Infección fúngica invasiva por Saprochaete capitata en un niño con aplasia medular / Invasive fungal infection by Saprochaete capitata in a child with bone marrow aplasia

RESUMEN Saprochaete capitata es una causa rara de infección fúngica invasiva en pacientes inmunocomprometidos con alta mortalidad y resistencia antifúngica. Presentamos el caso de un niño de cinco años con diagnóstico de aplasia medular, sometido a trasplante de progenitores hematopoyéticos (TPH), que cursó con neutropenia febril persistente, dolor abdominal intenso, aparición de lesiones maculopapulares en piel y deterioro de la función renal. Se identificó la presencia de S. capitata, en hemocultivos transcatéter venoso central. Esta infección fúngica invasiva resulta ser rara, pero emergente y potencialmente mortal, en pacientes con neutropenia febril persistente y uso prolongado de dispositivos invasivos intravasculares como catéter venoso central.

ABSTRACT Saprochaete capitata is a rare cause of invasive fungal infection in immunocompromised patients with high mortality and antifungal resistance. We present the case of a 5-year-old boy with bone marrow aplasia, who underwent hematopoietic stem cell transplantation (HSCT) and presented persistent febrile neutropenia, abdominal pain, appearance of maculopapular lesions on the skin, and impaired renal function. The presence of S. capitata was identified by blood culture from a central venous catheter. This invasive fungal infection is rare but emergent and life-threatening, especially in immunocompromised patients with persistent febrile neutropenia and prolonged use of invasive devices such as central venous catheters.

ß-1,3-d-Glucan and Galactomannan as Biomarkers for the Detection of Invasive Geotrichum and Magnusiomyces Infections: a Retrospective Evaluation.

Magnusiomyces and Geotrichum species are ascomycetous yeasts that can cause potentially life-threatening invasive fungal infections commonly referred to as geotrichosis. In this study, we aimed to estimate the incidence and mortality of these infections in a German tertiary care center. Furthermore, we evaluated the suitability of the fungal biomarkers galactomannan (GM) and ß-1,3-d-glucan (BDG), which are both recommended as surrogate markers for Magnusiomyces capitatus infection by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) joint clinical guidelines for the diagnosis and management of rare invasive yeast infections for detection of invasive geotrichosis. Cases meeting the inclusion criteria for invasive Magnusiomyces/Geotrichum infection were retrospectively identified. Serum samples and culture supernatants were analyzed with two commercially available fungal antigen tests (Platelia Aspergillus Ag EIA and Wako ß-glucan test). For a control cohort, outpatient samples sent for lues testing were included. Thirty-eight cases of Magnusiomyces/Geotrichum infection were identified over an 11-year observation period. In the majority of cases, the fungus was isolated from intra-abdominal specimens of patients with a history of abdominal surgery/procedures (n = 32). All cases of fungemia occurred exclusively in haemato-oncologic patients (n = 14). Thirty-day survival was 42% in the fungemia and 43% in the intra-abdominal geotrichosis group. Serum samples were available for 23 patients (14 bloodstream and nine intra-abdominal infections). While BDG sensitivity was 65%, none of the sera was GM positive. This finding was supported by in vitro experiments analyzing fungal culture supernatants: M. capitatus secretes significant amounts of BDG but not GM. Specificity was 96% for BDG and 100% for GM. Magnusiomyces and Geotrichum infections are not limited to haemato-oncologic patients. Contrasting the current ESCMID/ECMM recommendation, our results indicate that GM is no suitable biomarker for the diagnosis of Magnusiomyces infection. Contrarily, BDG sensitivity is comparable to that of candidemia.

Invasive Fungal Infection Caused by Geotrichum clavatum in a Child with Acute Leukemia: First Documented Case from Mainland China.

Invasive fungal infections are one of the vital complications among acute leukemia patients undergoing induction chemotherapy. Among them, Geotrichum clavatum infections present extremely rarely with atypical clinical symptoms which make them difficult to diagnose. In this paper, we report a case of infection caused by Geotrichum clavatum in a 10-year old child with acute leukemia, which is the first documented case from mainland China. With underlying childhood leukemia, the child suffered from recurrent bacterial and fungal infection and even underwent abdominal surgery during the treatment. Fortunately, the therapeutic effect was finally achieved by adjusting the treatment program to dual anti-fungal treatment with micafungin and amphotericin B. Information regarding the epidemiological, clinical, and therapeutic features, in this case, shows significant perspectives for anti-fungal treatment for immunocompromised individuals, wherefore the rate of recovery and survival can be achieved.

Date Palm Trees Root-Derived Endophytes as Fungal Cell Factories for Diverse Bioactive Metabolites.

Endophytic fungi of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) represent a promising source of bioactive compounds with biomedical, industrial, and pharmaceutical applications. The fungal endophytes Penicillium citrinum isolate TDPEF34, and Geotrichum candidum isolate TDPEF20 from healthy and BLD date palm trees, respectively, proved very effective in confrontation assays against three pathogenic bacteria, including two Gram-positive bacteria Bacillus thuringiensis (Bt) and Enterococcus faecalis (Ef), and one Gram-negative bacterium Salmonella enterica (St). They also inhibited the growth of three fungi Trichoderma sp. (Ti), Fusarium sporotrichioides (Fs), Trichoderma sp. (Ts). Additionally, their volatile organic compounds (VOCs) were shown to be in part responsible for the inhibition of Ti and Ts and could account for the full inhibition of Fs. Therefore, we have explored their potential as fungal cell factories for bioactive metabolites production. Four extracts of each endophyte were prepared using different solvent polarities, ethanol (EtOH), ethyl acetate (EtOAc), hexane (Hex), and methanol (MetOH). Both endophyte species showed varying degrees of inhibition of the bacterial and fungal pathogens according to the solvent used. These results suggest a good relationship between fungal bioactivities and their produced secondary metabolites. Targeting the discovery of potential anti-diabetic, anti-hemolysis, anti-inflammatory, anti-obesity, and cytotoxic activities, endophytic extracts showed promising results. The EtOAc extract of G. candidum displayed IC50 value comparable to the positive control diclofenac sodium in the anti-inflammatory assays. Antioxidant activity was evaluated using α,α-diphenyl-ß-picrylhydrazyl (DPPH), ß-carotene bleaching, reducing power (RP), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonique) (ABTS) radical scavenging assays. The findings revealed strong anti-oxidant power with an IC50 of 177.55 µg/mL for G. candidum EtOAc extract using DPPH assay, probably due to high polyphenol and flavonoid content in both fungal extracts. Finally, LC-HRMS (Liquid Chromatography­High Resolution Mass Spectrometry) and GC-MS (Gas Chromatography­Mass Spectrometry) analysis of G. candidum and P. citrinum extracts revealed an impressive arsenal of compounds with previously reported biological activities, partly explaining the obtained results. Finally, LC-HRMS analysis indicated the presence of new fungal metabolites that have never been reported, which represent good candidates to follow for the discovery of new bioactive molecules.

Geotrichum capitatum respiratory tract infection in a patient with polytrauma.

Geotrichum capitatum is a rare pathogen that causes opportunistic fungal infections in immunocompromised patients, particulary in patients with hematological malignancies. We report the case of a 72-year patient with polytrauma whose outcome was fatal. During his stay in the intensive care unit (ICU), he received a broad-spectrum antimicrobial therapy and underwent different invasive procedures. After becoming febrile on the 7th day of admission, two consecutive bronchoalveolar lavage (BAL) specimens were taken for microbiological analysis. The isolated species came as G. capitatum, that was identified using VITEK 2. Unfortunately, patient died before fungal identification, so the antifungal therapy wasn't administered. This case presentation emphasizes the importance of Geotrichum capitatum as an emerging fungal pathogen, as well as the significance of the predisponing factors that contributed to development of infection.

Geotrichum capitatum septicaemia in a haematological patient after acute myeloid leukaemia relapse: identification using MALDI-TOF mass spectrometry and review of the literature.

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

Geotrichum capitatum septicemia: case report and review of the literature.

Geotrichum capitatum is an uncommon cause of invasive infections in immunocompromised patients, particularly those with hematological malignancies and severe neutropenia. The aim of this study was to report the cases of invasive geotrichosis in our hospital. It is a retrospective study of invasive geotrichosis diagnosed in the Laboratory of Parasitology-Mycology of the UH Habib Bourguiba, Sfax, from January 2005 to August 2013. Six cases of invasive Geotrichum infections were diagnosed. There were three men and three women. The mean age was 35 years. Five patients have acute myeloid leukemia with a profound neutropenia, and one patient was hospitalized in the intensive care unit for polytraumatism. Clinically, the prolonged fever associated with pulmonary symptoms was the predominant symptom (n = 5). Geotrichum capitatum was isolated in one or more blood culture. Two patients had urinary tract infections documented by multiple urine cultures positive for G. capitatum. Five patients received conventional amphotericin B alone or associated with voriconazole. The outcome was fatal in four cases. Invasive geotrichosis is rare, but particularly fatal in immunocompromised patients. Approximately, 186 cases have been reported in the literature. The prognostic is poor with mortality over 50 %. So, early diagnosis and appropriate management are necessary to improve prognosis.

Invasive Geotrichum clavatum fungal infection in an acute myeloid leukaemia patient: a case report and review.

Invasive Geotrichum clavatum fungal infections are extremely rare and unusual, occurring nearly exclusively in patients experiencing prolonged neutropenia during the treatment for acute myeloid leukaemia. Several groups of cases of fatal G. clavatum infection were reported in France between 2011 and 2012, but the ecological niche has not yet been identified. We report a case of a 32-year-old patient with acute myeloid leukaemia who developed G. clavatum sepsis with primary peritonitis, hepatic nodular lesions, and multivisceral failure during aplasia after induction followed by salvage chemotherapy. He was treated with voriconazole and is still alive 1 year after with controlled disease. We then discuss the epidemiological, clinical, and therapeutic features of these serious fungal infections compared to the published data.

[Double fungemia. Report of four Tunisian cases]. / Les fongémies mixtes. À propos de quatre cas tunisiens.

UNLABELLED: Fungemia is classically caused by a single species and the detection of more than one species in blood samples is uncommon. We report four cases of mixed fungemia (MF) diagnosed in the parasitology-mycology laboratory of Farhat-Hached hospital in Sousse, Tunisia. The MF episodes occurred in two neonates and two adults suffering from acute myeloid leukemia. Two fungal species were detected concomitantly within the same blood culture in all cases. Species combination was detected by the subculture of the blood culture on Candida ID(®) chromogenic medium in three cases and on Sabouraud agar in one case. Predisposing factors were: indwelling catheters (4/4), broad-spectrum antibiotics (3/4), neutropenia (2/4), exclusive parenteral nutrition (2/4) and Candida colonization (1/4). Patients presented febrile sepsis with no response to broad-spectrum antibiotic therapy in all cases. Outcome under antifungal treatment was favorable in two cases and the two other patients died. CONCLUSION: MF appears similar to the more common monomicrobial fungemia. The use of chromogenic media in routine can improve the detection of MF episodes allowing appropriate antifungal therapy.

Geotrichum capitatum septicemia in a hematological malignancy patient with positive galactomannan antigen: case report and review of the literature.

Geotrichum capitatum, formerly known as Trichosporon capitatum, is an uncommon but frequently fatal invasive fungal infection in immunocompromised patients, especially in hematological malignancies. We report a seven-year-old patient with acute myeloid leukemia with Geotrichum septicemia with involvement of the lungs, liver, spleen, and kidneys, who had a favorable outcome after therapy. Alteration of antifungal treatment to liposomal amphotericin B resolved the fever with favorable clinical response.

Breakthrough Saprochaete capitata infections in patients receiving echinocandins: case report and review of the literature.

We report a rare case of a fatal Saprochaete capitata breakthrough infection in a patient with acute myeloid leukemia receiving empirical caspofungin therapy. S. capitata is an uncommon, yet emerging cause of invasive infections, especially in patients with haematological malignancies. Blood cultures from our patient yielded S. capitata which was found to be resistant, in vitro, to caspofungin. We consecutively reviewed all published cases of breakthrough infections caused by S. capitata in patients receiving echinocandins. S. capitata should be considered in those patients who remain febrile or who develop invasive mould infections while under echinocandin therapy.

[Fungi as emergent etiologic agents in ventilator-associated pneumonia after cardiac surgery]. / Fungii ca agenti etiologici emergenti ai pneumoniei asociata ventilatiei mecanice post-chirurgie cardiaca.

UNLABELLED: Evaluation of the fungal involvement in the etiology of ventilator-associated pneumonia (VAP) after cardiac surgery. The study had as target the patients diagnosed with VAP after cardiac surgery at the Institute of Cardiovascular Diseases in Iasi, between April 2nd 2002 and December 31st 2009. MATERIAL AND METHOD: Our study included only cases with fungal etiology of VAP. We examined quantitatively the tracheal aspirates with cytology quality score Q = 2+: microscopy and cultivation. The isolates with clinical significance (= 10(6)UFC/mL significantly associated to inflammatory cells) were identified by standard methods or based on the API system (bioMérieux) and tested by the breakpoints method for susceptibility to antifungal agents. RESULTS: Among the 2167 operated patients, 35 of them were diagnosed with VAP through the clinical pulmonary infection score = 6. Fungi caused 15 of 44 VAP episodes. With a frequency of 30.19%, fungi are on 2nd place within the etiologic agents of VAP after non-fermenting Gram-negative bacilli (45.28%). The fungi involved in VAP were: Candida albicans (16.97%), Pneumocystis jirovecii (3.77%), while Candida glabrata, Candida sake, Candida krusei, Geotrichum capitatum and Cryptococcus humicola, amounted 1.89% each. The widespread use of broad spectrum antibiotics led to the emergence of fungi as a common cause of ventilator-associated pneumonia. The involvement in the VAP etiology of P. jirovecii, an un-cultivable fungus with special sensitivity to antibiotics, requires a careful microscopy of specimens.

Screening of microbial lipases and evalutaion of their potential to produce glycerides with high gamma linolenic acid concentration

Gamma-linolenic acid (GLA, 18:3, cis- 6,9,12-octadecatrienoic acid), an important compound in n-6 eicosanoid family biosynthesis, occurs in the lipids of a few plant and microbial sources. This study focused on the screening of microbial strains with suitable lipase activity for enrichment of GLA by selective hydrolysis of the borage oil (21.6 percent of GLA/total fatty acids). Firstly, 352 microrganisms were tested for their lipolytic capacity using screening techniques on agar plates containing borage oil, strains were then selected and screened for their activity (U/mg) using both submerged fermentation (SmF) and solid state fermentation (SSF). The rate of hydrolysis and the selective preference of these hydrolytic enzymes towards fatty acids, with a special focus on enrichment of GLA were studied and compared with those obtained by two commercially-available lipases. Only one of the lipases tested during this study displayed selectivity, discriminating the GLA during the hydrolysis reaction. Using the enzymatic extract from Geotrichum candidum as a biocatalyst of the reaction, it was possible to obtain a percentage of 41.7 percent of GLA in acylglycerols fraction when the borage oil was treated in a fixed-bed reactor for 24 hours at 30ºC.