Geotrichosis: fungemia in a patient with acute lymphoblastic leukemia / Geotricosis: fungemia en paciente con leucemia linfoblástica aguda

Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, nonabscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.

La fungemia por Geotrichum spp. es poco frecuente y altamente letal. En el Instituto Nacional de Cancerología de Bogotá solo se han reportado dos casos: uno entre el 2001 y el 2007, y el otro entre el 2012 y el 2018. Este tipo de infección es más común en pacientes con algún grado de compromiso del sistema inmunitario, por lo que puede presentarse en pacientes con neoplasias hematológicas malignas. Se presenta el caso de un hombre de 27 años con recaída de leucemia linfoblástica aguda, que ingresó con poliartralgias de cinco días de duración. También cursaba con neutropenia febril, celulitis sin abscesos y bacteriemia por Staphylococcus aureus resistente a la meticilina para lo cual recibió terapia con oxacilina y cefepime. Sin embargo, persistía la neutropenia febril por lo que se sospechó una infección fúngica invasora. Se tomó un nuevo set de hemocultivos y se inició tratamiento antifúngico. En los hemocultivos se identificaron artroconidias y mediante espectrometría de masas por láser de matriz asistida de ionización-desorción se confirmó la presencia de Geotrichum spp. Se ajustó el tratamiento antifúngico con deoxicolato de anfotericina B por 14 días y voriconazol por cuatro semanas. Luego de una estancia prolongada se le dio de alta. Aunque la incidencia de la fungemia por Geotrichum spp. es baja, en pacientes con neoplasias hematológicas malignas debe considerarse en el contexto de una neutropenia febril que es persistente a pesar del tratamiento antimicrobiano de amplio espectro.

Geotricosis: fungemia en paciente con leucemia linfoblástica aguda / Geotrichosis: fungemia in a patient with acute lymphoblastic leukemia

La fungemia por Geotrichum spp. es poco frecuente y altamente letal. En el Instituto Nacional de Cancerología de Bogotá solo se han reportado dos casos: uno entre el 2001 y el 2007, y el otro entre el 2012 y el 2018. Este tipo de infección es más común en pacientes con algún grado de compromiso del sistema inmunitario, por lo que puede presentarse en pacientes con neoplasias hematológicas malignas. Se presenta el caso de un hombre de 27 años con recaída de leucemia linfoblástica aguda, que ingresó con poliartralgias de cinco días de duración. También cursaba con neutropenia febril, celulitis sin abscesos y bacteriemia por Staphylococcus aureus resistente a la meticilina para lo cual recibió terapia con oxacilina y cefepime. Sin embargo, persistía la neutropenia febril por lo que se sospechó una infección fúngica invasora. Se tomó un nuevo set de hemocultivos y se inició tratamiento antifúngico. En los hemocultivos se identificaron artroconidias y mediante espectrometría de masas por láser de matriz asistida de ionización-desorción se confirmó la presencia de Geotrichum spp. Se ajustó el tratamiento antifúngico con deoxicolato de anfotericina B por 14 días y voriconazol por cuatro semanas. Luego de una estancia prolongada se le dio de alta. Aunque la incidencia de la fungemia por Geotrichum spp. es baja, en pacientes con neoplasias hematológicas malignas debe considerarse en el contexto de una neutropenia febril que es persistente a pesar del tratamiento antimicrobiano de amplio espectro. La identificación de los agentes causantes de fungemias con herramientas de proteómica, como la espectrometría de masas mencionada, permite ajustar el tratamiento dirigido y reducir las complicaciones, la estancia hospitalaria y la mortalidad.

Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, non- abscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.

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.

Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study.

OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.

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.

A cluster of Geotrichum clavatum (Saprochaete clavata) infection in haematological patients: a first Italian report and review of literature.

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine-based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin-B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.

Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia

ABSTRACTEmpirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11-19) days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture). Because the patients' clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3-7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.

Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia.

Empirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11-19) days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture). Because the patients' clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3-7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.

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.