Rare Fungal Pathogens Research Articles

Identification and antifungal susceptibility profiles of Kodamaea ohmeri based on a seven-year multicenter surveillance study.

BackgroundKodamaea ohmeri has been a rare fungal pathogen in the past decades but is now becoming more common in various invasive fungal diseases, with high mortality. There are limited data on the occurrence and distribution of K. ohmeri.MethodsSixty-two K. ohmeri isolates collected from 24 hospitals in China over a 7-year period were studied. Performance of three phenotypic methods in the identification of this organism was assessed against a gold standard, 26S rDNA sequencing. Original identification results submitted by the participating local hospitals were reviewed. The Sensititre YeastOne YO10 (SYY) was evaluated in determining the in vitro antifungal susceptibilities using standard broth microdilution method (BMD) as a reference, and essential agreement (EA) was calculated.ResultsAccurate species identification was achieved in 82.3% and 96.8% of the cases by Vitek 2 Compact and Vitek mass spectrometry (MS), respectively. For Bruker MS, 12.9% and 96.8% of the isolates were correctly identified to species level using the direct transfer and protein extraction methods, respectively. Only 29 (46.8%) isolates were initially correctly identified as K. ohmeri by the local hospitals. The highest misidentification rate (100%, 16/16) was observed in CHROMagar. According to BMD, the highest MIC90 was seen in fluconazole (8 μg/mL), followed by 1 μg/mL for micafungin, caspofungin, 5-fluorocytosine, and amphotericin B, 0.5 μg/mL for itraconazole, 0.25 μg/mL for posaconazole and voriconazole. Significant differences in EAs for different drugs were observed, ranging from 95.2% for amphotericin B to 22.6% for itraconazole between SYY and BMD.ConclusionOur study emphasizes the need for accurate identification of clinical K. ohmeri isolates and the importance of validating antifungal susceptibility by standard BMD.

Detection and identification of fungi in bronchoalveolar lavage fluid from immunocompromised patients using panfungal PCR.

Rapid diagnostics of fungal pneumonia and initiation of appropriate therapy are still challenging. In this study, we used two panfungal assays to test bronchoalveolar lavage fluid (BALF) samples to prove their ability to confirm invasive fungal disease diagnosis and identify causative agents. Two methods targeting different fungal rDNA regions were used, and the obtained PCR products were sequenced directly or after cloning. In total, 106 BALF samples from 104 patients were tested. After sequencing, we obtained 578 sequences. Four hundred thirty-seven sequences were excluded from further analysis due to duplication (n = 335) or similarity with sequences detected in the extraction control sample (n = 102); 141 unique sequences were analyzed. Altogether, 23/141 (16%) of the fungi detected belonged to pathogenic species, and 63/141 (45%) were identified as various yeasts; a variety of environmental or very rare fungal human pathogens represented 29/141 (21%) of the total and 26/141 (18%) were described as uncultured fungus. Panfungal PCR detected fungal species that would be missed by specific methods in only one case (probable cryptococcosis). Panfungal PCR followed by sequencing has limited use for testing BALF samples due to frequent commensal or environmental fungal species pickup.

Fatal course of Saprochaete capitata fungemia in children with acute lymphoblastic leukemia

ABSTRACTSaprochaete capitata (S. capitata) is a very rare fungal pathogen that causes disseminated opportunistic infections in patients with hematologic malignancies. Fever resistant to broad-spectrum antibiotic and antifungal treatment is common in the presence of fungemia during the period of profound neutropenia. We describe three cases of leukemic children who died from S. capitata fungemia following a first febrile neutropenic episode after the induction of chemotherapy. S. capitata fungemia is an emergent infection associated with high mortality and low susceptibility to fluconazole and echinocandins. Awareness of this emergent infection is needed to ensure that it can be properly treated.

A Trichosporon asahii Bloodstream Infection in a Preterm Newborn with a Successful Outcome: A Case Report

Trichosporon asahii is a rare opportunistic fungal pathogen that causes fatal systemic infections in immunocompromised patients. We have reported a case of T. asahii fungemia in a low birth weight preterm newborn baby in the neonatal intensive care unit (NICU). This case of T. asahii fungemia was unresponsive to treatment with a combination of Amphotericin B and Fluconazole. However, Treatment with a combination of Voriconazole and Caspofungin was successfully eliminated the fungus from the blood of the infected patient.

Emerging Fungal Infections in Cancer Patients- A Brief Overview

The incidence of invasive fungal infections in immunocompromised cancer patients has continued to increase over the last few decades. With an increase in the use of broad spectrum antifungal prophylaxis, changes in transplant protocols, novel chemotherapeutic agents as conditioning regimens, use of potent B and T cell immunosuppressive agents to decrease the incidence of graft virus host disease, and an increase in the immunocompromised pool of patients, there has been a noticeable shift in the epidemiology of invasive fungal infections. Empiric therapy targeting frequently reported or expected fungal pathogens may fail because of the emergence of rare pathogens and a change in risk factors in the host. Emergence of rare yeasts and molds, often poses a challenge to clinicians involved in the care of these patients. This article provides a brief overview of rare fungal pathogens that have emerged in cancer patients over the last several years. It is meant to deliver an integrated and strategical approach for the diagnosis and management of these unique infections, from a clinical perspective.

Blastoschizomyces capitatus’un Neden Olduğu Üç Fungemi Olgusu

Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.capitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year-old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and amphotericin B after the identification of B.capitatus, and clinical improvement were noted during their follow-up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; BioMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45°C and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 µg/ml for amphotericin B; 2, 2, 16 µg/ml for fluconazole; 0.064, 0.032, 0.032 µg/ml for itraconazole and 0.125, 0.064, 0.064 µg/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 µg/ml for voriconazole and > 32 µg/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence-based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between two (case 1 and 2) strains and 94.9% similarity in one strain (case 3) of B.capitatus, however the transmission route could not be clarified due to the absence of environmental sampling. In conclusion, B.capitatus should also be considered as a cause of systemic fungal infections in immunocompromised patients. Determination of the in vitro antifungal susceptibilities of clinical B.capitatus strains may contribute to the therapeutic approaches and epidemiological data.

First reported case of subcutaneous hyalohyphomycosis caused by Paecilomyces variotii

Hyalohyphomycosis is a rare opportunistic fungal infection caused by saprophytes of genera such as Fusarium, Paecilomyces, Scedosporium, Penicillium, Scopulariopsis Acremonium, and similar fungi. The literature includes only one previous report of Paecilomyces variotii human infection and very few reports of subcutaneous mycosis caused by any of the hyalohyphomycosis group of fungi. We report an instance of fungal infection in a 50-year-old woman, known to have diabetes, who presented with multiple raised lesions on the upper back of twoyears' duration. Dermatological examination revealed a 20×22-cm, swollen, indurated area on the upper back with multiple violaceous, exophytic nodules on the surface. Microscopy from pus and tissue smear revealed septate branching fungi. Periodic acid Schiff (PAS) stain was positive for fungal elements. Culture on three occasions yielded P.variotii. Slide culture mounts showed septate hyaline hyphae of P.variotii with elongated phialides demonstrating bulbous bases and tapering apices attached to the conidiophores. The patient was treated with itraconazole, to which she responded well. This is the first reported case of subcutaneous hyalohyphomycosis caused by P.variotii. It appears that this relatively rare fungal pathogen may be starting to assert itself as an important cause of infection in humans.

Hospital-related outbreaks due to rare fungal pathogens: a review of the literature from 1990 to June 2011

Fungi can cause severe infections. Two or more nosocomial unusual fungal infections diagnosed in a short period should be assumed as an outbreak. The review's aim was to collect data to improve their management. The free online worldwide database for nosocomial outbreaks ( http://www.outbreak-database.com ) and the PubMed/MEDLINE database were used to collect the English literature published from 1990 to June 2011. The more common Candida spp. and Aspergillus spp. infections were excluded. For each outbreak, the following data were reviewed: species, duration, source and site of infection, ward, risk factors, number of patients infected, treatment, related mortality, type of epidemiological study and time elapsed between index cases and second cases. Thirty-six reports were considered: yeasts caused the majority of the outbreaks (16 out of 36). The median values for the overall duration, number of infected people per outbreak and infection-related mortality were 5months, 4 and 20%, respectively. Eighteen cases were caused by contaminated substances and 13 cases were hypothesised as human-transmitted. Nosocomial outbreaks due to rare fungal pathogens involve few patients but have high related mortality. These results could be explained by the diagnostic delay, the inability of recognising the source of the infections and the challenges of the treatment. More efforts should be concentrated to implement the application of proper hygiene practices to avoid human-human transmission.

Emergence of Aureobasidium pullulans as human fungal pathogen and molecular assay for future medical diagnosis

Despite the great importance of Aureobasidium pullulans in biotechnology, the fungus had emerged as an opportunistic human pathogen, especially among immunocompromised patients. Clinical detection of this rare human fungal pathogen presently relies on morphology diagnosis which may be misleading. Thus, a sensitive and accurate quantitative molecular assay for A. pullulans remains lacking. In this study, we presented the microscopy observations of A. pullulans that reveals the phenotypic plasticity of the fungus. A. pullulans-specific primers and molecular beacon probes were designed based on the fungal 18S ribosomal RNA (rRNA) gene. Comparison of two probes with varied quencher chemistry, namely BHQ-1 and Tamra, revealed high amplification efficiency of 104% and 108%, respectively. The optimized quantitative real-time PCR (qPCR) assays could detect and quantify up to 1pg concentration of A. pullulans DNA. Both assays displayed satisfactory performance parameters at fast thermal cycling mode. The molecular assay has great potential as a molecular diagnosis tool for early detection of fungal infection caused by A. pullulans, which merits future study in clinical diagnosis.

Candida ParapsilosisArthritis Involving the Ankle in a Diabetes Patient: A Case Report

Candida parapsilosis is a rare opportunistic fungal pathogen of the musculoskeletal region. Immune function of almost all patients is severely disturbed. Most reported cases of septic arthritis of joints by Candida involve the knee, especially Candida parapsilosis. To our knowledge, there has been only one case report of Candida parapsilosis involving the ankle presented on only plain radiography. We report a case of Candida parapsilosis arthritis involving the ankle in a diabetes patient which was shown on MR imaging.

Management of invasive fungal infections: a role for polyenes

The spectrum of invasive fungal infections (IFIs) continues to evolve with the emergence of rare and resistant fungal pathogens. Clinicians are faced with difficult diagnostic and treatment challenges in the management of immunocompromised patients at high risk of developing IFIs. Early and appropriate antifungal therapy is essential for a successful outcome when treating invasive mycoses. The armamentarium of antifungal drugs continues to grow; the three main classes of commonly administered drugs are the polyenes, azoles and echinocandins. The newer triazoles and the echinocandins have changed primary treatment options for some fungal infections, such as aspergillosis and candidiasis. However, despite their toxic potential, the oldest antifungal drugs, polyenes, remain useful in the treatment of IFIs because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients with breakthrough fungal infections. This review highlights important issues in the treatment of IFIs for consideration by clinicians.

Emerging & Rare Fungal Infections in Solid Organ Transplant Recipients

Emerging & Rare Fungal Infections in Solid Organ Transplant Recipients

Antifungal activity of NB-002, a topical nanoemulsion, against rare fungal pathogens of onychomycosis

Antifungal activity of NB-002, a topical nanoemulsion, against rare fungal pathogens of onychomycosis

Debaryomyces hansenii (Candida famata), a rare human fungal pathogen often misidentified as Pichia guilliermondii (Candida guilliermondii).

Debaryomyces hansenii is a hemiascomycetous yeast commonly found in natural substrates and in various types of cheese. Pichia guilliermondii is widely distributed in nature and is a common constituent of the normal human microflora. Both species have been described in human infections but are extremely difficult to differentiate phenotypically. Thus, frequent errors in identification occur. The 62 clinical and environmental isolates sent between 2000 and 2007 to the French National Reference Center for Mycoses and Antifungals as D. hansenii or P. guilliermondii were analyzed by using the carbon assimilation pattern, the presence of pseudohyphae, and sequencing of the ITS and D1/D2 regions of the rRNA gene. The objective of this study was to assess using nucleotide sequences whether phenotypic identification was accurate and whether phenotypic characteristics could be used to differentiate the two species when sequencing was not available. We found that 58% of the isolates were misidentified and belong to seven different species: P. guilliermondii, P. caribbica, P. jadinii, D. hansenii, Candida palmioleophila, C. haemulonii type II, and Clavispora lusitaniae. In conclusion, D. hansenii may not be as common a human pathogen as previously thought. Sequencing of either ITS or D1/D2 regions is a good tool for differentiating the species more frequently confused with D. hansenii, keeping in mind that reliable databases should be used.

Paecilomyces lilacinus fungemia in an adult bone marrow transplant recipient

Paecilomyces lilacinus is a rare fungal pathogen in humans. We report a case of fungemia caused by P.lilacinus in a non-neutropenic adult, 120 days after bone marrow transplant. The patient's primary risk factor was the presence of an indwelling vascular catheter. Her initial clinical course was characterized by fever, chills, and rigors. Blood cultures from the central line and peripheral veins were positive, as was a peripheral specimen drawn after removal of the catheter. Two initial peripheral specimens were positive for P.lilacinus only by blind subculture and/or sustained incubation. She developed peripheral pulmonary nodules following the fungemia, thus raising the possibility of disseminated disease, but definitive diagnosis was confounded by Pseudomonas bacteremia. The nodules cleared and she recovered following removal of the central line and treatment with amphotericin B and 5-fluorocytosine, despite in vitro resistance to these antifungal drugs. This case underscores the increasing importance of P. lilacinus as a human pathogen capable of producing disease in immunocompetent, as well as in immunocompromised hosts. Also of note is that blood culture systems may require extended incubation or subcultures in order to detect fungi.

Emergência de infecção por Trichosporon Asahii em pacientes portadores de insuficiência cardíaca em unidade de terapia intensiva cardiológica: relato de caso e revisão da literatura

Infection with the non-Candida yeast species Trichosporon have been recognized with increasing frequency over the last two decades. Invasive disease due to trichosporonosis has been reported from neutropenic patients with cancer and the mortality is high. Recently, others groups of patients have become susceptible to this rare fungi. We report the emerging of infection with pathogenic Trichosporon asahii in severely ill heart failure patients in a tertiary cardiological intensive care unit (CICU). We describe our data, and report a fatal case of disseminated trichosporonosis in a patient with heart failure. We also review literature pertaining to T. asahii infections. An 85 year-old woman with a history of hypertension, heart failure (ejection fraction (EJ): 30%) and pulmonary embolism was admitted to a medical cardiological ICU after cardiac arrest (ventricular fibrillation) resuscitated during a routine consultation. There were no neurological sequelae and the echocardiogram revels no changes, neither the cardiac biomarkers. Ventricular fibrillation was considered secondary to heart failure. The patient had extubation failure and difficult weaning needing long term mechanical ventilation even after tracheostomy. Her hospital course was complicated by acute renal failure and recurrent respiratory, urinary and systemic bacterial infections, which responded to broad-spectrum antibiotics. After a temporary improvement she developed urinary infection and subsequent septic shock. Cultures of urine and blood specimens grew T. asahii. Treatment with liposome amphotericin B (5 mg/kg/day) was started. Despite receiving vancomycin and imipenem, the clinical condition of the patient deteriorates. Blood taken for culture on the seventh day of amphotericin B therapy were negative but urine specimen still grew T. asahii. On the eighteenth day of antifungal therapy, the patient died with multiorgan failure. The increasing of severely ill patients, and the use of broad spectrum antibiotics, has predisposed the emerging of invasive infections by rare and new opportunistic fungal pathogens. Severe infection related to T. asahii, until recently restricted to neutropenic patients with cancer, has been frequently identified in heart failure patients with advanced age. The mortality is high. These data highlights the importance of considering this group of patients as a risk group for T. asahii infection.

Pichia farinosa Bloodstream Infection in a Lymphoma Patient

We describe a case of Pichia farinosa bloodstream infection in a lymphoma patient. Phenotypic methods failed to identify the isolate, which was identified by sequence-based methods. This case highlights the importance of implementing molecular methods for the identification of rare fungal pathogens.

P1467 Mixed infection of the lower limb caused by rare bacterial and fungal pathogens in a patient with multiple traumatic injuries

P1467 Mixed infection of the lower limb caused by rare bacterial and fungal pathogens in a patient with multiple traumatic injuries

Lung mass caused byPhoma exigua

We describe a well documented case of a fatal Phoma exigua lung infection in a patient with acute myeloid leukaemia and diabetes. The infection was histology and culture proven and a PCR assay was developed for detecting P. exigua DNA in deparaffinized lung-biopsy material. Confirmation of rare fungal pathogen infections requires a multidisciplinary approach involving clinical observations, mycology, histopathology and radiology.

Diagnose und Therapie von Pilzinfektionen und der Pneumozystis-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen

Invasive fungal infections are important causes of morbidity and mortality in pediatric cancer patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of fungal infections including Pneumocystis jiroveci. They are based on specific pediatric pharmacological and regulatory considerations and on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA). Recommendations for the most frequent clinical entities are summarized here. Options for initial therapy of uncomplicated candidemia include deoxycholate amphotericin B (DAMB), fluconazole (FLC), liposomal amphotericin B (LAMB), the combination of DAMB plus FLC as well as voriconazole (VCZ) for patients > 11 years. For acute disseminated candidiasis, the combination of DAMB plus flucytosine is recommended. Indwelling central venous catheters serve as infectious nidus and should be removed whenever feasible. First-line therapy for presumed or proven invasive Aspergillus infections in patients 12 years and older is VCZ with DAMB and LAMB serving as alternatives. Choices for patients < 12 years of age are essentially limited to DAMB and LAMB. Due to the yet lacking evidence for enhanced antifungal efficacy and the ongoing dosage finding of caspofungin (CAS) in pediatric patients, combination therapies (LAMB plus CAS or VCZ plus CAS) should only be considered for fulminant or massive, life threatening infections. In granulocytopenic patients, adjunctive therapy with colony-stimulating factors (G-CSF) is recommended. In patients under immunosuppressive therapy, glucocorticosteroids ought to be reduced or discontinued, if feasible. Surgical interventions are restricted to specific indications. Zygomyces infections are an indication for high-dose LAMB. The combination of DAMB plus flucytosine is the initial treatment of choice of cryptococcal mengoencephalitis, and for treatment of Pneumocystis jiroveci pneumonitis, trimethoprim/sulfamethoxazol or intravenous pentamidine is recommended. Beyond the listed entities, the article provides a brief review on the pharmacokinetics and dosing of antifungal agents in children and adolescents as well as detailed discussions and evidence-based recommendations for empirical antifungal therapy, diagnosis and treatment of superficial fungal infections, of invasive infections by previously rare fungal pathogens and endemic moulds and for adjunctive immunomodulatory and surgical interventions.