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Background: Invasive fungal diseases (IFD) remain a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) and are associated with high mortality rates in patients receiving alloHSCT. Antifungal prophylaxis is increasingly being used in the management of IFDs in patients receiving alloHSCT.Methods: A post-hoc analysis of the cross-sectional observational AFHEM study was carried out to describe the use of antifungal drugs in real-life clinical practice in alloHSCT recipients hospitalized in French hematological units.Results: A total of 147 alloHSCT recipients were enrolled; most were adults (n = 135; 92%) and had received alloHSCT < 6 months prior to enrollment (n = 123; 84%). Overall, 119 (81%) patients received a systemic antifungal therapy; of these, 95 (80%) patients received antifungal prophylaxis. Rates of patients receiving systemic antifungal treatment were similar irrespective of transplant time, neutropenic, and graft-versus-host disease status. Among patients on systemic antifungal treatment, 83 (70%) received an azole, 22 (18%) received an echinocandin, and 16 (13%) received a polyene.Conclusions: This work provides evidence of the antifungal strategies used in alloHSCT recipients hospitalized in French hematological units. Unlike earlier studies, the AFHEM study showed that prophylaxis appears to be the leading antifungal strategy used in alloHSCT recipients in France. [ABSTRACT FROM AUTHOR]

Because of chronic anemia, hypogonadotropic hypogonadism, and iron chelation, pregnancy in homozygous and heterozygous compound beta-thalassemia patients stays a challenge. Pregnancies of transfused beta-thalassemia women registered in the French National Registry, conducted between 1995 and 2015, are described. These pregnancies were compared with pregnancies in healthy women and to data previously published in the literature. Fifty-six pregnancies of 37 women were studied. There were 5 twin pregnancies. Assisted reproductive technologies (ART) were used in 9 pregnancies. Median term at delivery was 39 amenorrhea weeks, and median weight at birth was 2780 g. Cesarean section was performed in 53.6% of the pregnancies. There were 6 thromboembolic events, 6 serious infections, 6 pregnancy-induced hypertensions (PIH), 6 intrauterine growth retardations (IUGR), 5 severe hemorrhages, 4 gestational diabetes, 3 alloimmunizations, 2 heart diseases, and 1 pre-eclampsia. There were 5 infections and 4 osteoporosis in the first year of post-partum. ART and cesarean sections were more often used in the beta-thalassemia group, compared to control subjects. Thromboembolic events, PIH, hemorrhage at delivery, and IUGR were more frequent in the beta-thalassemia group. Time to delivery was not different, but infant weight at birth was significantly smaller in the beta-thalassemia group. In the post-partum period, global maternal complications were more frequent in the beta-thalassemia group. Pregnancy in transfused beta-thalassemia women is safe with rare obstetrical and fetal complications. Cesarean section remains often chosen, and infant weight at birth remains smaller than that in the general population, despite delivery at full term. [ABSTRACT FROM AUTHOR]

Rare fungal pathogens are emerging as agents of invasive fungal infections. We analyzed 13 cases of fungal infections caused by Kazachstania (Arxiozyma) spp. in Strasbourg University Hospital, Strasbourg, France. Among the cases, 4 patients had proven fungal disease (3 cases of invasive fungal disease and 1 mucocutaneous infection) and 9 were colonized by Kazachstania (Arxiozyma) spp. Candida albicans was also isolated from 11 of the 13 patients. None of the patients with proven invasive fungal disease met host criteria, but most had underlying diseases. All strains were identified as K. telluris by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and 3 were confirmed as K. bovina by internal transcribed spacer sequencing. For all tested strains, the MICs for fluconazole were >2 μg/mL. Emergence of this rare fungal infection might be explained by the increasing number of patients with immunocompromised conditions and gastroesophageal diseases. [ABSTRACT FROM AUTHOR]

Objectives The aim of our study was to assess the adherence to labelling and international guidelines for antifungal prescribing. Methods A retrospective study was performed in intensive care units in addition to the oncology and haematology department, which covered 70% of antifungal consumption at Hautepierre Hospital, Strasbourg, France. On reviewing medical charts, the antifungal prescription was examined in relation to the recommendations of indication, dosage, risk of drug–drug interactions and, where appropriate, antifungal susceptibility testing. Treatments were considered appropriate, inappropriate or debatable. Results Between January and April 2007, 199 treatments were given for 179 different episodes in 133 adult patients. Treatments were prescribed for pre-emptive or targeted therapy (n = 90, with 60 for candidiasis, 26 for aspergillosis and 4 for other mould diseases), empirical therapy (n = 17) and primary (n = 81) or secondary (n = 11) prophylaxis. Fluconazole accounted for 67% of prescriptions, followed by voriconazole (19%), caspofungin (10%), posaconazole (2%), conventional or liposomal amphotericin B (2%), itraconazole (<1%) and terbinafine (<1%). Indication and dosage were found to be appropriate in 65% and 62% of cases, inappropriate in 22% and 21%, and debatable in 13% and 17%, respectively. The overall (by combining all assessment criteria) rate of inappropriate use was 40%. The overall survival rate at 12 weeks was highest in patients receiving appropriate therapy (81% versus 72% and 68% in the debatable and inappropriate therapy groups, respectively), with between-group differences not being significant (P = 0.49). Conclusions Our evaluation revealed a high proportion of inappropriate or debatable use of antifungal agents, while highlighting significant issues, such as inadequate dosage or indications. [ABSTRACT FROM PUBLISHER]

This prospective, observational, multicenter study evaluated the real-world incidence of invasive fungal infection (IFI) during and after micafungin prophylaxis in France. Patients with a hematological malignancy/solid tumor received micafungin prophylaxis according to usual clinical practice and were followed for 3 months. Primary endpoint was breakthrough IFI incidence during prophylaxis. Secondary endpoints included the identification of IFI risk factors, IFI incidence during follow-up, and adverse events (AEs). One hundred and fifty patients (55 children, 95 adults) were enrolled. Micafungin prophylaxis was initiated at 50 mg in adults and at a median 1.01 mg/kg (range: 0.6–2.2) in children. Fifteen patients (10%) experienced an IFI during prophylaxis. IFI breakthrough occurred in 15% children, 7% adults, 3.1% allogeneic transplant patients, 8.7% acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients, 7.0% other patients (never allotransplanted/non-AML/MDS). Nineteen patients (12.7%) experienced an IFI during 3-month follow-up. Micafungin was well tolerated with few treatment-related AEs, supporting its use in this patient population in France. [ABSTRACT FROM AUTHOR]

Central nervous system involvement by malignant cells is a rare complication of Waldenström macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenström macroglobulinemia in 36% of patients. When Waldenström macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenström macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenström macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies., (Copyright© Ferrata Storti Foundation.)

Candida inconspicua and Candida norvegensis are two closely related species rarely involved in invasive infections. The purpose of this study was to depict the epidemiologic and clinical characteristics of candidemia due to these emerging fluconazole less susceptible species. A retrospective analysis of the epidemiology of C. inconspicua and C. norvegensis during the period 2006-2010 was initiated in six French University hospitals. From this, demographics, clinical, diagnostic and therapeutic data of C. inconspicua or C. norvegensis candidemia were recorded and compared to the observations reported in the literature. C. inconspicua was more frequently isolated compared to C. norvegensis (ratio 2.6) but from the same preferential body sites: mainly digestive (56.4% and 48.37%, respectively, for C. inconspicua and C. norvegensis) and respiratory (26% and 28.2%, respectively). Thirteen cases of candidemia were recorded and five additional cases were found in the literature. Hematogical malignancy was the main underlying disease (n = 12). Associated factors were the presence of a vascular catheter (n = 18), broad-spectrum antibiotics (n = 15), and neutropenia (n = 14). In 13 cases (72%), prior colonization was noted before the candidemia diagnosis. Combining the results for the two species, Minimal Inhibitory Concentrations (MIC50) of amphotericin B, fluconazole, voriconazole and caspofungin were 0.125, 48, 0.25, and 0.19 mg/l, respectively. These two species must be added to the growing list of emerging Candida species poorly susceptible to fluconazole.

Objectives: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD., Methods: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria., Results: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation., Conclusions: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.

Objectives: To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin., Methods: Retrospective, non-interventional study conducted in three University Hospitals., Results: Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis (n = 3), empirical therapy (n = 9) or directed therapy for candidemia (n = 5) or aspergillosis (n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis., Conclusions: Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the pharmacoepidemiology of the prescription of systemic antifungal agents in 48 French haematology, intensive care and infectious diseases units., Patients and Methods: Cases of invasive fungal infections (IFI) were identified retrospectively over a 1 year period. Data on underlying condition, IFI diagnosis, antifungal treatment and outcome were collected on the last five cases in each centre. Factors associated with first line therapy and with death were identified by multivariate analysis., Results: Two hundred and nine cases were included (102 aspergillosis, 86 candidiasis, 15 cryptococcosis). Amphotericin B, in different formulations, was the first line therapy in 60%, azoles in 32%, combinations in 8%. Haematological malignancies and neutropenia were associated with less frequent initial prescription of azoles [OR = 0.3 (0.1-0.8) and OR = 0.3 (0.1-0.9), respectively]. In aspergillosis, younger age and neutropenia were associated with less frequent initial prescription of azoles [OR = 0.03 (0.002-0.6) and OR = 0.09 (0.03-0.3), respectively] and previous history of IFI was associated with a higher probability of azole prescription [OR = 17.2 (2.4-124.3)]. In candidiasis, haematological malignancy and co-prescription of nephrotoxic agents were associated with a less frequent initial prescription of azoles [OR = 0.1 (0.04-0.4) and OR = 0.2 (0.06-0.9), respectively]. Three factors were associated with a lower risk of death: cryptococcosis [OR = 0.16 (0.03-0.98)], hospitalization in infectious diseases units [OR = 0.40 (0.16-0.97)] and recent surgery [OR = 0.26 (0.08-0.80)]. Severe renal insufficiency was associated with a higher probability of death [OR = 8.77 (1.97-38.97)]., Conclusions: Our results emphasize factors associated with the antifungal therapeutic decision and with the outcome of IFI.