Predisposing factors and outcome of uncommon yeast species-related fungaemia based on an exhaustive surveillance programme (2002–14)

International audienceObjectives:Using registry data to compare fungaemia caused by uncommon yeast species (UYS; i.e. other than Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis and Candida krusei ) and C. albicans -related fungaemia can reveal specific predisposing factors of UYS with potential impact on treatment strategies.Methods:We analysed 338 episodes of UYS fungaemia prospectively collected from 27 hospitals (Paris, France; 1 October 2002-31 December 2014) and compared these with 1998 single episodes of C. albicans fungaemia using univariate and multivariate analyses.Results:The proportion of UYS fungaemia was stable over time. Thirty-five different species were identified (27 ascomycetes, 8 basidiomycetes), 11 had caspofungin MIC 50  >0.25 mg/L and 15 fluconazole MIC 50  >4 mg/L. Haematological malignancies [OR=2.39 (95% CI 1.79-3.18)] and prior exposure to antifungal drugs [OR=1.87 (1.30-2.69)] were independent predisposing factors for UYS infections upon multivariate analysis. However, when considering the genus/species complex level, only infections due to Candida kefyr -related species [OR=4.01 (2.42-6.64)] and to Trichosporon spp. [OR=5.38 (1.72-16.81)] remained associated with haematological malignancies, those due to the GEOTRICHUM group with acute leukaemia [OR=61.29 (19.23-195.36)], and infections with Trichosporon spp. or the GEOTRICHUM group with prior exposure to caspofungin [OR=15.67 (3.62-67.80) and OR=13.17 (3.33-52.03), respectively] but not to fluconazole. The global mortality at day 30 for UYS was similar to that for C. albicans (35.4%, and 39.9%, respectively), but very divergent results were observed according to the specific UYS.Conclusions:UYS encompass a high diversity of species, each with its own behaviour and predisposing factors for human infections. This variety makes it important to rapidly identify an isolate to the species level in order to optimize antifungal treatment

Ten-Year Experience of Cutaneous and/or Subcutaneous Infections Due to Coelomycetes in France

International audienceBackground.  Coelomycetes are rarely but increasingly reported in association with human infections involving mostly skin and subcutaneous tissues, both in immunocompetent and immunocompromised patients. Coelomycetes constitute a heterogeneous group of filamentous fungi with distinct morphological characteristics in culture, namely an ability to produce asexual spores within fruit bodies. Methods.  We included all cases of proven primary cutaneous and/or subcutaneous infections due to coelomycetes received for identification at the French National Reference Center for Invasive Mycoses and Antifungals between 2005 and 2014. Eumycetoma, chromoblastomycosis, and disseminated infections were excluded. Results.  Eighteen cases were analyzed. The median age was 60.5 years. In all cases, patients originated from tropical or subtropical areas. An underlying immunodepression was present in 89% of cases. Cutaneous and/or subcutaneous lesions, mainly nodules, abscesses, or infiltrated plaques, were observed in distal body areas. Isolates of different genera of coelomycetes were identified: Medicopsis (6), Paraconiothyrium (3), Gloniopsis (3), Diaporthe (3), Peyronellaea (2), Lasiodiplodia (1). Lesion treatment consisted of complete (10) or partial (2) surgical excision and/or the use of systemic antifungal therapy, namely voriconazole (5) and posaconazole (4). Literature review yielded 48 additional cases of cutaneous and/or subcutaneous infections due to coelomycetes. Conclusions.  Infectious diseases physicians should suspect coelomycetes when observing cutaneous and/or subcutaneous infections in immunocompromised hosts from tropical areas; a sequence-based approach is crucial for strains identification but must be supported by consistent phenotypic features; surgical treatment should be favored for solitary, well limited lesions; new triazoles may be used in case of extensive lesions, especially in immunocompromised patients

Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival

International audienceSurgery and antifungals are the reference standard for rhino-orbito-cerebral mucormycosis (ROCM) treatment. The impact of local control on survival of 22 consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively, with or without local control (p <0.0001). Hence, repeated surgical procedures are recommended to achieve local control of ROCM

Thermothelomyces thermophila human infections

International audienc

Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010)

International audiencePURPOSE: To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and for death. METHODS: Active hospital-based surveillance program of incident episodes of candidemia due to common species in 24 tertiary care hospitals in the Paris area, France between October 2002 and September 2010. RESULTS: Among 2,507 adult cases included, 2,571 Candida isolates were collected and species were C. albicans (56 %), C. glabrata (18.6 %), C. parapsilosis (11.5 %), C. tropicalis (9.3 %), C. krusei (2.9 %), and C. kefyr (1.8 %). Candidemia occurred in ICU in 1,206 patients (48.1 %). When comparing ICU vs. non-ICU patients, the former had significantly more frequent surgery during the past 30 days, were more often preexposed to fluconazole and treated with echinocandin, and were less frequently infected with C. parapsilosis. Risk factors and age remained unchanged during the study period. A significant increased incidence in the overall population and ICU was found. The odds of being infected with a given species in ICU was influenced by risk factors and preexposure to fluconazole and caspofungin. Echinocandins initial therapy increased over time in ICU (4.6 % first year of study, to 48.5 % last year of study, p \textless 0.0001). ICU patients had a higher day-30 death rate than non-ICU patients (odds ratio [OR] 2.12; 95 % confidence interval [CI] 1.66-2.72; p \textless 0.0001). The day-30 and early (\textlessday 8) death rates increased over time in ICU (from 41.5 % the first to 56.9 % the last year of study (p = 0.001) and 28.7-38.8 % (p = 0.0292), respectively). Independent risk factors for day-30 death in ICU were age, arterial catheter, Candida species, preexposure to caspofungin, and lack of antifungal therapy at the time of blood cultures results (p \textless 0.05). CONCLUSIONS: The availability of new antifungals and the publication of numerous guidelines did not prevent an increase of candidemia and death in ICU patients in the Paris area

Changes in the epidemiological landscape of invasive mould infections and disease

Although a wide variety of pathogens are associated with invasive mould diseases, Aspergillus spp. have historically been one of the most common causative organisms. Most invasive mould infections are caused by members of the Aspergillus fumigatus species complex and an emerging issue is the occurrence of azole resistance in A. fumigatus, with resistance to amphotericin B documented in other Aspergillus spp. The epidemiology of invasive fungal disease has shifted in recent years as non-A. fumigatus Aspergillus spp. and other moulds have become progressively more important, although there are no consolidated data on the prevalence of less common species of moulds. The incidence of mucormycosis may have been underestimated, which is a potential concern since species belonging to the order Mucorales are more resistant to antifungal agents than Aspergillus spp. All species of Mucorales are unaffected by voriconazole and most show moderate resistance in vitro to echinocandins. Fusarium spp. may be the second most common nosocomial fungal pathogen after Aspergillus in some tertiary hospitals, and show a susceptibility profile marked by a higher level of resistance than that of Aspergillus spp. Recently, Scedosporium aurantiacum has been reported as an emerging opportunistic pathogen, against which voriconazole is the most active antifungal agent. Other mould species can infect humans, although invasive fungal disease occurs less frequently. Since uncommon mould species exhibit individual susceptibility profiles and require tailored clinical management, accurate classification at species level of the aetiological agent in any invasive fungal disease should be regarded as the standard of care.This Supplement was funded by Basilea Pharmaceutica International Ltd, Basel, Switzerland.S

Posttraumatic mucormycosis: a nationwide study in France and review of the literature

Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide "RetroZygo" study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high

Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry

International audienceMolecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae

Last Generation Triazoles for Imported Eumycetoma in Eleven Consecutive Adults

the French Mycosis Study GroupInternational audienceBackground: Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined.Methodology/Principal Findings: We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization.Conclusions/Significance: MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma