of the primary oral focus causing a fatal infection.

Topics: Aged; Amphotericin B; Antifungal Agents; Disease Progression; Fatal Outcome; Female; Gingivitis, Necrotizing Ulcerative; Humans; Immunocompromised Host; Itraconazole; Lung Diseases, Fungal; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Mycoses; Neutropenia; Opportunistic Infections; Stomatitis; Trichoderma

Topics: Amphotericin B; Aspergillosis; Cause of Death; Humans; Lung Diseases, Fungal; Mycoses; Neoplasms; Opportunistic Infections

Rhinocerebral mucormycosis is a rare, fulminating opportunistic fungal infection caused by a fungus of the order mucorales. These fungi are ubiquitous, subsisting on decaying vegetation and diverse organic material. Although the fungi and spores of mucorales show minimal intrinsic pathogenicity towards normal persons, they can initiate aggressive and fulminating infection in the immune compromised host. Because rhinocerebral mucormycosis occurs infrequently it may pose a diagnostic and therapeutic dilemma for those who are not familiar with its clinical presentation. We present a patient with classical presentation of rhinocerebral mucormycosis involving the paranasal sinuses, the orbit and cranial base who, was treated by a combination of aggressive surgical and medical therapy and subsequently had surgical repair of the oral defect. The purpose of this presentation is to draw attention to the clinical presentation and pathogenesis of rhinocerebral mucormycosis and to emphasise the need for high index of suspicion in its diagnosis and management.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Debridement; Diabetes Mellitus, Type 2; Diagnosis, Differential; Facial Paralysis; Hemiplegia; Humans; Kenya; Male; Middle Aged; Mucormycosis; Nose Diseases; Opportunistic Infections; Orbital Diseases; Paranasal Sinus Diseases; Rare Diseases; Skull Base; Treatment Outcome

We established a reproducible lethal disseminated infection by the opportunistic fungus Scedosporium prolificans in an immunosuppressed murine model. We compared the effectiveness of the combined administration of liposomal amphotericin B (LAMB) and granulocyte colony-stimulating factor (G-CSF) with that of either agent alone and with that of amphotericin B deoxycholate (AMB). LAMB + G-CSF and LAMB treatments improved survival significantly with respect to the untreated control. The mean survival times of these three groups were 13.2, 9.1 and 7.9 days, respectively. Culture results in terms of colony counts for samples of deep organs were lower in mice treated with the combined therapy, although differences were not significant. Combined LAMB + G-CSF therapy could be a promising approach for the treatment of disseminated infections of S. prolificans, although further studies are required to determine the most appropriate doses.

Topics: Amphotericin B; Animals; Antifungal Agents; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppression Therapy; Liposomes; Male; Mice; Mice, Inbred Strains; Mycoses; Opportunistic Infections; Recombinant Proteins; Scedosporium; Survival Rate

Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Drug Resistance, Microbial; Fluconazole; Humans; Immunocompromised Host; Mycoses; Opportunistic Infections; Risk Factors

We report the successful outcome of allogeneic stem cell transplant (SCT) in a patient with acute lymphoblastic leukaemia (ALL) and pulmonary zygomycosis diagnosed prior to transplant. The lesion was surgically excised and SCT proceeded with antifungal therapy, granulocyte transfusions and G-CSF support during the period of neutropenia.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Lung Diseases, Fungal; Male; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome; Zygomycosis

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

Topics: Aged; Amphotericin B; Antiprotozoal Agents; Child, Preschool; Female; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Male; Opportunistic Infections

The NCCLS proposed standard M38-P describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds); however, standard conditions are not available for testing their fungicidal activities (minimum fungicidal or lethal concentrations [MFCs]). This study evaluated the in vitro fungistatic and fungicidal activities of voriconazole, itraconazole, and amphotericin B against 260 common and emerging molds (174 Aspergillus sp. isolates [five species], 23 Fusarium sp. isolates [three species], 6 Paecilomyces lilacinus isolates, 6 Rhizopus arrhizus isolates, 23 Scedosporium sp. isolates, 23 dematiaceous fungi, and 5 Trichoderma longibrachiatum isolates). MICs were determined by following the NCCLS M38-P broth microdilution method. MFCs were the lowest drug dilutions that resulted in fewer than three colonies. Voriconazole showed similar or better fungicidal activity (MFC at which 90% of isolates tested are killed [MFC(90)], 1 to 2 microg/ml) than the reference agents for Aspergillus spp. with the exception of Aspergillus terreus (MFC(90) of voriconazole and amphotericin B, >8 microg/ml). The voriconazole geometric mean (G mean) MFC for Scedosporium apiospermum was lower (2.52 microg/ml) than those of the other two agents (5.75 to 7.5 microg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for R. arrhizus were 2.1 to 2.2 microg/ml, but that for voriconazole was >8 microg/ml. Little or no fungicidal activity was shown for Fusarium spp. (2 to >8 microg/ml) and Scedosporium prolificans (>8 microg/ml) by the three agents, but voriconazole had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8 and 4 microg/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2.36 microg/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 microg/ml) for some Bipolaris spicifera and Dactylaria constricta var. gallopava. These data extend and corroborate the available fungicidal results for the three agents. The role of the MFC as a predictor of clinical outcome needs to be established in clinical trials by following standardized testing conditions for determination of these in vitro values.

Topics: Amphotericin B; Antifungal Agents; Fungi; Humans; Itraconazole; Microbial Sensitivity Tests; Mycoses; Opportunistic Infections; Pyrimidines; Triazoles; Voriconazole

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure

Aspergillus infection remains a major cause of morbidity and mortality after lung transplantation. Therefore, some strategies have been attempted, one of which is nebulized amphotericin B (nAB); however, the efficacy of this prophylaxis has not been shown clearly. The aim is to study whether nAB can protect against Aspergillus infection in lung transplant recipients.. A study of risk factors was conducted in 55 consecutive lung allograft recipients. Twenty-three potential risk factors were analyzed. In 44 (80%) patients, nAB was indicated as prophylaxis. Multivariate analysis using logistic regression was performed.. Eighteen of the 55 patients (33%) developed infection due to Aspergillus spp. Multivariate analysis showed nAB to be a preventive factor (odds ratio: 0.13; 95% confidence interval [CI] 0.02-0.69; p < 0.05) and cytomegalovirus (CMV) disease was an independent risk factor for developing Aspergillus infection (odds ratio: 5.1; 95% CI 1.35-19.17; p < 0.05). Only 1 patient required withdrawal of the prophylaxis owing to bronchospasm. nAB was well-tolerated in the remaining patients with only a few, mild, easily controlled side effects.. The present results show that nAB prophylaxis may be efficient and safe in preventing Aspergillus infection in lung-transplanted patients, and CMV disease increases the probability of Aspergillus infection.

Topics: Adolescent; Adult; Aerosols; Aged; Amphotericin B; Aspergillosis; Female; Humans; Lung Diseases, Fungal; Lung Transplantation; Male; Middle Aged; Nebulizers and Vaporizers; Opportunistic Infections; Risk Factors; Transplantation Immunology; Treatment Outcome

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Melphalan; Neoplasm Recurrence, Local; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisone; Procarbazine; Salvage Therapy; Skin; Transplantation, Homologous; Vinblastine; Vincristine

We report the occurrence of invasive aspergillosis (IA) in nonallografted patients with multiple myeloma (MM) who were treated at hematology or oncology centers in Europe during 1984-1996. Thirty-one cases met the criteria for definitive (21 [68%]) or probable (10 [32%]) IA. Of these cases, 23 (74%) were reported during 1992-1996. Twenty-nine cases (94%) occurred in patients with Durie-Salmon stage 3 MM, and 2 (6%) occurred in patients with Durie-Salmon stage 2 MM. The median time between MM and IA diagnoses was 8 months (range, 1-75 months). Sixteen patients (51%) had a neutrophil count

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Europe; Female; Humans; Itraconazole; Male; Middle Aged; Multiple Myeloma; Opportunistic Infections; Retrospective Studies; Transplantation, Homologous; Treatment Outcome

We report a case of endogenous aspergillus endophthalmitis. This infection occurred in a young immunocompromised boy of 6 years old. The localisation of the chorioretinitis was unusual because out of the posterior area. The evolution was favorable with recovering of the visual acuity under general treatment and intravitreous injections.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Child; Chorioretinitis; Diagnosis, Differential; Endophthalmitis; Humans; Injections; Male; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vitreous Body

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.

Topics: Amphotericin B; Antifungal Agents; Azoles; Blastomyces; Blastomycosis; Cost-Benefit Analysis; Female; Humans; Immunocompromised Host; Lung Diseases; Opportunistic Infections; Outcome Assessment, Health Care; Pregnancy; Pregnancy Complications, Infectious

Topics: Amphotericin B; Antifungal Agents; Child; Female; Fusarium; Humans; Immunocompromised Host; Lung Diseases, Fungal; Mycoses; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

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

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

Topics: Amphotericin B; Antifungal Agents; Drugs, Investigational; Humans; Immunocompromised Host; Mycoses; Opportunistic Infections; Randomized Controlled Trials as Topic; Triazoles

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

Invasive fungal infections after bone marrow transplantation have an extremely poor prognosis. Surgical excision in combination with antifungal therapy is considered necessary for treatment, especially for central nervous system (CNS) infection. We describe successful medical management with lipid complex amphotericin B (ABLC) and itraconazole, without surgical excision, of disseminated fungal infection involving the lungs and CNS in a patient with pancytopenia and graft-versus-host disease.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Drug Combinations; Drug Therapy, Combination; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Itraconazole; Lymphoma, Follicular; Male; Mucormycosis; Opportunistic Infections; Pancytopenia; Phosphatidylcholines; Phosphatidylglycerols

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

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

A retrospective review of 100 liver transplantations in 98 children was performed to determine the incidence of infection caused by Candida organism in these patients and to identify risk factors that may predispose to serious fungal infection. Thirty-one infections caused by Candida organisms developed during the initial 28 days posttransplantation: 19 were definite invasive infections (one deep site or one positive blood culture), 2 were probable invasive infections (three superficial sites), and 10 were urinary tract infections. Eleven of 19 patients had fungemia or a disseminated infection (two noncontiguous deep organs involved and/or positive blood cultures) and 8 of 19 had peritoneal candidiasis. Infection caused by Candida organisms was a contributing factor to mortality in 7 of 21 patients (case fatality rate of 33%) with invasive infection. Risk factors that were predictive for invasive infection by univariate analysis included the following: pretransplantation antibiotic therapy, length of transplant operation, transfusion requirement, number of days in the intensive care unit, number of days intubated, number of concurrent bacterial infections, number of antibiotics administered, number of laparotomies performed posttransplantation, retransplantation, hepatic artery thrombosis, bile leaks, and renal and respiratory failure. By logistic regression analysis, bile leak, hepatic artery thrombosis, preoperative steroid use, transfusion requirement, and the number of days intubated were identified as independent risk factors for invasive infection caused by Candida organisms. The use of prophylactic antifungal agents in high-risk patients may be important in reducing the serious morbidity and mortality associated with sepsis caused by Candida organisms in pediatric liver transplant recipients.

Topics: Adolescent; Alberta; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Candidiasis; Child; Child, Preschool; Female; Humans; Incidence; Infant; Liver Transplantation; Logistic Models; Male; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Risk Factors; Treatment Outcome

Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988-1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheterization, Peripheral; Cause of Death; Cephalosporins; Chemoprevention; Female; Fungemia; Humans; Itraconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Trichosporon

Fungal infections occur frequently in lung transplant patients, with the highest risk being in the early postoperative period (the initial hospitalization after lung transplantation). Aspergillus is responsible for more than half of all fungal infections, and Aspergillus has even been considered a contraindication for lung transplantation because of its difficult therapy and frequently fatal outcome. The aim of this article is to evaluate the success of an antifungal prophylaxis protocol to prevent fungal infection in the immediate postoperative period in lung transplant recipients.. From March 1994 to March 1997, we performed 52 lung transplants in 31 men and 21 women who received antifungal prophylaxis with fluconazole, 400 mg/d, and aerosolized amphotericin B, 0.6 mg/kg/d, during the postoperative period.. The mean (+/- SD) postoperative period duration was 49 +/- 27.5 days. No fungal infections were observed during this period, and all patients provided negative cultures. We also found no toxicity related to antifungal drugs. The dose of cyclosporine was easily adjusted in every recipient according to blood levels so that effective immunosuppression was not compromised.. In our study, the removal of the lungs and antifungal prophylaxis with fluconazole and aerosolized amphotericin B prevented fungal infection in the postoperative period in all 52 lung transplant recipients.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Female; Fluconazole; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Mycoses; Opportunistic Infections; Postoperative Period; Survival Rate

We report the case of a patient who, following surgical removal of an extensive tumour of the bowel, developed fungaemia. The yeast was isolated from repeated blood and urine cultures and identified as Rhodotorula rubra on the basis of macroscopic and microscopic features. Following treatment with amphotericin B, the patient's condition improved and the cultures became sterile.

Topics: Amphotericin B; Antifungal Agents; Fungemia; Humans; Immunocompromised Host; Intestinal Neoplasms; Male; Middle Aged; Mycoses; Opportunistic Infections; Postoperative Complications; Rhodotorula

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

Opportunistic fungal infection is a rare but severe complication in allogeneic bone marrow transplant (BMT) recipients. We report a 49-year-old patient who developed pneumonitis after BMT, due to a Mucorales fungus (class Zygomycetes), Absidia corymbifera. Infections due to mucormycosis are likely to become increasingly recognized even though the occurrence after BMT has only been described sporadically. We postulate that the patient was contaminated before BMT despite no intensive drug treatment or other iatrogenic features, related to his poor living conditions and developed the infection during aplasia. He immediately received i.v. liposomal amphotericin B (AmBisome) and GM-CSF. Because there was no response, the infected area and necrotic tissue were resected. Despite initial clinical and biological improvement and the absence of Mucor on mycological examination post-surgery, the patient died 3 weeks later from bilateral pulmonary infection and multiorgan failure.

Topics: Absidia; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Fatal Outcome; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Multiple Organ Failure; Necrosis; Opportunistic Infections; Postoperative Complications; Transplantation, Homologous

Meta-analyses may become biased if the reported data in the individual trials are biased and if overlap among trials cannot be identified. We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia. In 3 large trials that comprised 43% of the patients identified for the meta-analysis, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is recognized as an ineffective drug in these circumstances, this approach creates a bias in favor of fluconazole. Furthermore, 79% of the patients were randomized to receive oral amphotericin B, which is poorly absorbed and not an established treatment, in contrast to intravenous amphotericin B, which was administered in 4 of 5 placebo-controlled trials, or 86% of patients. It was unclear whether there was overlap among the "polyene" trials, and it is possible that results from single-center trials were included in multicenter trial reports. We were unable to obtain information to clarify these issues from the trial authors or the manufacturer of fluconazole. Two of 11 responding authors replied that the data were with the drug manufacturer and two indicated that they did not have access to their data because of change of affiliation. In the meta-analyses, fluconazole and amphotericin B (mostly given orally) had similar effects (13 trials), whereas nystatin was no better than placebo (3 trials). Since individual trials are rarely conclusive, investigators, institutions, and pharmaceutical companies should provide essential details about their work to ensure that meta-analyses can accurately reflect the studies conducted and that patients will realize maximum benefits from treatments. We recommend that investigators keep copies of their trial data to help facilitate accurate and unbiased meta-analyses.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Humans; Meta-Analysis as Topic; Mycoses; Neoplasms; Neutropenia; Nystatin; Opportunistic Infections; Publication Bias; Randomized Controlled Trials as Topic; Research Design

Topics: Amphotericin B; Antifungal Agents; Child; Cytarabine; Female; Fusarium; Hematologic Neoplasms; Humans; Mycoses; Neutropenia; Opportunistic Infections

The objective of this study was to evaluate the effects of itraconazole as a first choice drug in the treatment of pulmonary aspergillosis in heart transplant recipients. Heart transplant recipients suffering from invasive pulmonary aspergillosis were included in this study. Group 1 included 4 patients treated with i.v. itraconazole (Janssen Pharmaceutica) 400 mg daily, as a first choice drug for 28 d. Itraconazole was discontinued and amphotericin-B was started before the 28th day if clinical or radiographic worsening was observed. Group 2 included 3 patients treated with amphotericin-B as a first choice drug. Itraconazole was discontinued in all patients of Group 1 after 12-26 d of treatment because of radiographic worsening (n = 3) or combined clinical and radiographic worsening (n = 1). Subsequent treatment with amphotericin-B resulted in improvement of all patients. On a 5-yr follow-up period no relapse of aspergillosis was observed in 3 of them. The fourth patient expired from cerebral hemorrhage. The 3 patients of Group 2 treated with amphotericin-B showed a gradual improvement, and all were doing well on a 2-yr follow-up. In conclusion, in our study population consisted of heart transplant recipients amphotericin-B was superior to itraconazole in the treatment of invasive pulmonary aspergillosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Heart Transplantation; Humans; Itraconazole; Lung Diseases, Fungal; Microbial Sensitivity Tests; Middle Aged; Opportunistic Infections; Radiography

We report two cases of cryptococcosis in patients with Waldenstrom's macroglobulinaemia and chronic lymphocytic leukaemia that responded to prolonged therapy with systemic amphotericin and flucytosine. Cryptococcosis, although more common in those with impaired cell mediated immunity, should also be considered as a complication in patients with impaired antibody responses.

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Female; Flucytosine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Opportunistic Infections; Waldenstrom Macroglobulinemia

Mucormycosis is an opportunistic infection occurring in the severely immunocompromised patient. A case of mucormycosis occurring in a patient who sustained an 85 per cent TBSA burn injury is reported. Diagnosis and management is reported in the paper.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Body Surface Area; Burns; Debridement; Drug Therapy, Combination; Female; Flucytosine; Humans; Immunocompromised Host; Injections, Intravenous; Mucormycosis; Opportunistic Infections; Rhizopus; Wound Infection

Topics: Amphotericin B; Antifungal Agents; Humans; Immunosuppressive Agents; Itraconazole; Kidney Transplantation; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Osteomyelitis; Sphenoid Sinusitis; Tomography, X-Ray

Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or immunosuppressed patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are required for cure, causing significant renal toxicity. Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals, Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which results in significant reduction of toxicity, especially nephrotoxicity. We describe three patients with life-threatening rhinocerebral mucormycosis treated with ABCD. All patients had high serum creatinine levels due to prior treatment with amphotericin B; these levels reverted to normal during treatment with ABCD. Two patients with diabetes mellitus were cured after receiving a combination of surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome, had an initial good response, with cure of the fungal infection; however, he eventually died of his primary illness. To the best of our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with ABCD.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Female; Humans; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Paranasal Sinus Diseases

Topics: Adult; Amphotericin B; Antifungal Agents; Cholangitis, Sclerosing; Female; Histoplasmosis; Humans; Immunocompromised Host; Liver Transplantation; Opportunistic Infections

Purulent pericarditis caused by Candida species is rare and is associated with very high mortality. Immunosuppressed transplant patients are particularly susceptible to fungal infections. We report a case of Candida purulent constrictive pericarditis in an immunocompromised heart transplant patient who was treated successfully with antifungal agents, surgical drainage, and pericardiectomy.

Topics: Amphotericin B; Anti-Infective Agents; Antifungal Agents; Candidiasis; Ciprofloxacin; Disease Susceptibility; Drainage; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppression Therapy; Male; Middle Aged; Opportunistic Infections; Pericardiectomy; Pericarditis, Constrictive; Pleural Effusion; Pseudomonas aeruginosa; Pseudomonas Infections; Suppuration

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has been observed only in immunocompromised persons. An unusual case of autochthonous disseminated histoplasmosis in a 22-year-old Spanish man who had been treated with azathioprine and prednisone for 4 weeks before admission is reported. The development of an acute form of the disease may represent an endogenous reactivation of a latent infection as a complication of immunosuppression resulting from the use of these drugs. This case illustrates the potential risk of this opportunistic fungal infection in patients receiving azathioprine therapy, an association that has been rarely described before.

Topics: Adult; Amphotericin B; Antifungal Agents; Azathioprine; Bone Marrow Cells; Drug Carriers; Drug Therapy, Combination; Histoplasma; Histoplasmosis; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liposomes; Lymph Nodes; Male; Opportunistic Infections; Prednisone

A 24-year-old female diabetic patient was hospitalized because of ketoacidosis and a necrotic wound on the hand. Debridement and antibiotic therapy failed to halt the process. After demonstration of Mucor in cultures from the wound, the patient underwent extensive surgery and amphotericin B was administered. When the necrotic process continued despite these measures, adjunctive hyperbaric oxygen (100% O2 at 2.5 ATA for 90 minutes) was administered daily for a total of 21 treatment sessions. She gradually improved, and at 2 months follow-up most of the wound had healed. Although the mortality rate of cutaneous/soft-tissue zygomycosis is markedly lower than that of the rhinocerebral form, morbidity is still considerably high. Successful use of hyperbaric oxygen has been reported in rhinocerebral zygomycosis, and it may have been of benefit in this high-risk patient by preventing local and systemic spreading of the fungus. This report is the first case of the use of hyperbaric oxygen for cutaneous/soft-tissue zygomycosis. It is suggested that hyperbaric oxygen be considered for this indication in diabetic patients as an adjunct to surgery and amphotericin B.

Topics: Adult; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Debridement; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Fingers; Humans; Mucormycosis; Opportunistic Infections; Soft Tissue Infections

A 39-year-old woman with systemic lupus erythematosus suffered a prolonged neurological illness associated with very low levels of glucose in her cerebrospinal fluid (CSF). Six months later, and after numerous CSF investigations, Histoplasma capsulatum was cultured. To our knowledge, this is the first report of cerebral histoplasmosis in Australia in a patient who is not HIV positive.

Topics: Adult; Amphotericin B; Antifungal Agents; Blood Glucose; Brain; Drug Therapy, Combination; Female; Histoplasmosis; Humans; Itraconazole; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Meningitis, Fungal; Neurologic Examination; Opportunistic Infections

No comparative clinical information on the properties of lipid-associated amphotericin preparations is presently available. In this single-centre retrospective analysis over a 5-year period the indications, efficacy and toxicity of true liposomal amphotericin (AmBisome) were compared with a lipid complexed preparation (Abelcet). In a novel approach APACHE III scores were used in addition to neutrophil counts, disease status and additional immunosuppression to accurately assess the severity of illness in both groups and enable valid comparison. Overall, AmBisome at a median dose of 1.9 mg/kg/d was found to have similar clinical outcome to Abelcet at a median dose of 4.8 mg/kg/d. Nephrotoxicity and electrolyte abnormalities were similar in both groups. Rigors and febrile episodes were more common with Abelcet. Prospective randomized comparative trials are required to clarify the optimum dosages and therapeutic and economic issues associated with these agents.

Topics: Adult; Amphotericin B; Antifungal Agents; Creatinine; Drug Combinations; Female; Hematologic Neoplasms; Humans; Immune Tolerance; Leukocyte Count; Male; Mycoses; Neutrophils; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies; Treatment Outcome; Water-Electrolyte Imbalance

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Brain Abscess; Drug Carriers; Follow-Up Studies; Humans; Kidney Transplantation; Liposomes; Magnetic Resonance Imaging; Male; Middle Aged; Opportunistic Infections; Safety

The EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches.. All members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period.. One hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1-21. Acute myeloid leukaemia (AML) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients with diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%)-amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99).. IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Female; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Survival Analysis

Amphotericin B treatment in oncological patients is irrepaceable due to the high frequency of mycotic infections. From data in the literature ensues that the most serious undesirable effect of amphotericin B is nephrotoxicity, manifested by a reduced glomerular filtration and impaired tubular function (in particular the development of hypokalemia, and hypomagnesaemia). Prophylaxis of nephrotoxicity is despite major efforts unsatisfactory. In the submitted work the authors tested in a major group of patients their working hypothesis based on previous observations, that prophylactic replacement of the increasing ion losses in urine during amphotericin B treatment without waiting for a decline of serum concentrations of these ions, along with adequate hydration delays or eliminates the decline of glomerular functions.. During amphotericin B therapy of 25 oncological patients renal functions, Na, K and Mg urinary excretion and the serum concentrations of these ions were followed up in detail. The urinary losses were replaced. No overall prophylaxis to prevent acute toxic reactions associated with administration of the drug was used. The mean dose of amphotericin B was 0.82 mg/kg, the mean diuresis 3662 ml/24 hours. Acute toxic reactions calling for hydrocortisone administration were observed only in 6% of the patients. During treatment the urinary K and Mg losses increased significantly and had to one replaced. There was also a significant increase of the excretory fractions of K and Na. However there were no significant changes of serum ions nor a rise of creatinine. The creatinine clearance even increased slightly though insignificantly (1.384 ml/s as compared with 1.392 ml/s).. Consequential hydration of patients and prophylactic replacement of urinary ion losses during amphotericin B therapy are effective in preventing ion disbalances and a decline of glomerular functions. Acute toxic reactions associated with administration of amphotericin B are infrequent.

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney; Mycoses; Neoplasms; Opportunistic Infections

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

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

The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Neoplasms; HIV Infections; Humans; Itraconazole; Logistic Models; Male; Middle Aged; Multivariate Analysis; Opportunistic Infections; Prognosis; Prospective Studies; Risk Factors; Survival Analysis

Rhinocerebral mucormycosis is recognized as a potentially aggressive and commonly fatal fungal infection. The classic presentation is involvement of nasal mucosa with invasion of the paranasal sinuses and orbit. Mucormycosis is most commonly seen in association with diabetic ketoacidosis, but disease demographics have changed with the onset of AIDS and the advent of powerful immunosuppressive drugs. Treatment includes aggressive debridement, systemic antifungal therapy, and control of underlying comorbid factors. Although surgical intervention remains essential, advances in medical therapy have permitted a more limited surgical approach to minimize functional loss without compromising survival. We present the UCLA experience with rhinocerebral mucormycosis from 1955 to 1995, with emphasis on the evolution of disease presentation and alternative treatment options.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brain Diseases; Child; Combined Modality Therapy; Debridement; Diabetic Ketoacidosis; Female; Follow-Up Studies; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Mucormycosis; Nasal Mucosa; Nose Diseases; Opportunistic Infections; Orbital Diseases; Paranasal Sinus Diseases; Retrospective Studies; Survival Rate; Treatment Outcome

We present a case of disseminated intracranial infection by Candida albicans in a 5-year-old girl who had fever and a change of consciousness after surgery for complex congenital heart malformation. MR imaging revealed multiple small ring-enhancing hemorrhagic abscesses. One year after antifungal treatment, the abscesses and ventriculomegaly were almost completely resolved. The patient was discharged in a stable but vegetative condition.

Topics: Amphotericin B; Antifungal Agents; Brain; Candidiasis; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluconazole; Heart Defects, Congenital; Humans; Hydrocephalus; Meningitis, Fungal; Opportunistic Infections; Postoperative Complications; Ventriculoperitoneal Shunt

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Fatal Outcome; Humans; Liver Cirrhosis; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Subdural Effusion; Tomography, X-Ray Computed

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Fusarium; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Mycoses; Opportunistic Infections

Children acquire blastomycosis, with rare exceptions, through the respiratory route. Nearly half of those who are infected may be asymptomatic. Cough is the most common symptom and is usually without sputum production, and hemoptysis is not noted. Other symptoms are chest pain (described as tightness or pain when breathing), weight loss, night sweats, and loss of appetite. The severity of illness is variable and may simulate an upper respiratory infection, bronchitis, pleuritis, or pneumonia. As in adults, an overwhelming infection may cause respiratory failure even in immunocompetent children and in immunocompromised children who live in or travel to endemic areas are susceptible to infection. Some reports based on consecutive cases note extrapulmonary dissemination commonly in children, whereas dissemination is rarely noted in outbreak cases. Chronicity of the disease favors extrapulmonary dissemination. Chest radiograph patterns are alveolar infiltrates, consolidation, and nodule(s), and these may be accompanied by cavitation. Diagnosis is suspected when the symptoms that mimic common respiratory infections persist for more than 2 weeks and by a history of residence or travel to an endemic area. Chest radiographic findings of nodule(s) or cavitation further increase the suspicion. Confirmation of diagnosis is by microscopic examination and culture of sputum. When expectorated sputum is unavailable, bronchoscopy with lavage and biopsy or percutaneous needle biopsy of lung is the appropriate next step. Disease that is progressive or severe or disseminated to other organs should be treated. Amphotericin B is effective and results in excellent cure rates. Experience using oral azoles is limited in children.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Biopsy; Blastomycosis; Bronchoscopy; Child; Female; Humans; Lung; Lung Diseases, Fungal; Male; Opportunistic Infections; Risk Factors

We report on the case of a 25-year-old female with severe systemic lupus erythematosus (SLE) who presented with pancytopenia, fever, arthralgia and abdominal pain. After antibiotic treatment, the patient was afebrile for 3 days before her temperature rose again. Dyspnoea and cough pointed towards pneumonia which was confirmed by X-ray. Different antibiotics and the antimycotic agent fluconazol were given. The lupus flare was treated with high-dose prednisolone. After a couple of days, the dyspnoea increased and mechanical ventilation became necessary. Bronchoscopy and transbronchial biopsy revealed the diagnosis of invasive aspergilloses. Despite of an immediate treatment with amphotericin B, the patient died because of respiratory insufficiency. The literature on aspergillosis in SLE is reviewed and prophylactic, diagnostic and therapeutic options are discussed for this infectious complication which has an 80% mortality in patients with SLE.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Fatal Outcome; Female; Humans; Lupus Erythematosus, Systemic; Opportunistic Infections

Topics: Adult; Amphotericin B; Antifungal Agents; Debridement; Drug Therapy, Combination; Hepatitis C; Humans; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Mucormycosis; Opportunistic Infections; Postoperative Complications

Necrotizing myofascial fungal infections of the upper extremity is a rare event even in immunocompromised hosts. We report the course of a renal transplant patient who developed extensive necrotizing myofascial infection of an upper extremity secondary to Histoplasma capsulatum. Initial, functional, upper limb salvage was achieved after aggressive surgical debridement and high doses of amphotericin B. The patient ultimately succumbed to systemic fungal sepsis. The etiology and treatment of these infections are discussed.

Topics: Amphotericin B; Combined Modality Therapy; Debridement; Fasciitis; Fatal Outcome; Forearm; Histoplasmosis; Humans; Kidney Transplantation; Male; Middle Aged; Myositis; Necrosis; Opportunistic Infections; Postoperative Complications

Histoplasmosis, an opportunistic fungal infection endemic in the Ohio and Mississippi river valleys, is caused by a dimorphic fungus Histoplasma capsulatum. Most infections are asymptomatic or self-limited febrile illness. Immunosuppressed renal transplant recipients are susceptible to a disseminated disease. We report 5 cases of disseminated histoplasmosis seen in our institute over a period of 25 years amongst 1074 renal transplant recipients. The duration of immunosuppression prior to the diagnosis of infection ranged from 84 days to 14 years. All patients had pulmonary involvement. Three patients received an antilymphocyte preparation and 1 patent received intravenous pulse steroids in the 3 months prior to the onset of infection. Histopathologic examination of the involved organ(s) provided rapid diagnostic information allowing early treatment with amphotericin B. All infections resolved with no relapses to date. In conclusion immunosuppressed patients are more prone to disseminated histoplasmosis. Early recognition and prompt treatment with amphotericin B resolved the infection without relapse.

Topics: Adult; Amphotericin B; Antifungal Agents; Antilymphocyte Serum; Disease Susceptibility; Female; Glucocorticoids; Histoplasma; Histoplasmosis; Humans; Immunosuppression Therapy; Itraconazole; Kidney Transplantation; Lung Diseases, Fungal; Male; Middle Aged; Ohio; Opportunistic Infections; Transplantation, Homologous

A 71 year old man with newly diagnosed acute myelomonocytic leukaemia developed a soft tissue infection of his foot during his first course of chemotherapy. Scedosporium apiospermum was isolated from the lesion, which resolved rapidly on treatment with intravenous amphotericin B despite being resistant in vitro to this agent. This observation suggests that sensitivity testing of S apiospermum should be interpreted with caution and that clinical response may be a better indicator of outcome.

Topics: Aged; Amphotericin B; Antifungal Agents; Drug Resistance; Foot Dermatoses; Humans; Leukemia, Myelomonocytic, Acute; Male; Mycetoma; Opportunistic Infections; Pseudallescheria

Mucormycosis usually occurs in immunocompromised patients or in patients with diabetes mellitus. Pathogens are moulds of the mucorales species. The diagnosis is made by histological examination of biopsies. A 39 year-old patient with insulin-dependent diabetes mellitus was admitted with a tentative diagnosis of a tumour of the maxilla. After diagnosis of hyphae of the mucorales species, the patient's diabetes was stabilised and he was treated over 17 weeks with amphotericin B (40 mg per day) and made a good recovery. A 58 year-old insulin-dependent patient with ethmoidali and sphenoidali sinusitis did not respond to antibiotic therapy. Mucormycosis was diagnosed by means of biopsy. Although treatment with amphotericin B was started, the patient died after 3 weeks due to multiple organ failure.

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fatal Outcome; Humans; Male; Middle Aged; Mucormycosis; Opportunistic Infections; Paranasal Sinuses; Sinusitis

We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections. Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage. Both patients had had severe abdominal involvement during the acute PCM disease. Immunological evaluation showed cellular and humoral immunity impairment. Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other. The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine. Both patients had a good response to treatment with complete regression of the lesions. They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection. PCM also did not reactivate. The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C. neoformans infections of AIDS and transplant patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections; Paracoccidioidomycosis

A cell-free growth medium for the opportunistic pathogenic ameba Balamuthia mandrillaris is presented. This represents an advance over the use of monkey kidney cells for growth of the amebas and can be helpful in isolation of these amebas from brain tissue from cases in which amebic meningoencephalitis is a diagnostic possibility, as well as for biochemical and molecular biological studies. Three isolates of Balamuthia have been cultured in this medium. The cell-free growth system was also used to screen cultures for sensitivity to a variety of antimicrobial agents. Of the various drugs tested, pentamidine isethionate was most effective against amebas (ca. 90% inhibition after 6 days of exposure), but the drug was amebastatic and not amebacidal in the axenic system at the highest concentration tested (10 micrograms/ml).

Topics: Amebiasis; Amoeba; Amphotericin B; Animals; Antiprotozoal Agents; Benzamidines; Cell-Free System; Culture Media; Drug Resistance; Humans; Meningoencephalitis; Microbial Sensitivity Tests; Opportunistic Infections; Pentamidine

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

To describe the MR appearance of necrotizing fungal granulomas occurring in the liver of leukemic patients with hepatosplenic fungal disease and transfusional hemosiderosis on antifungal antibiotics.. Four patients with acute myelogenous leukemia (n = 2) or acute lymphocytic leukemia (n = 2) who developed hepatosplenic fungal disease, and were treated with antifungal medication, underwent MRI examination on a 1.5 T MR imager. MR images were prospectively evaluated and correlated with liver biopsy (three patients), and clinical picture (one patient).. Multiple liver lesions measuring approximately 1 cm in diameter were identified in all patients. Lesions possessed a distinctive MR appearance: central mild hyperintensity with a peripheral ring of very low signal intensity on precontrast T1- and T2-weighted images. The central region of the lesions enhanced following gadolinium administration with the peripheral ring remaining low in signal intensity.. Necrotizing fungal granulomas in the liver of patients with transfusional hemosiderosis on treatment with antifungal antibiotics have a distinctive appearance of moderate high signal intensity center on T1- and T2-weighted and postgadolinium MR images with a peripheral rim of low signal intensity. This appearance reflects the presence of iron-laden macrophages in the periphery of granulomas and may be expected in processes that initiate an immune response involving aggregation of macrophages in the liver of patients with transfusional iron overload.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Candidiasis; Child; Female; Granuloma; Hemosiderosis; Humans; Itraconazole; Leukemia; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Opportunistic Infections; Transfusion Reaction

Topics: Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Dermatomycoses; Fusarium; Humans; Immunocompromised Host; Male; Opportunistic Infections; Postoperative Complications

We describe six children with acute decreases in heart rate temporally related to amphotericin B administration. All patients had achieved their maximal dose within 3 to 4 days. Heart-rate drops occurred as early as day 3 but could be delayed up to day 7 after start of therapy. The mean heart rate dropped from 104 +/- 8/min (range 96 to 114) to 62 +/- 8/min (range 48 to 72) (P = 0.0001). A slower heart rate than baseline was noted during the entire duration of drug administration, from 60 minutes of starting the infusion to 220 minutes (mean 120 +/- 40) after discontinuation of the infusion. This reaction was noted in six of 90 (6.7%) patients who had amphotericin. These six children were compared with six age-matched children who received the drug but in whom such changes in heart rate did not develop. The method of administration of amphotericin B was similar in both patients and controls, starting with 0.25 mg/kg/day and increasing by 0.25 mg/kg/day up to 1 mg/kg/day. Children with heart-rate drop received amphotericin for 4.6 +/- 1.8 days, significantly shorter than their controls (12.6 +/- 6.9 days) (P = 0.02), suggesting that this adverse effect has led to early discontinuation of amphotericin therapy. Physicians and nurses caring for children receiving amphotericin B should be aware of this potential adverse effect, which can be serious in a patient with an underlying heart condition or in a patient who is already on heart-rate-lowering drugs.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Case-Control Studies; Child; Child, Preschool; Female; Heart Rate; Humans; Male; Opportunistic Infections

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5% (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5% (n = 10), 7.2% (n = 11) and 2.6% (n = 4), respectively. Mortality associated with systemic fungal infections was 80% (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.

Topics: Adult; Amphotericin B; Analysis of Variance; Antifungal Agents; Female; Fungemia; Humans; Incidence; Liver Transplantation; Logistic Models; Male; Middle Aged; Mycoses; Opportunistic Infections; Retrospective Studies; Risk Factors

We describe a patient with chronic granulomatous disease who presented with erythematous papular skin lesions on the chest, back, and arm. Examination of biopsy specimens from the lesions on the arm and back showed suppurative granulomata in association with acute and chronic inflammation. Histopathologic examination of a specimen from the lesion on the arm revealed fungal elements, and cultures yielded Microascus cinereus. The patient was treated with 2.5 g of intravenous amphotericin B, and the lesions resolved. We report what is, to our knowledge, the first case of invasive disease due solely to M. cinereus.

Topics: Amphotericin B; Ascomycota; Child; Dermatomycoses; Female; Granuloma; Granulomatous Disease, Chronic; Humans; Opportunistic Infections

Topics: Acremonium; Amphotericin B; Bone Marrow Transplantation; Female; Gastrointestinal Diseases; Humans; Infant; Mycoses; Opportunistic Infections; Severe Combined Immunodeficiency

Most cases of mucormycosis occur in immunosuppressed children. Intracranial extension is lethal and must be prevented with early specific treatment.. A 42 month-old boy was admitted suffering from acute lymphoblastic leukemia. Edema of the left eyelid developed on the sixth day of induction chemotherapy. Mucormycosis was suspected because of gradual extension of infection to nasal ala and periorbital area with fever, edema of nasal turbinates and nasal black secretions. Chemotherapy was discontinued and the patient was given intravenous amphotericin B (1.0 mg/kg/day) and heparin associated with G.CSF. Improvement was only temporary and scan examination performed on day 17 showed involvement of the orbit, eye and wall of the maxillary sinus; cultures of secretions were positive for staphylococcus and Absidia corymbifera. Remission of leukemia was obtained a few days later permitting surgical resection of involved tissues on day 30. A relapse of mucormycosis was observed six weeks later despite prolonged administration of amphotericin B requiring extended resection of necrotic areas and replacement of amphotericin B by its liposomal form (Ambisome). Bone marrow relapse of leukemia required further chemotherapy. The patient is in good condition 30 months after the initial symptoms.. Our patient seems to be the first with prolonged remission of facial mucormycosis and acute leukemia despite relapse of both diseases. This favorable outcome could be due to the use of Ambisome.

Topics: Amphotericin B; Child, Preschool; Humans; Injections, Intravenous; Male; Mucormycosis; Opportunistic Infections; Orbital Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sinusitis

60 patients undergoing bone marrow or stem cell transplantation were treated with liposomal Amphotericin-B for documented or suspected mycosis. 34 patients had a prior course of conventional Amphotericin-B with the following adverse effects: increasing creatinine above 1.4 mg/dl (n = 17), increasing creatinine below 1.5 mg/dl (n = 9), no response (n = 6), and clinical side-effects (n = 4). Liposomal Amphotericin-B failed in 6/7 patients with culture-proven mycosis who died from infection with Aspergillus (n = 2) and Candida (n = 4), respectively. One patient with Candida lambica sepsis was cured. No patient with clinically or serologically suspected or diagnosed infection died from mycosis. Liposomal Amphotericin-B was well tolerated in 57 patients, even after side-effects of the conventional formulation. Adverse effects occurred in three cases, requiring the withdrawal of the drug in one patient. Due to toxic side-effects of the high-dose therapy and transplant-related complications, it was difficult to evaluate the influence of liposomal Amphotericin-B on laboratory parameters. Eight patients showed a decrease of creatinine levels, which had increased above normal values under preceding therapy with conventional Amphotericin-B. Liposomal Amphotericin-B is well tolerated in patients undergoing high-dose therapy and bone marrow transplantation. The efficacy of liposomal Amphotericin-B needs to be investigated in randomized studies in comparison with conventional Amphotericin-B.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Treatment Outcome

Pulmonary mucormycosis associated with hematologic malignancy is an uncommon, but important opportunistic fungal pneumonia that is usually a fatal infection. Only a few survivors of pulmonary mucormycosis have been reported.. A case report of invasive thoracopulmonary mucormycosis during remission-induction therapy for acute lymphoblastic leukemia and a review of the literature are presented.. The fungal lesions extended to both lungs, the left ribs, and intercostal muscles. Percutaneous needle biopsy and immunostaining of the fungal hyphae established the diagnosis of thoracopulmonary mucormycosis. The patient was treated with granulocyte-colony stimulating factor (G-CSF) and intravenous amphotericin B for 9 weeks and the lesions in the right lung disappeared. Left pneumonectomy and partial resection of the chest wall were later performed. The left lung was grossly necrotic and contained a large cavity and bronchopulmonary fistula. Thereafter, antileukemic therapy was resumed and completed without recurrence of mucormycosis or leukemia.. In the management of mucormycosis, the addition of G-CSF to the conventional treatment may substantially improve outcome.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Female; Granulocyte Colony-Stimulating Factor; Humans; Lung Diseases, Fungal; Mucormycosis; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thoracic Diseases; Tomography, X-Ray Computed

We describe here a case of cryptococcal empyema thoracis and periauricular pyogenic abscess in a child with Bruton's agammaglobulinaemia. The cryptococcal empyema thoracis was treated with intravenous amphotericin B and intravenous fluconazole for six weeks followed by oral fluconazole. The pyogenic periauricular abscess was surgically drained and treated with intravenous ceftazidime and cloxacillin for two weeks. He also received monthly intravenous immunoglobulin.

Topics: Abscess; Agammaglobulinemia; Amphotericin B; Ceftazidime; Child, Preschool; Cloxacillin; Combined Modality Therapy; Cryptococcosis; Empyema, Pleural; Fluconazole; Humans; Immunization, Passive; Male; Opportunistic Infections; Otitis Externa

Mucormycosis is a rare fungal infection that has been described mainly in oncologic and diabetic patients. We here report the cases of two leukaemic patients in whom pulmonary mucormycosis was diagnosed. Prompt diagnosis, therapy with amphotericin B and surgery when possible, are the cornerstones in the treatment of this fungal infection. Although infrequent, this infection must be suspected in oncohaematological patients with lung infiltrates.

Topics: Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Itraconazole; Leukemia, Promyelocytic, Acute; Lung Diseases, Fungal; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Mucormycosis; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Liposomal amphotericin B (AmBisome) was used for suspected or confirmed fungal infection complicating 133 neutropenic episodes in 116 patients not tolerating, or not responding to, conventional amphotericin. Adverse effects were infrequent and no significant renal impairment resulted. Acute reactions occurred in five patients, reversible hepatic dysfunction in 23, and hypernatraemia in 17. The putative mycosis resolved with AmBisome treatment in 81 episodes (61%) and progressed with fatal outcome in 25 (19%), but the diagnosis was equivocal in most, and in 27 episodes (20%) evidence indicating nonfungal pathogenesis emerged. Treatment efficacy is, however, evaluable in those with proven aspergillosis. 13/17 patients with confirmed invasive aspergillosis responded to AmBisome (77%), conventional amphotericin having failed in 11. Treatment was successfully discontinued when the neutrophil count was < 1 x 10(9)/l in eight responders (61%). In four further patients treated for suspected aspergillosis, disseminated infection was documented at post-mortem, but the true incidence is unknown. This analysis confirms that AmBisome is well tolerated and effective against invasive mycoses in neutropenic patients, and may salvage patients when conventional amphotericin proves excessively toxic or ineffective.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Agents; Aspergillosis; Candidiasis; Child; Drug Carriers; Female; Humans; Liposomes; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies

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

Topics: Adolescent; Amphotericin B; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Mucormycosis; Opportunistic Infections; Postoperative Period

The usual management of opportunistic fusarium infection in the immunocompromized patient is with systemic antifungals, despite which little impact is made on the mortality which approaches 100%. We describe a case of fusarium infection of the foot in a bone marrow transplant recipient which was successfully managed with local wide excisional surgery and intravenous liposomal amphotericin B.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Combined Modality Therapy; Dermatomycoses; Foot Dermatoses; Fusarium; Humans; Male; Opportunistic Infections

Candida endophthalmitis may occur either during systemic Candida infection (candidemia), particularly in immunocompromised hosts or as a single manifestation in drug abusers.. One case of endogenous candida endophthalmitis (ECE) in a patient with systemic candidiasis and four cases of drug abusers are presented. Well confined inflammatory lesions in retina and choroid were adequately treated with systemic Amphotericin B administration, whereas lesion extension beyond the internal limiting membrane towards the vitreous required surgical management, to remove epiretinal fibrovascular tissue, and intravitreal Amphotericin B injection.. In all cases, treatment resulted to regression of the lesions, however visual function recovery depends on location of chorioretinal lesions.

Topics: Adult; Amphotericin B; Candidiasis; Chorioretinitis; Combined Modality Therapy; Dose-Response Relationship, Drug; Endophthalmitis; Female; Humans; Injections, Intravenous; Male; Middle Aged; Opportunistic Infections; Vitrectomy

A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. D-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, D-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits.

Topics: Agranulocytosis; Amphotericin B; Animals; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Biomarkers; Bronchoalveolar Lavage Fluid; Ergosterol; Galactose; Kidney Diseases; Life Tables; Liposomes; Lung Diseases; Mannans; Mannitol; Opportunistic Infections; Rabbits; Survival Analysis

Three children who developed pulmonary aspergillosis while being treated for leukaemia or non-Hodgkin's lymphoma. Each child continued with intensive myelosuppressive chemotherapy regimens during the infection and each was successfully treated with antifungal prophylaxis based on itraconazole by mouth. Amphotericin B was also given during periods of severe neutropenia. No reactivation of the fungal infection was seen.

Topics: Amphotericin B; Antineoplastic Agents; Aspergillosis; Child, Preschool; Drug Therapy, Combination; Humans; Itraconazole; Lung; Lung Diseases, Fungal; Male; Neutropenia; Opportunistic Infections; Radiography

To identify risk factors that might predict for systemic fungal infections in marrow transplant recipients within the first 100 days and to assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia and infection with invasive Aspergillus species in patients at risk.. A retrospective analysis of transplant outcomes for 331 allogeneic marrow recipients transplanted between 1983 and 1989 was performed to identify patients who might be at increased risk of fungal infection. Factors analyzed included disease, remission status, transplant regimen, graft-versus-host disease (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3 months posttransplant was begun in 1987 to evaluate its utility in reducing systemic mycoses.. There were 18 episodes of candidemia and 18 systemic mycoses documented by blood or tissue culture or by biopsy. The initiation of high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD prophylaxis in 1986 was identified as the most important risk factor for fungal infections, with a sixfold increase in infections as compared with the previous GVHD regimen (P < .0001); this was despite a significant decrease in the incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced the incidence of fungal infections from 30% to 9% (P = .01) without renal toxicity. Cyclosporine levels were lower in the patients who received amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02). Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II to IV GVHD (P = .01) were also identified as risk factors for fungal infection.. Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.

Topics: Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Child; Child, Preschool; Cyclosporine; Female; Humans; Incidence; Infant; Male; Middle Aged; Mycoses; Opportunistic Infections; Predictive Value of Tests; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome

Rhinocerebral aspergillosis (RA) is becoming increasingly common in patients undergoing bone marrow transplantation (BMT). The disease can involve nearly all major head and neck structures, including the nose, paranasal sinuses, and orbits. Intracranial extension of the infection is of major concern, since this is usually a fatal complication. Our study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eight patients (1.9%) developed RA, 5 of whom had underlying hematologic malignancies, and 3 of whom had severe aplastic anemia. Only 2 of the 8 patients responded completely to therapy, with a follow-up of 15 months. It appears that RA is a fatal complication in immunocompromised patients post-BMT. Early diagnosis followed by extensive surgical debridement of necrotic tissue and systemic, as well as topical, antifungal therapy with amphotericin B or its new formulations and the patient's recovery of bone marrow function may improve the outcome of this life-threatening complication.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus flavus; Bone Marrow Transplantation; Brain Diseases; Female; Humans; Infant; Male; Middle Aged; Opportunistic Infections; Paranasal Sinus Diseases; Retrospective Studies; Treatment Outcome

Efficacy of immunoglobulin G (IgG) bearing liposomal amphotericin B (LAMB-IgG), liposomal amphotericin B without IgG (LAMB) or free amphotericin B (fAMB/Fungizone) was investigated in the treatment of systemic candidiasis in a neutropenic mouse model. Treatment with a single dose (0.6 or 0.9 mg amphotericin B per kg body weight) of LAMB-IgG resulted in a significant increase in the survival rate of neutropenic mice infected with 3 x 10(5) cfu of Candida albicans compared to untreated controls, mice injected with IgG, or liposome alone. Survival was also better in neutropenic mice treated with LAMB-IgG than in neutropenic mice treated with the same dose of LAMB or fAMB. Moreover, 65% of all mice survived the infection after treatment with a single dose of 0.6 mg AMB of the LAMB-IgG formulation. Quantitative culture counts of organs showed that both fAMB and LAMB-IgG formulations even at a dose of 0.3 mg AMB/kg, cleared C. albicans from the spleens, livers, and lungs but not from the kidneys. However, a decreased number of C. albicans cells was recovered from the kidneys of mice that survived the infection. Results of the study suggest that LAMB-IgG is more effective than LAMB or fAMB in the therapy of disseminated candidiasis in neutropenic mice.

Topics: Amphotericin B; Animals; Candidiasis; Combined Modality Therapy; Drug Evaluation, Preclinical; Evaluation Studies as Topic; Female; Immunoglobulin G; Liposomes; Mice; Neutropenia; Opportunistic Infections

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Coccidioidomycosis; Female; Humans; Leukemia, Promyelocytic, Acute; Lung Diseases, Fungal; Male; Middle Aged; Multiple Myeloma; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus; Child; Child, Preschool; Cross Infection; Dermatomycoses; Female; Hospitals, Pediatric; Hospitals, University; Humans; Immunocompromised Host; Infant, Newborn; Lung Diseases, Fungal; Male; Ontario; Opportunistic Infections; Retrospective Studies

Inhaled amphotericin was administered to 29 patients with prolonged neutropenia and toxicity was analyzed. Treatment consisted of 30 mg of amphotericin B administered by nebulizer once daily via either a hand-held nebulizer or face mask. The mean duration of treatment was 16 days. Toxicity was minimal and patient had significant toxic reaction to the inhaled medication. This study documents that nebulized amphotericin B has less than 10% incidence of severe toxicity with 95% confidence level. Guidelines for future trials and use are suggested.

Topics: Administration, Inhalation; Adult; Amphotericin B; Humans; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Pneumonia

Candida sepsis is a very serious complication in severely burned patients. This mainly affects patients whose immune system is weakened by illness and/or by drugs. Often diagnosis is difficult because candida sepsis occurs after an initial infection, but therapy is always difficult. Good fungicidal drugs are available, but their side effects limit their effectivity. Two severely burned patients who were suffering from a gram-negative sepsis confirmed by clinical and laboratory data developed candida sepsis. Conventional therapy failed, and both patients suffered from renal failure with constantly high candida-latex-antigen titre. By means of the liposomal encapsulated amphotericin B, which has the same fungicidal effect as amphotericin B, but without its limiting side effects, both, patients could be saved. The kidneys functioned as normal again, the laboratory findings were normal when the patients were discharged.

Topics: Adult; Amphotericin B; Burns; Candidiasis; Drug Carriers; Humans; Liposomes; Male; Middle Aged; Opportunistic Infections

Topics: Adolescent; Amphotericin B; Candidiasis; Female; Humans; Immunocompromised Host; Infusions, Intravenous; Liver Abscess; Opportunistic Infections; Portal Vein; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Amphotericin B; Antifungal Agents; Drug Interactions; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Mycoses; Opportunistic Infections

From June 1990 to August 1991, 21 patients infected with the human immunodeficiency virus (HIV) presented with systemic mycosis caused by Penicillium marneffei. Between August 1987 and August 1991, only five patients were observed who had P. marneffei infection but not HIV infection. The clinical presentation included fever, cough, and generalized papular skin lesions. For 11 of these 21 patients, the presumptive diagnosis of P. marneffei infection could be made by microscopic examination of Wright's-stained bone marrow aspirate and/or touch smears of skin specimens obtained by biopsy several days before the results of culture were available. Initial clinical response to treatment with either parenteral amphotericin B or oral itraconazole was favorable in most patients. Epidemiological and clinical evidence suggest that this systemic mycosis is caused by an important opportunistic pathogen and that it should be included in the differential diagnosis of AIDS, at least for countries in areas of endemicity, i.e., Southeast Asia and China.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; HIV Infections; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Mycoses; Opportunistic Infections; Penicillium; Retrospective Studies; Thailand; Treatment Outcome

Candida species are important nosocomial pathogens; however, little is known about the epidemiology of Candida lusitaniae, an organism frequently resistant to amphotericin B. We evaluated 98 patients admitted to the bone marrow transplant and medical intensive care units of a tertiary-care hospital. Each patient with C. lusitaniae was matched with control patients. Restriction fragment analysis of DNA was used to determine strain relatedness. Seven patients (7.1%) with C. lusitaniae were identified; five acquired C. lusitaniae after admission to the study unit. All isolates were susceptible to amphotericin B. There were no differences between patients and controls with regard to duration of stay in the study unit, antibiotic administration, antifungal therapy, immunosuppressive therapy, catheter use, or underlying disease. Temporal and geographic clustering of five patients with identical strains occurred. No common source was identified. Restriction fragment analysis revealed a total of eight strains, and five patients shared one strain type. These results demonstrate exogenous acquisition of C. lusitaniae. The mechanism of acquisition is probably indirect contact transmission between patients.

Topics: Adult; Aged; Amphotericin B; Bone Marrow Transplantation; Candida; Candidiasis; Cross Infection; DNA, Fungal; Drug Resistance, Microbial; Epidemiologic Methods; Female; Humans; Intensive Care Units; Male; Michigan; Middle Aged; Opportunistic Infections; Polymorphism, Restriction Fragment Length

Between June 1988 and May 1991 88 orthotopic liver transplants and 1 liver and pancreas transplant were performed at the Liver Transplantation Department of the Ospedale Maggiore of Milan. All the patients underwent mycological surveillance and received antifungal prophylaxis with oral amphotericin B (6000 mg/day) or oral or intravenous fluconazole (200 mg/day) from the time of their transplant. The incidence of Candida colonization was 67%. Fluconazole was superior to oral amphotericin B in the treatment of C. albicans colonization (9/9 vs 6/15), but less effective in the treatment of colonization by other Candida spp. (0/3 vs 3/3). Deep-seated candidiasis developed in 5 patients, caused by C. albicans in 4 cases and C. krusei in 1. C. albicans infection resolved rapidly with fluconazole in 2 subjects, with intravenous amphotericin B alone in 1, and with amphotericin B plus flucytosine in the other. On the contrary, C. krusei infection did not respond to treatment with amphotericin B combined with flucytosine. Aspergillosis was diagnosed in 11 patients, of whom 4 died from invasive aspergillosis, despite 15 and 26 days of amphotericin B treatment in 2. In another patient invasive aspergillosis, diagnosed a few hours before retransplantation, improved with liposomal amphotericin B, but this man died from cytomegalovirus infection one month later. Aspergillosis was eradicated by itraconazole in 4 other patients and by topical amphotericin B in 2 whose infection was localized to surgical wound.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Candidiasis; Child; Child, Preschool; Fluconazole; Humans; Infant; Liver Transplantation; Male; Opportunistic Infections; Pancreas Transplantation; Premedication

We report the treatment of cerebral aspergillosis with amphotericin B, flucytosine, surgery, and liposomal amphotericin B (L-AmB) after a liver transplant. The patient died 2 months after cessation of antifungal therapy, as a consequence of multiple-system organ failure. The only relevant postmortem finding in the brain was a small, encapsulated abscess containing hyphae. This case indicates that L-AmB is an effective alternative drug for cerebral aspergillosis.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Brain Diseases; Combined Modality Therapy; Flucytosine; Humans; Liver Transplantation; Male; Middle Aged; Opportunistic Infections

Cryptococcosis is more frequently observed since the appearance of the acquired immunodeficiency syndrome (AIDS). AIDS has modified the clinical and evolutive forms of the disease. This study reviews the changes produced in the infection from the context of AIDS.. The present is a retrospective study (1985-1990) including patients presenting: 1) a positive latex agglutination test (serum or spinal fluid) or 2) a Sabouraud culture positive for cryptococcus. Clinical histories were revised collecting clinical, radiologic, analytic, therapeutic and evolutive data.. Twenty-six patients (21 males) were included in the study. Twenty patients had the human immunodeficiency virus. The clinical picture was: 22 cases with cryptococcal meningitis (13 with hematogenous participation), 3 with pulmonary cryptococcosis and one with disseminated cryptococcosis without meningeal involvement. The patients with AIDS had: greater frequency of positive hemocultures, higher serologic titers and fewer with the meningeal syndrome. The number of T4 lymphocytes was lower than 150 elements/ml in AIDS patients. In 17 patients treatment with amphotericin B and 5-fluorocytosine was administered, 5 received amphotericin B and two fluconazole and two did not receive the above since they had not been diagnosed alive. There were 6 deaths and 10 relapses in 6 AIDS patients and none in the remaining patients.. The incidence of cryptococcosis has increased as a consequence of AIDS. In these patients the disease occurs in advanced stages of immunodeficiency and frequently in disseminated, severe and paucisymptomatic forms. Treatment is usually effective although a maintenance therapy is required to avoid relapse.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Aged, 80 and over; Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus; Female; Flucytosine; Humans; Male; Middle Aged; Opportunistic Infections; Retrospective Studies

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Flucytosine; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections; Prognosis; Retrospective Studies; Treatment Outcome

We discuss 19 cases of infection due to Cryptococcus neoformans diagnosed in 438 AIDS patients admitted to our center (4%). Fourteen of them showed meningitis confirmed by culture of C. neoformans in CSF. Clinical features were rather unspecific and disorders in CSF parameters were non striking. The diagnostic techniques performed with best results were culture of C. neoformans and antigen determination, especially in serum. Survival probability at one year was 75%. Treatment response was good. Treatment with fluocytosine did not seem to provide additional benefits versus amphotericin alone, neither in respect to clinical evolution nor regarding survival probability at one year. Fluconazole has shown effectiveness in maintenance therapy, being not be possible to evaluate it as an acute phase therapy because the low number of cases in which it was studied. It is advisable to follow a suppressive treatment, having found a 10% relapse rate in patients following therapy and a 50% in those who interrupted it.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; HIV-1; Homosexuality; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Opportunistic Infections; Substance Abuse, Intravenous

Low-dose methotrexate sodium therapy used for nonmalignant disease has been associated with a variety of opportunistic infections with pathogens occurring in patients with defective cellular immunity. This article describes the unusual development of disseminated histoplasmosis as a probable complication of immunosuppression resulting from use of methotrexate.. We report the cases of three patients in whom disseminated histoplasmosis developed while receiving low-dose methotrexate therapy for psoriasis. Disease manifestations were unusually severe in two of the three patients. All three cases were disseminated, and two cases resulted in illnesses requiring intensive medical treatment. Each patient responded appropriately to antifungal treatment, although one patient has required long-term suppressive treatment because of persistent Histoplasma antigenuria. These cases illustrate the risk for opportunistic fungal infections in patients receiving low-dose methotrexate therapy for nonmalignant diseases.. Histoplasma should be added to the list of pathogens to be suspected in patients receiving such therapy.

Topics: Acute Disease; Adult; Amphotericin B; Female; Histoplasmosis; Humans; Immunity, Cellular; Male; Methotrexate; Opportunistic Infections; Psoriasis; Time Factors

In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants.. To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990.. The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro.. In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Candidiasis; Drug Therapy, Combination; Fluconazole; Humans; Leukemia; Mycoses; Opportunistic Infections; Postoperative Complications; Retrospective Studies

A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding. Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus. Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis. Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily. The clinical, microbiological and serological findings regressed after 4 weeks. After 8 weeks the creatinine concentration rose to 2.5 mg/dl. Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g. He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily. The cryptococcal antigen titre had fallen to normal within one year. The prophylactic regimen has been continued now for three years without recurrence or other fungal infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antigens, Bacterial; Cryptococcus; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis, Cryptococcal; Opportunistic Infections; Recurrence; Time Factors; Zidovudine

These patients demonstrate the difficulty in arriving at the diagnosis of disseminated histoplasmosis. The diagnosis in two of the three patients also served as the initial AIDS case-defining opportunistic infection. In each of these patients, the clinical presentations were atypical and in only one patient was a positive exposure history elicited. Recurrent bowel obstruction was the presenting complaint in the first patient and the diagnosis was made only on pathologic exam of the resected small bowel. The second patient's diagnosis was made on biopsy of the colon via colonoscopy. The third patient's diagnosis also eluded an extensive FUO workup; he was diagnosed by bone marrow culture and silver stain of a mediastinal lymph node biopsy, despite serial negative serologic tests for histoplasmosis. The first two patients had significant gastrointestinal disease which is a relatively unusual manifestation for disseminated histoplasmosis. The third patient illustrates the limited diagnostic usefulness of serologic testing in AIDS patients and the continued usefulness of bone marrow analysis in an FUO evaluation. In conclusion, these case presentations demonstrate that disseminated histoplasmosis in patients with HIV infection can present with unusual manifestations, outside of the typical endemic arca, without a positive exposure history or positive serologic test, and may be the initial AIDS case-defining opportunistic infection in these patients. Consequently, a disseminated histoplasmosis should be considered in all AIDS patients with perplexing clinical presentations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Amphotericin B; Female; Histoplasma; Histoplasmosis; Humans; Ketoconazole; Male; Maryland; Middle Aged; Opportunistic Infections

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

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

Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Female; Humans; Male; Middle Aged; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Female; Humans; Latin America; Opportunistic Infections; Paracoccidioidomycosis

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Esophagitis; Female; Fluconazole; Ganciclovir; Humans; Infusions, Intravenous; Ketoconazole; Male; Opportunistic Infections; Prospective Studies; Treatment Outcome

Topics: Adult; Amphotericin B; Humans; Immunosuppression Therapy; Liver Transplantation; Mycoses; Opportunistic Infections; Retrospective Studies; Risk Factors

A 60-year-old man receiving chemotherapy for an intermediate-grade non-Hodgkin's lymphoma developed multiple papuloerythematous cutaneous lesions. Alternaria alternata was cultured from the lesions, and hyphae were seen in biopsy specimens. This is an unusual infection, without a well-established treatment, in patients with lymphoma. The use of amphotericin B resulted in cure.

Topics: Alternaria; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Dermatomycoses; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Clindamycin; Communicable Diseases; Fluconazole; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: Adult; Amphotericin B; Blastomyces; Blastomycosis; Diabetes Mellitus, Type 1; HIV Infections; Homosexuality; Humans; Lung Diseases, Fungal; Male; Opportunistic Infections

Immediately after induction therapy for acute lymphoblastic leukemia, a 2 1/2-year-old child developed invasive pulmonary aspergillosis revealed by pneumothorax, an unusual manifestation. Despite treatment with amphotericin B, status epilepticus occurred; this manifestation was related to diffuse ischemic cerebral lesions probably caused by cerebral aspergillosis. Outcome was fatal. Early invasive pulmonary aspergillosis is responsible for non-specific pneumonia. Thoracic CT scan and fiberoptic bronchoscopy are informative investigations. At recovery of bone marrow aplasia, the occurrence of hemoptysis and the discovery of excavated lesions on roentgenograms are suggestive of the diagnosis. Cerebral aspergillosis should be routinely considered whenever neurologic symptoms develop in a patient with agranulocytosis, fever, and pneumonia. The prognosis of invasive aspergillosis depends above all on the promptness of treatment; amphotericin B should be given intravenously whenever broad spectrum antimicrobial therapy fails to induce apyrexia in a patient with agranulocytosis.

Topics: Amphotericin B; Aspergillosis; Brain Diseases; Child, Preschool; Female; Humans; Lung Diseases, Fungal; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis

We have presented a case of a stable diabetic outpatient who had an acute illness that proved to be Torulopsis glabrata fungemia responsive to amphotericin B therapy. Her only apparent additional predisposition was a nonobstructing renal calculus. Fungemia with this organism in an outpatient is most unusual. T glabrata should be an additional consideration in outpatient as well as inpatient illnesses, especially in diabetic women.

Topics: Amphotericin B; Candidiasis; Diabetes Mellitus, Type 2; Female; Humans; Kidney Calculi; Middle Aged; Opportunistic Infections

Trichosporon beigelii (Trichosporon cutaneum) was identified as the causative agent of chronic meningitis in a 15-year-old boy with acute lymphocytic leukaemia. After a neutropenic episode following cytostatic treatment and itraconazole therapy as prophylaxis, cerebrospinal fluid (CSF) samples yielded growth of Trichosporon beigelii. Treatment with amphotericin B, flucytosine and high doses of fluconazole was followed by clinical improvement, although CSF pleocytosis remained. The cross-reactivity between Cryptococcus neoformans and Trichosporon beigelii in a cryptococcal antigen latex test was used as a means of diagnosis in CSF and serum samples.

Topics: Adolescent; Amphotericin B; Chronic Disease; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Male; Meningitis; Mycoses; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporon

Topics: Administration, Oral; Amphotericin B; Child; Cryptococcosis; Female; Fluconazole; Humans; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Recurrence

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

Thrombocytopenia is a rare side effect of amphotericin B. Two patients with acute leukaemia in remission who developed severe thrombocytopenia during amphotericin B therapy are reported. Thrombocytopenia recovered after the withdrawal of the drug in one patient and after reducing the dose in the other patient.

Topics: Adult; Amphotericin B; Aspergillosis; Bronchopneumonia; Female; Humans; Lung Diseases, Fungal; Male; Opportunistic Infections; Thrombocytopenia

The AIDS epidemic has made previously uncommon infectious diseases and tumors commonplace in HIV-infected individuals. In this article we discuss specific cases of various infections and tumors of the sinonasal tract. Several of these diseases may be the presenting signs of HIV-seropositivity and AIDS. As a result, the clinician first to see such patients must be aware of the diagnosis of these diseases and tumors so that proper testing and treatment may ensue.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-Bacterial Agents; HIV Seropositivity; Humans; Ketoconazole; Nasopharyngeal Diseases; Opportunistic Infections; Paranasal Sinus Diseases; Rifampin; Therapeutic Irrigation

Disseminated histoplasmosis is an increasingly important opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS). We report the first case of histoplasmosis as a cause of pleural effusion in a patient with AIDS. Recognition of the typical intracellular yeast on a Wright-Giemsa stained smear of the pleural fluid cells allowed prompt initiation of amphotericin B.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasma; Histoplasmosis; Humans; Male; Opportunistic Infections; Pleural Effusion

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Disease; Heart Transplantation; Humans; Immunosuppression Therapy; Itraconazole; Ketoconazole; Male; Neoplasms; Opportunistic Infections

An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9-136 days), and mean cumulative dose per patient was 1117 mg (range, 231-7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level greater than or equal to 2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Glomerular Filtration Rate; Humans; Kidney; Leukemia; Middle Aged; Neoplasms; Opportunistic Infections; Saline Solution, Hypertonic

The clinical and histopathological features and the therapeutic response of a pustular eruption occurring in a homosexual man with Acquired Immune Deficiency Syndrome (AIDS) is reported. The rare cutaneous presentation consisted of mostly circumscribed, tender, tense pustules, associated with erythema, confined to the face and neck. Biopsy of these lesions revealed intracellular round to oval bodies surrounded by a clear space, consistent with Histoplasma capsulatum. Prompt resolution was observed after initiation of amphotericin B therapy. Clinicians are alerted to the occurrence of exotic presentations of this entity and emphasis is given to the need for skin biopsy and culture to avoid delay in diagnosis and failure to initiate appropriate therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Histoplasmosis; Humans; Male; Opportunistic Infections

Candida antigen latex agglutination testing was performed twice weekly during 217 admissions of 200 patients undergoing intensive chemotherapy alone or supported by autologous or allogeneic bone marrow transplantation. Eleven patients developed invasive candidiasis, three of whom survived; 6 (54.5%) of the 11 had positive Candida antigens. In 206 admissions, invasive candidiasis could not be documented. Of the 60 patients who died, 41 underwent autopsy examination, and 29 (71%) had positive Candida antigens. The latex test was also positive in 30 (20.5%) of the survivors and 10 (53%) of the unautopsied patients. Serum creatinine levels were greater than 2 mg/dL in 61% and 13% of patients with positive and negative Candida antigens, respectively (P less than .0001). For patients in whom the presence or absence of invasive candidiasis could be unequivocally demonstrated, the sensitivity, specificity, and positive and negative predictive values of the latex test at a titer of 1:4 were 54.5%, 29%, 17%, and 70.5%, respectively, suggesting that the latex test should not be used to diagnose invasive candidiasis in immunocompromised patients.

Topics: Amphotericin B; Antigens, Fungal; Bone Marrow Transplantation; Candidiasis; Creatinine; Humans; Immunosuppression Therapy; Latex Fixation Tests; Opportunistic Infections

Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis.. Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens.. High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse.. In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antigens, Fungal; Blood; Histoplasma; Histoplasmosis; Humans; Opportunistic Infections; Polysaccharides; Radioimmunoassay; Recurrence

To assess the efficacy and toxicity of long-term maintenance amphotericin B therapy in preventing relapses after treatment in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis.. Open, nonrandomized pilot study.. Three private, university-affiliated community hospitals.. We studied 22 consecutive patients with disseminated histoplasmosis and human immunodeficiency virus (HIV) infection. Sixteen patients completed the study, 5 patients died before completing the initial intensive phase of treatment, and 1 patient received a different treatment regimen.. Seven patients were treated with an initial intensive course of 1000 mg of amphotericin B, followed by weekly infusions of 50 to 80 mg until a cumulative dose of 2000 mg was attained; biweekly infusions of 50 to 80 mg were then continued indefinitely. Nine patients received an initial amphotericin B course of 2000 mg followed by weekly infusions of 80 mg.. Of the 7 patients in the 1000-mg intensive regimen group, 6 patients have survived without clinical or laboratory evidence of a histoplasmosis relapse, and 1 died of unrelated causes. Of the 9 patients in the 2000-mg intensive regimen group, 7 patients have survived, 1 patient died of a histoplasmosis relapse, and 1 patient died of other causes. Thus, 13 of 14 patients (93%) who did not die of other causes remained relapse-free. The median follow-up period was 14 months (range, 2 to 23 months). No apparent differences in outcome were observed between patients treated with weekly maintenance regimens and those treated with biweekly maintenance regimens. Sixty-three percent of patients developed intravascular device-related complications.. Long-term, intermittent maintenance amphotericin B therapy in HIV-infected patients with disseminated histoplasmosis is well tolerated and is highly effective in suppressing relapses after treatment.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Catheters, Indwelling; Drug Administration Schedule; Female; Histoplasmosis; Humans; Male; Middle Aged; Opportunistic Infections; Pilot Projects; Recurrence

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male; Nervous System Diseases; Opportunistic Infections

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Female; Humans; Immune Tolerance; Leukemia, Lymphocytic, Chronic, B-Cell; Lung Diseases, Fungal; Middle Aged; Opportunistic Infections

Topics: Abscess; Adrenal Gland Diseases; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Diagnosis, Differential; Drainage; Drug Therapy, Combination; Humans; Ketoconazole; Male; Middle Aged; Opportunistic Infections; Rifampin; Sarcoidosis

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Opportunistic Infections

Topics: Amphotericin B; Antifungal Agents; Drug Interactions; Flucytosine; Humans; Ketoconazole; Mycoses; Opportunistic Infections

Topics: Amphotericin B; Humans; Infusions, Parenteral; Mycoses; Opportunistic Infections

The efficacy of fluconazole, a new bis-triazole antifungal agent, was compared with that of orally administered ketoconazole and parenterally administered amphotericin B against aspergillus and cryptococcus infections in mice. Fluconazole was 5-20-fold more active than ketoconazole against systemic aspergillosis and against systemic, intracranial and pulmonary cryptococcosis but was less active than amphotericin B.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Brain Diseases; Cryptococcosis; Female; Fluconazole; Ketoconazole; Lung Diseases, Fungal; Mice; Opportunistic Infections; Triazoles

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Humans; Immune Tolerance; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mitosporic Fungi; Mycoses; Opportunistic Infections; Remission Induction

Invasive sinonasal aspergillosis is a severe and frequently fatal infection in immunosuppressed patients with hematologic malignancies. Seven patients with sinonasal aspergillosis who failed to respond to conventional amphotericin B (AmpB) were treated with liposomal AmpB (L-AmpB).AmpB was incorporated into multilamellar vesicles consisting of dimyristoyl phosphatidyl-choline and dimyristoyl phosphatidylglycerol in a 7:3 molar ratio. Five patients had underlying hematologic malignancies, one patient had aplastic anemia, and one patient had no underlying disease. All patients had biopsy-proven invasive Aspergillus sinusitis, and had failed conventional antifungal therapy including AmpB. Five patients were cured and two did not respond to treatment. Fever and chills were infrequent and, when they occurred, mild, and responded well to conventional management. No severe renal or central nervous system toxicity was observed. L-AmpB is effective and less toxic than conventional AmpB in the treatment of invasive Aspergillus sinusitis.

Topics: Amphotericin B; Aspergillosis; Drug Evaluation; Humans; Leukemia; Liposomes; Methods; Opportunistic Infections; Sinusitis; Time Factors

Immunosuppressed burned patients receiving antibiotics for suppression of bacterial infection are ideal hosts for opportunistic fungi. Massive excision of burns with autograft and homograft coverage has radically changed the course of disease. Three hundred ninety-three patients were admitted to the Shriners Burns Institute, of whom 125 patients had fungus cultured during their hospitalization and 42 patients subsequently developed involvement of three or more organs. Twenty-one of the 42 patients developed Candida septicemia requiring amphotericin B or flucytosine therapy. The mean third-degree burn in patients with Candida septicemia was 65% total body surface area compared to three-organ involvement/no clinical sepsis at 38% mean third-degree burn. Patients developing candidemia did so during the first week postburn and 7 days after excision therapy. It is hypothesized that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. With early recognition of burn wound invasion by routine biopsies, wound swabs, and early amphotericin therapy, the mortality has been reduced to 14% compared to 60-90% reported in other series.

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Burns; Candidiasis; Child; Flucytosine; Humans; Immune Tolerance; Opportunistic Infections; Retrospective Studies; Wound Infection

Topics: Amphotericin B; Candidiasis; Child; Child, Preschool; Drug Therapy, Combination; Female; Flucytosine; Humans; Immune Tolerance; Opportunistic Infections; Urinary Tract Infections

Fungemia caused by Trichosporon beigelii (cutaneum) has been recently recognized as a fatal infection afflicting immunocompromised patients. The authors report the case of a leukemic patient who developed splenic infection from disseminated T. beigelii. Treatment with amphotericin B, 5-fluorocytosine, and splenectomy proved successful. The etiology of disseminated T. beigelii infection, visceral seeding, and combination antifungal therapy also are discussed.

Topics: Adult; Amphotericin B; Combined Modality Therapy; Flucytosine; Humans; Leukemia, Monocytic, Acute; Male; Mycoses; Opportunistic Infections; Splenectomy; Trichosporon