amphotericin-b and Cystic-Fibrosis

The genus Blastobotrys consists of at least 20 species. Disease in humans has been reported with B adeninivorans, B raffinosifermentans, B proliferans and B serpentis, mostly in immunocompromised patients and those with cystic fibrosis.. We report a lung infection secondary to B raffinosifermentans in a cystic fibrosis patient successfully treated with isavuconazole and review the literature of invasive infections caused this genus. We also evaluated clinical isolates in our laboratory for species identification and antifungal susceptibility.. Phylogenetic analysis was performed on a collection of 22 Blastobotrys isolates in our reference laboratory, and antifungal susceptibility patterns were determined for nine clinically available antifungals against 19 of these isolates.. By phylogenetic analysis, 21 of the 22 isolates in our collection were identified as B raffinosifermentans and only 1 as B adeninivorans. Most were cultured from the respiratory tract, although others were recovered from other sources, including CSF and blood. Isavuconazole, caspofungin and micafungin demonstrated the most potent in vitro activity, followed by amphotericin B. In contrast, fluconazole demonstrated poor activity. The patient in this case responded to isavuconazole treatment for breakthrough infection due to B raffinosifermentans that was cultured from pleural fluid while on posaconazole prophylaxis post-bilateral lung transplantation for cystic fibrosis.. Blastobotrys species are rare causes of infections in humans and primarily occur in immunocompromised hosts. In our collection, the majority of isolates were identified as B raffinosifermentans. To our knowledge, this is the first report of successful treatment of such an infection with isavuconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Cystic Fibrosis; Female; Fluconazole; Genes, Fungal; Humans; Immunosuppression Therapy; Microbial Sensitivity Tests; Mycoses; Nitriles; Phylogeny; Pneumonia; Pyridines; Saccharomycetales; Triazoles

Aspergillus fumigatus is the most frequent filamentous fungus isolated from respiratory specimens from patients with cystic fibrosis (CF). Triazoles are the most widely used antifungals in the treatment of allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis (IA) in CF patients. Treatment success could be severely compromised by the occurrence of azole-resistant A. fumigatus (ARAf), which is increasingly reported worldwide from both clinical samples and the environment. In previous studies, ARAf has been detected in up to 8% of CF patients. Isolates from CF patients requiring antifungal treatment should therefore be routinely subjected to antifungal susceptibility testing. The optimal treatment of ABPA or IA in CF patients with azole-resistant isolates has not been established; treatment options include liposomal amphotericin B i.v. and/or echinocandins i.v.

Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Azoles; Cystic Fibrosis; Drug Resistance, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests; Pulmonary Aspergillosis

To review the data available in literature about nebulized amphotericin B (AMB) in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) and to report our experience in the use of this drug, with a particular therapeutic scheme.. We used nebulized liposomal amphotericin B (L-AMB) in a patient affected by CF, complicated by ABPA. The previous combined treatment with oral steroids and azoles had no respiratory benefit and caused relevant side effects. Amphotericin B has always been well tolerated and permitted a slight steroid tapering. We also observed benefits in pulmonary function and laboratory tests.. Few data are available in literature about the use of nebulized AMB in CF and there are no RCTs evaluating antifungals in CF-ABPA. In our opinion, the reported case suggests that nebulized L-AMB could represent a possible strategy in ABPA management in CF patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Disease Management; Humans; Male; Young Adult

Bronchiectasis is a pathologic bronchial dilatation with loss of function that can result from multiple inflammatory and infectious injuries to the conducting airways of the lung. Molds, particularly the filamentous fungus Aspergillus fumigatus, have been implicated as a common cause of both cystic fibrosis (CF) and non-CF bronchiectasis, the latter primarily in patients with severe asthma. The pathogenesis of mold-associated bronchiectasis is usually due to atopic sensitization to mold allergens in the presence of active chronic endobronchial fungal infection with host innate and adaptive immune deviation to a Th2-dominated inflammation, a condition known as allergic bronchopulmonary aspergillosis (ABPA) (or allergic bronchopulmonary mycosis if a non-Aspergillus mold is implicated). Diagnostic criteria of ABPA continue to evolve, while treatment relies upon downregulation of the allergic inflammatory response with immunomodulatory agents and antifungal pharmacotherapy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchiectasis; Cystic Fibrosis; Humans; Hypersensitivity; Immunoglobulin E; Triazoles

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Topics: Administration, Inhalation; Amikacin; Amphotericin B; Anti-Bacterial Agents; Aztreonam; Ceftazidime; Colistin; Cystic Fibrosis; Gentamicins; Humans; Nebulizers and Vaporizers; Respiratory Tract Infections; Tobramycin

Topics: Amphotericin B; Anti-Bacterial Agents; Anti-Ulcer Agents; Cimetidine; Colistin; Cystic Fibrosis; Humans; Receptors, Drug; Virus Diseases

Topics: Administration, Inhalation; Aerosols; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antiprotozoal Agents; Chronic Disease; Cystic Fibrosis; Drug Resistance, Microbial; Forecasting; Humans; Immunocompromised Host; Respiratory Tract Infections

In cystic fibrosis (CF) patients, fungal colonization of the respiratory tract is frequently found. Aspergillus fumigatus, Scedosporium genus, and Exophiala dermatitidis are the most commonly isolated moulds from the respiratory tract secretions of CF patients. The aim of this 5-year surveillance study was to identify trends in species distribution and susceptibility patterns of 212 mould strains identified as Aspergillus spp., Scedosporium spp., and Exophiala spp., isolated from sputum of 63 CF patients who received long-term therapy with itraconazole (ITR) and/or voriconazole (VRC). The Aspergillus isolates were identified as members of the sections Fumigati (n = 130), Flavi (n = 22), Terrei (n = 20), Nigri (n = 8), Nidulantes (n = 1), and Usti (n = 1). Among the 16 species of the genus Scedosporium, 9 were S. apiospermum, 3 S. aurantiacum, and 4 S. boydii. Among the 14 Exophiala species, all were molecularly identified as E. dermatitidis. Overall, 94% (15/16) of Scedosporium spp., 50% (7/14) of E. dermatitidis, and 7.7% (14/182) of Aspergillus spp. strains showed high MIC values (≥8 µg/ml) for at least one antifungal. Particularly, 8.9% (19/212) of isolates showed high MIC values for amphotericin B, 11.7% (25/212) for ITR, 4.2% (9/212) for VRC, and 3.3% (7/212) for posaconazole. In some cases, such as some A. fumigatus and E. dermatitidis isolates recovered from the same patient, susceptibility to antifungal azoles decreased over time. We show that the use of azoles for a long time in CF patients causes the selection/isolation of mould strains with higher MIC values.. The use of azoles for a long time in cystic fibrosis patients causes the selection/isolation of Aspergillus, Scedosporium, and Exophiala species with higher MIC values.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillus; Azoles; Cystic Fibrosis; Exophiala; Itraconazole; Scedosporium; Triazoles; Voriconazole

Approximately 10% of people with cystic fibrosis (CF) have mutations that result in little to no CFTR production and thus cannot benefit from CFTR modulators. We previously found that Amphotericin B (AmB), a small molecule that forms anion channels, restored HCO. To determine whether AmB can impact physiology in people with CF, we first tested whether Fungizone, a clinically approved AmB formulation, could cause electrophysiological effects consistent with anion secretion in primary cultures of CF airway epithelia. We then evaluated the capacity of AmB to change nasal potential difference (NPD), a key clinical biomarker, in people with CF not on CFTR modulators.. AmB increased transepithelial Cl. Our results provide the first evidence that AmB can impact a clinical biomarker in people with CF. These results encourage additional clinical studies in people with CF to determine whether small molecule anion channels can provide benefit.

Topics: Administration, Intranasal; Amphotericin B; Antifungal Agents; Cells, Cultured; Codon, Nonsense; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Respiratory Mucosa; Voltage-Dependent Anion Channels

This review is the second article in the State-of-the-Art series and aims to evaluate medications used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in pediatric and adult patients with cystic fibrosis (CF). ABPA is one of several organisms that are found in the airways of CF patients. This review provides an evidence-based summary of pharmacokinetic (PK)/pharmacodynamic (PD), tolerability, and efficacy studies of medications including corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, and voriconazole), and a monoclonal antibody omalizumab in the treatment of ABPA and identifies areas where further study is warranted.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Amphotericin B; Anti-Infective Agents; Antibodies, Monoclonal; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Child; Cystic Fibrosis; Female; Humans; Itraconazole; Omalizumab; Voriconazole

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO

Topics: Amphotericin B; Animals; Bicarbonates; Cells, Cultured; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Epithelium; Female; Humans; Hydrogen-Ion Concentration; Ion Channels; Male; Respiratory Mucosa; Respiratory System; Sodium-Potassium-Exchanging ATPase; Swine

Topics: Amphotericin B; Antifungal Agents; Cystic Fibrosis; Disease Progression; Exophiala; Humans; Interferon-gamma; Interleukin-17; Lung Diseases, Fungal; Male; Monitoring, Immunologic; Nitriles; Pyridines; Recombinant Proteins; Respiratory Function Tests; Sputum; Treatment Outcome; Triazoles; Young Adult

Cystic fibrosis (CF) is the most common monogenetic autosomal recessive disease in the human population. This systemic disease is characterized by changes in multiple organs, mainly in the lung tissue and digestive tract. More than 59% of CF patients become sensitized to fungal spores, mostly Aspergillus fumigatus. 5-15% of CF patients develop allergic bronchopulmonary aspergillosis. The aim of the study was to analyse the occurrence of yeast and filamentous fungi of the respiratory infections in CF patients and evaluation of drug resistance.. Between 2006 and 2014, mycological evaluation of 42 patients hospitalized at the National Institute of Tuberculosis and Lung Diseases was carried out.. 217 specimens from pulmonary tract were collected from 42 patients with cystic fibrosis. 205 (68%) strains of yeast and 96 (32%) filamentous fungi strains were cultured. The most common mould strain was A. fumigatus - 22,2% (67 species). All isolates of filamentous fungi were in vitro 100% susceptible to itraconazole, voriconazole, posaconazole and amphotericin B.. A. fumigatus and C. albicans were the most common etiological agents of fungal respiratory pathogens associated with CF patients. A. fumigatus strains were in vitro 100% susceptible to azole and amphotericin B. Two strains of C. albicans and one strain of C. tropicalis were non-susceptible to azole (fluconazole, itraconazole and voriconazole). Scedosporium apiospermum was resistant to amphotericin B (MIC > 32 mg/l) and susceptible to voriconazole (MIC 0.094 mg/l).

Topics: Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Candida albicans; Candida tropicalis; Cystic Fibrosis; Drug Resistance, Multiple, Fungal; Fungi; Humans; Itraconazole; Microbial Sensitivity Tests; Mycoses; Scedosporium; Triazoles; Voriconazole; Yeasts

Topics: Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Male

Topics: Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Male

We report the isolation of the emerging fungal pathogen Rasamsonia aegroticola, which belongs Rasamsonia argillacea species complex, from a respiratory sample of a patient with cystic fibrosis. This filamentous fungus, resembling members of a Penicillium and Paecilomyces spp., was identified by morphology and confirmed by DNA sequence analysis. Susceptibility pattern showed high minimal inhibitory concentration of voriconazole and amphotericin B but low minimal inhibitory concentration of caspofungin, micafungin and itraconazole.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Cystic Fibrosis; Echinocandins; Eurotiales; Humans; Lipopeptides; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Mycoses; Pharynx; Sequence Analysis, DNA; Slovenia; Voriconazole; Young Adult

This longitudinal prospective study aimed to determine the prevalence of oropharyngeal colonization by C. albicans in children with cystic fibrosis (CF), and observe the continuity of candidal colonization and the changes in production of virulence factors, susceptibility to antifungal agents and RAPD patterns of the isolates. Thirty-seven children with CF were followed-up for oropharyngeal C. albicans colonization for 18 months. The colonization rate was detected in 54%. All isolates were susceptible to amphotericin B, but those isolated from one patient were resistant to fluconazole. Biofilm production, secretory acid proteinase, phospholipase and esterase activity rates were 30%, 60%, 75% and 80%, respectively. RAPD analysis with the primers OPE-03 and OPE-18 was performed for genotyping. RAPD patterns of the strains isolated from the same patient were related to each other, whereas they were not related with other strains isolated from different patients. Two C. albicans strains isolated from the same patient were found to be unrelated to one another. As a result, long-lasting colonization of the oropharyngeal mucosa of children with CF by endogenous C. albicans isolates having the same RAPD pattern was demonstrated. Colonization prevalance and development of resistance to antifungal agents and the increased production of virulence factors were not correlated.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candida albicans; Child; Child, Preschool; Cystic Fibrosis; Drug Resistance, Fungal; Humans; Male; Oropharynx; Time Factors

The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated.. The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated.. In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition.. This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Body Mass Index; Child; Cystic Fibrosis; Diabetes Complications; Disease Progression; Female; Forced Expiratory Volume; Germany; Humans; Immunoglobulin G; Male; Steroids; Trichosporon; Trichosporonosis; Young Adult

Because published reports indicate that the antibiotic colistin (COL) has antifungal properties, this study investigated the antifungal in vitro activity of COL as single agent and in combination with the antifungal compounds voriconazole (VRC), caspofungin (CAS) and amphotericin B (AMB) against Scedosporium/Pseudallescheria spp., Exophiala dermatitidis and Geosmithia argillacea. In total, susceptibility was determined for 77 Scedosporium/Pseudallescheria spp., 82 E. dermatitidis and 17 G. argillacea isolates. The minimal inhibitory concentrations (MICs) of COL and the antifungals as single compound and in combination were determined with MIC test strips. Drug interactions were detected by crossing the MIC test strips at a 90º angle. The fractional inhibitory concentration index was used to categorise the drugs' interaction. The MIC50 value of COL was 12 μg ml(-1) for S. prolificans, 16 μg ml(-1) for P. apiosperma, 16 μg ml(-1) for P. boydii, 12 μg ml(-1) for E. dermatiditis and 6 μg ml(-1) for G. argillacea. VRC was the most active drug in combination without any antagonism with the exception of few P. boydii isolates. COL as single agent and in most combinations with antifungals exhibits in vitro antifungal activity against filamentous ascomycetes occurring in cystic fibrosis patients and may offer a novel therapeutic option, especially for multidrug-resistant S. prolificans.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Colistin; Cystic Fibrosis; Drug Evaluation, Preclinical; Drug Synergism; Echinocandins; Exophiala; Humans; Lipopeptides; Microbial Sensitivity Tests; Mitosporic Fungi; Mycoses; Pyrimidines; Scedosporium; Triazoles; Voriconazole

Invasive candidiasis is rare in children after the neonatal period, but can occur in children with (secondary) immunodeficiency with a damaged gastrointestinal or skin barrier, or when receiving antibiotics. A 10-month-old girl was diagnosed as suffering from cystic fibrosis (CF) when showing failure to thrive, pulmonary symptoms and hypoproteinaemia. At that time, Candida albicans was identified from blood culture and treated intravenously with liposomal amphotericin B for 13 days. Six weeks later, the girl presented with osteoarticular infection of the left knee caused by C. albicans. The infection showed insufficient response to therapy with liposomal amphotericin B, but the patient recovered after therapy with fluconazole and flucytosine. Follow-up over 4 years revealed no sequelae. In conclusion, invasive Candida infections may occur in patients with CF, and preventive measures might be considered in patients at risk. In the case of an invasive infection, prolonged treatment with a combination of antifungal drugs may be required.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidemia; Candidiasis, Invasive; Cystic Fibrosis; Female; Fluconazole; Flucytosine; Humans; Infant; Osteoarthritis; Treatment Outcome

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus fumigatus that occur frequently in patients with cystic fibrosis (CF). Recurrent episodes of bronchial obstruction, inflammation, and mucoid impaction occur in ABPA and results in bronchiectasis, fibrosis, and respiratory failure. The treatment of ABPA includes corticosteroids to reduce the acute inflammation and intraconazole to reduce the fungal colonization load in order to reduce lung injury. This case discusses the successful use of aerosolized amphotericin B for the treatment of ABPA in a 14-year-old patient with CF listed for lung transplant. The patient required fewer hospitalizations, and both oral corticosteroids and anti-fungal therapy were eventually stopped.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchiectasis; Cystic Fibrosis; Female; Humans; Immunoglobulin E; Immunoglobulin G; Itraconazole; Respiratory Function Tests; Severity of Illness Index; Sputum

This report describes the molecular epidemiology, in vitro susceptibility, colonial and microscopic morphologies, and biochemical features of Trichosporon mycotoxinivorans, a newly recognized pathogen that appears to have a propensity for patients with cystic fibrosis. The index patient died with histologically documented Trichosporon pneumonia complicating cystic fibrosis. This is also the first report of disease caused by a Trichosporon species in a nontransplant patient with cystic fibrosis. As T. mycotoxinivorans has not previously been recognized as a respiratory pathogen, the significance of its recovery from sputum samples was not initially appreciated. Genetic analysis of archived clinical samples found three additional cases of T. mycotoxinivorans infection which had previously been identified as other members of the genus. An additional isolate of T. mycotoxinivorans was identified from a clinical sample on initial testing. Three of these four cases were also patients with cystic fibrosis. All isolates had MICs at 48 h of amphotericin B of > or = 1 microg/ml and of echinocandins of > or = 16 microg/ml, but they displayed various susceptibilities to the triazoles. In summary, Trichosporon mycotoxinivorans is a newly recognized human pathogen that is associated with cystic fibrosis.

Topics: Amphotericin B; Antifungal Agents; Cystic Fibrosis; Echinocandins; Fatal Outcome; Humans; Lung; Lung Diseases, Fungal; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Mycoses; Radiography, Thoracic; Retrospective Studies; Triazoles; Trichosporon

Aspergillus fumigatus is a leading cause of death in immunocompromised patients and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and can contribute to antimicrobial resistance. We investigated the ability of A. fumigatus to form biofilms on polystyrene (PS) and human bronchial epithelial (HBE) and CF bronchial epithelial (CFBE) cells. We developed a novel in vitro coculture model of A. fumigatus biofilm formation on HBE and CFBE cells. Biofilm formation was documented by dry weight, scanning electron microscopy (SEM), and confocal scanning laser microscopy (CSLM). The in vitro antifungal activities of seven antifungal drugs were tested by comparing planktonic and sessile A. fumigatus strains. A. fumigatus formed an extracellular matrix on PS and HBE and CFBE cells as evidenced by increased dry weight, SEM, and CSLM. These biofilms exhibited decreased antifungal drug susceptibility and were adherent to the epithelial cells, with fungi remaining viable throughout 3 days. These observations might have implications for treatment of A. fumigatus colonization in chronic lung diseases and for its potential impact on airway inflammation, damage, and infection.

Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Biofilms; Bronchi; Cells, Cultured; Cystic Fibrosis; Drug Resistance, Fungal; Epithelial Cells; Humans; Microbial Sensitivity Tests; Microscopy, Confocal; Microscopy, Electron, Scanning; Respiratory Tract Infections

Topics: Administration, Inhalation; Adolescent; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child; Cystic Fibrosis; Drug Therapy, Combination; Humans; Nebulizers and Vaporizers; Respiratory Therapy

A case of endobronchitis by Scedosporium apiospermum in a child with cystic fibrosis is presented. The bronchial aspirate's cytology showed the presence of a large amount of septated-dichotomized hyphae. The bronchial aspirate's culture showed the presence of Scedosporium apiospermum in a pure culture of three consecutive samples. The scanning electron microscopy study of the mucosal surface revealed scarce mycelia with the presence of abundant conidiae. The transmission electron microscopy of the mucosa revealed inflammatory infiltrates constituted by macrophages, polymorphonuclear leukocytes, a lot of dichotomized mycelia and macrophages with hyphae and conidiae within the phagosomes. The patient was treated with amphotericin B and itraconazole.

Topics: Amphotericin B; Antifungal Agents; Bronchi; Bronchitis; Child; Cystic Fibrosis; Disease Susceptibility; Drug Therapy, Combination; Female; Humans; Itraconazole; Microscopy, Electron; Mycetoma; Respiratory Mucosa; Scedosporium

We report a rare case of mediastinal mass caused by Aspergillus fumigatus in a lung transplant recipient. The patient presented 9 months after bilateral lung transplantation for cystic fibrosis with intermittent fevers and new onset atrial fibrillation/flutter caused by a 7-cm mediastinal mass invading the left atrium. The mass was resected, and a prolonged course of voriconazole and caspofungin was given, which resulted in a complete clinical response. Despite long-term suppressive therapy with voriconazole, a relapse occurred 16 months after the initial diagnosis. This case highlights the challenges in the prevention and treatment of invasive aspergillosis in lung transplant recipients.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Caspofungin; Cystic Fibrosis; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Lipopeptides; Lung Transplantation; Magnetic Resonance Imaging; Mediastinal Diseases; Peptides, Cyclic; Postoperative Complications; Pyrimidines; Recurrence; Thoracoscopy; Triazoles; Voriconazole

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

A case of allergic bronchopulmonary Aspergillosis (ABPA) complicating lung transplantation for cystic fibrosis is described. Control of ABPA was only achieved with 20 mg of prednisone and 600 mg of itraconazole per day. However, a prompt clinical and physiologic response was observed when nebulized amphotericin was introduced, which allowed prednisone to be reduced to 7.5 mg per day and, in time, all anti-fungal therapy to be withdrawn.

Topics: Administration, Inhalation; Adult; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Drug Therapy, Combination; Glucocorticoids; Humans; Itraconazole; Lung Transplantation; Male; Prednisone; Tomography, X-Ray Computed

Although nephrotoxicity is a common and well-recognized side effect of amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with cystic fibrosis who developed fulminant renal and hepatic dysfunction following a short course of intravenous amphotericin B for a suspected aspergillus infection, although she did not have clinical evidence of invasive aspergillosis. The toxicity became apparent after changing to liposomal amphotericin. This association of renal and hepatotoxicity with liposomal amphotericin B has not previously been reported in children.

Topics: Amebicides; Amphotericin B; Aspergillosis; Child; Cystic Fibrosis; Female; Humans; Liver Failure; Renal Insufficiency

We report a case of invasive fungal pulmonary infection in a cystic fibrosis patient. Clinical deterioration coincided with isolation of Wangiella dermatitidis from her sputum, and treatment with amphotericin B followed by voriconazole resulted in clinical improvement and sterilization of the sputum. This case suggests that W. dermatitidis may be an etiologic agent of invasive pulmonary disease in the cystic fibrosis population.

Topics: Adult; Amphotericin B; Antifungal Agents; Cystic Fibrosis; Exophiala; Female; Hemoptysis; Humans; Lung Diseases, Fungal; Magnetic Resonance Imaging; Pyrimidines; Sputum; Triazoles; Voriconazole

The antimicrobial activities of amphotericin B, itraconazole, and miconazole against 101 filamentous fungi from patients with cystic fibrosis were tested by a reproducible microdilution method. Itraconazole was very active against Aspergillus species and Scedosporium species (MIC at which 90% of the isolates were inhibited [MIC90], 0.06 to 0.5 mg/liter), whereas amphotericin B was less effective (MIC90, 0.5 to 8 mg/liter).

Topics: Amphotericin B; Antifungal Agents; Aspergillus; Cystic Fibrosis; Itraconazole; Miconazole; Microbial Sensitivity Tests; Mitosporic Fungi

We describe a case of candidaemia in a paediatric cystic fibrosis (CF) patient with a totally implantable vascular access (TIVA). Serial quantitative blood cultures during therapy with amphotericin B delivered via the catheter suggested that the patient was responding to therapy. The TIVA was finally removed because of persistent fever, but its culture remained sterile. Randomly amplified polymorphic DNA (RAPD) analysis of Candida albicans from various anatomical sites showed that the patient's sputum was the most likely source of TIVA contamination. Investigation of TIVA-related candidaemia by molecular analysis could guide rational antifungal chemoprophylaxis of TIVA-related candidaemia.

Topics: Amphotericin B; Candidiasis; Catheters, Indwelling; Child; Cystic Fibrosis; DNA, Fungal; Female; Fungemia; Humans

Pulmonary aspergilloma is a rare complication of cystic fibrosis and is a contraindication to transplantation. The elimination of an aspergilloma in a 24 year old patient with cystic fibrosis by percutaneous instillation of amphotericin B is described, enabling her to be accepted on a lung transplantation programme.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Catheterization, Peripheral; Catheters, Indwelling; Cystic Fibrosis; Female; Humans; Itraconazole; Lung Diseases, Fungal; Radiography

The isolation of Aspergillus fumigatus from airway secretions from patients with cystic fibrosis (CF) is common and usually denotes asymptomatic colonization or allergic broncho-pulmonary aspergillosis (ABPA). A 12-year-old boy with CF acutely developed moderately severe symptoms of unremitting cough, fever, dyspnea, weight loss, and cyanosis. Chest radiographs demonstrated widespread unilateral infiltrates and volume loss. By bronchoscopy tenacious mucous plugs were seen occluding the left lower lobe bronchus. Cultures from sputum and sequential bronchoalveolar lavage grew Aspergillus fumigatus, but other significant criteria for diagnosing ABPA were lacking. No improvement was seen with a 3 week course of systemic corticosteroid and antibiotic therapy. Treatment with amphotericin B and short-term mechanical ventilation resulted in rapid resolution of all symptoms. This form of endobronchial aspergillosis has not been described previously.

Topics: Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Bronchoscopy; Child; Cystic Fibrosis; Humans; Male; Respiration, Artificial

Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ transport in CF, CF nasal epithelial cultures were studied with double-barreled Na(+)-selective microelectrodes and the Ussing chamber technique. Intracellular Na+ activity (acNa) was 24.1 +/- 1.5 mM (n = 36), a value similar to acNa of normal nasal epithelial cells. Reduction of luminal [Na+] to 3 mM abolished Ieq and reduced acNa. Amiloride (10(-4) M) abolished Ieq but increased acNa from 20 +/- 2 to 36 +/- 7 mM (n = 10). Amiloride-induced increase in acNa was not affected by serosal [Na+] reduction but was blocked by preexposure to reduced luminal [Na+]. Amphotericin B increased Ieq during amiloride exposure, indicating that amiloride did not inhibit NA(+)-K(+)-ATPase. Ouabain abolished Ieq and slowly raised acNa. Reduction of serosal [Na+] led to a decrease in acNa that was blocked by bumetanide. It is concluded that 1) CF airway epithelia exhibit an increased apical membrane Na+ permeability, 2) acNa is regulated to a normal level in CF cells despite increased transcellular Na+ fluxes, 3) the abnormal increase in acNa in response to amiloride is dependent on luminal Na+, 4) Na+ is transported across the basolateral membrane by a bumetanide-sensitive cotransport mechanism, and 5) ouabain inhibits the basolateral Na(+)-K(+)-ATPase, causing slow dissipation of the chemical and electrical gradients across the cell membranes.

Topics: Adolescent; Adult; Amiloride; Amphotericin B; Biological Transport; Bumetanide; Cells, Cultured; Child; Cystic Fibrosis; Electrophysiology; Epithelium; Female; Humans; Male; Nasal Mucosa; Osmolar Concentration; Ouabain; Sodium

Topics: Amphotericin B; Ampicillin; Autoradiography; Chloramphenicol; Culture Techniques; Cystic Fibrosis; Gentamicins; Humans; Intestinal Mucosa; Mucus; Neomycin; Organ Culture Techniques; Penicillins; Polymyxins; Rectum; Streptomycin; Sulfates; Sulfur Isotopes

Topics: Aerosols; Amphotericin B; Asthma; Bronchial Diseases; Bronchodilator Agents; Cystic Fibrosis; Eosinophilia; Isotonic Solutions; Lung Diseases; Mucus; Polymyxins; Radiography; Sodium Chloride; Spirometry; Sputum; Ultrasonics; Ventilators, Mechanical