First endogenous fungal endophthalmitis due to Fusarium dimerum: A severe eye infection contracted during induction chemotherapy for acute leukemia.

Endophthalmitis is a rare infection of the vitreous and/or aqueous. It can be bacterial or fungal. Exogenous endophthalmitis is the most common form and results from direct inoculation of a pathogen after eye surgery or penetrating trauma. Endophthalmitis can also be endogenous, secondary to disseminated infection. Fungal endophthalmitis is associated with poor prognosis and treatment is difficult given the low penetration of most of the antifungal agents available and the emergence of resistant filamentous fungi like Fusarium. To our knowledge, we describe the first endogenous fungal endophthalmitis due to Fusarium dimerum, a ubiquitous pathogen found in soil and plants. A 71-year-old woman, diagnosed with acute myeloid leukemia, was hospitalized for surveillance after induction chemotherapy. Prophylaxis by antibiotics and posaconazole was ongoing when she complained of pain and decreased vision in the left eye. A voluminous chorioretinal abscess developed and after multiple sterile aqueous humour samples, only vitrectomy allowed diagnosis with fungal hyphae seen on May-Grünwald Giemsa stained smear and positive cultures. The fungus was identified as Fusarium dimerum. The treatment, that included intravitreal injections of voriconazole and amphotericin B associated with systemic administration of voriconazole, allowed complete control of the infection. The source of this infection could not be confirmed despite the discovery of several possible infection sites including a periungual whitlow on the left hand and a lesion on a nail, from which samples were negative in microbiology laboratories. Unfortunately, damages of the retina were too important and the patient did not recover sight of her left eye.

Validation of a New Web Application for Identification of Fungi by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has emerged as a reliable technique to identify molds involved in human diseases, including dermatophytes, provided that exhaustive reference databases are available. This study assessed an online identification application based on original algorithms and an extensive in-house reference database comprising 11,851 spectra (938 fungal species and 246 fungal genera). Validation criteria were established using an initial panel of 422 molds, including dermatophytes, previously identified via DNA sequencing (126 species). The application was further assessed using a separate panel of 501 cultured clinical isolates (88 mold taxa including dermatophytes) derived from five hospital laboratories. A total of 438 (87.35%) isolates were correctly identified at the species level, while 26 (5.22%) were assigned to the correct genus but the wrong species and 37 (7.43%) were not identified, since the defined threshold of 20 was not reached. The use of the Bruker Daltonics database included in the MALDI Biotyper software resulted in a much higher rate of unidentified isolates (39.76 and 74.30% using the score thresholds 1.7 and 2.0, respectively). Moreover, the identification delay of the online application remained compatible with real-time online queries (0.15 s per spectrum), and the application was faster than identifications using the MALDI Biotyper software. This is the first study to assess an online identification system based on MALDI-TOF spectrum analysis. We have successfully applied this approach to identify molds, including dermatophytes, for which diversity is insufficiently represented in commercial databases. This free-access application is available to medical mycologists to improve fungal identification.

[Disseminated fungal infection due to Magnusiomyces capitatus in a liver graft patient]. / Infection fongique disséminée à Magnusiomyces capitatus chez un patient transplanté hépatique.

Disseminated fungal infections due to Magnusiomyces capitatus are rare, occurring exclusively in immunocompromised patients. We report the first case in a liver transplant patient with chronic rejection and portal thrombosis who had a M. capitatus fungemia with a refractory septic shock. Despite an antibacterial and antifungal treatment with caspofungin empirical treatment, the patient died from multiple organ failure. Subsequently, mycological examinations of blood cultures, bronchoalveolar lavage fluid and urine were positive to M. capitatus identified by mass spectrometry and confirmed by sequencing respectively. The stain was resistant to caspofungin and fluconazole. The best treatment appears to be the combination of amphotericin B and voriconazole or amphotericin B and 5 fluorocytosine.

Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients.

Pneumocystis jirovecii pneumonia (PCP) is an acute and life-threatening lung disease caused by the fungus Pneumocystis jirovecii The presentation of PCP in HIV-positive patients is well-known and consists of a triad of dyspnea, fever, and cough, whereas the presentation of PCP in HIV-negative patients is atypical and consists of a sudden outbreak, O2 desaturation, and a rapid lethal outcome without therapy. Despite the availability of direct and indirect identification methods, the diagnosis of PCP remains difficult. The cycle threshold (CT) values obtained by quantitative PCR (qPCR) allow estimation of the fungal burden. The more elevated that the fungal burden is, the higher the probability that the diagnosis is pneumonia. The purposes of the present study were to evaluate the CT values to differentiate colonization and pneumonia in a population of immunocompromised patients overall and patients stratified on the basis of their HIV infection status. Testing of bronchoalveolar lavage (BAL) fluid samples from the whole population of qPCR-positive patients showed a mean CT value for patients with PCP of 28 (95% confidence interval [CI], 26 to 30) and a mean CT value for colonized patients of 35 (95% CI, 34 to 36) (P < 10(-3)). For the subgroup of HIV-positive patients, we demonstrated that a CT value below 27 excluded colonization and a CT value above 30 excluded PCP with a specificity of 100% and a sensitivity of 80%, respectively. In the subgroup of HIV-negative patients, we demonstrated that a CT value below 31 excluded colonization and a CT value above 35 excluded PCP with a specificity of 80% and a sensitivity of 80%, respectively. Thus, qPCR of BAL fluid samples is an important tool for the differentiation of colonization and pneumonia in P. jirovecii-infected immunocompromised patients and patients stratified on the basis of HIV infection status with different CT values.

Prostatic and renal aspergillosis due to Aspergillus fumigatus in a patient receiving alemtuzumab for chronic lymphocytic leukaemia.

OBJECTIVE: Treatment of chronic lymphocytic leukaemia (CLL) is rapidly evolving, with emerging new drugs. Alemtuzumab is a monoclonal antibody recognizing CD52 antigen approved in the treatment of relapsing-refractory CLL. A frequent side effect is the immunosuppression and patients treated with alemtuzumab risk to develop fungal infections such as aspergillosis. PATIENT AND METHODS: This case report is about a patient who developed an uncommon localization of aspergillosis: prostatic and renal, after a treatment by alemtuzumab monotherapy. During the week 8 of alemtuzumab, the patient presented fever, urinary frequency and urologic symptoms. Persistance of fever with common antibiotherapy led to realize a tomography that showed prostatic and renal abscess (70mm and 29mm). It was decided to realize a prostatic biopsy. RESULTS: Histological findings showed suppurative abscess with ischemic necrosis and fungal proliferation, with branched fungal hyphae. Direct examination was negative. Culture on Sabouraud's agar revealed a mould identified as Aspergillus fumigatus. The organism was susceptible to voriconazole (MIC: voriconazole 0,25ug/mL). CONCLUSION: Because of the main side effect of alemtuzumab is immunosuppression, we have to research fungal infections such as Aspergillosis, particularly in patients with fever resistant to common antibiotherapy.

A 6-year antifungal stewardship programme in a teaching hospital.

PURPOSE: To describe the antifungal stewardship programme in our hospital and to assess its impact on total antifungal prescriptions and their cost, and on the process of care measures regarding the diagnostic and therapeutic management of invasive aspergillosis and candidaemia. METHODS: We conducted a prospective observational study describing the multifaceted antifungal stewardship programme in place at our French teaching tertiary-care hospital since 2005. Several actions were implemented successively, including the systematic evaluation of all costly antifungal prescriptions (echinocandins, lipid formulations of amphotericin B, posaconazole and voriconazole). RESULTS: A total of 636 antifungal prescriptions were discussed by the antifungal management team from 2005 to 2010 inclusive, mainly from the haematology department (72 %). In 344/636 cases (54 %), a piece of advice was fed back to the physician in charge of the patient, with an 88 % compliance rate. Optimal standard of care was achieved for galactomannan antigen testing, performance of chest computed tomography (CT) scan and voriconazole therapeutic drug monitoring for invasive aspergillosis, with no combination therapies used since 2008. Regarding candidaemia, optimal standard of care was achieved for the timing of antifungal therapy, recommended first-line therapy, duration of therapy and the removal of central venous catheters. Total antifungal prescriptions (in defined daily doses, DDD) and their cost were contained between 2003 and 2010. CONCLUSIONS: The implementation of an antifungal stewardship programme was feasible, sustainable and well accepted. We observed an improved quality of care for some process of care measures, and antifungal use and cost were contained in our hospital.

Interlaboratory reproducibility of Etest amphotericin B and caspofungin yeast susceptibility testing and comparison with the CLSI method.

This study aimed to assess the interlaboratory reproducibility at four university hospital laboratories in the southeast region of France of the Etest technique for the determination of caspofungin (CAS) and amphotericin B (AMB) MICs and to compare it to the CLSI broth microdilution reference method. Consecutive clinical yeast isolates (n = 198) were included in the study. AMB and CAS MICs were read at 24 and 48 h. Interlaboratory reproducibility was estimated by using (i) an intraclass correlation coefficient (ICC), (ii) essential agreement (EA), and (iii) categorical agreement (CA). For Etest interlaboratory reproducibility for CAS, ICCs were 0.80 (95% confidence interval [CI], 0.76 to 0.84) and 0.81 (95% CI, 0.77 to 0.85) at 24 and 48 h, respectively. For AMB, the ICCs were 0.51 (95% CI, 0.43 to 0.58) and 0.69 (95% CI, 0.63 to 0.74) at 24 and 48 h, respectively. At 48 h, the between-center EAs ranged from 94.4 to 99.0% for both antifungals. For the comparison of the CLSI method and the Etest, the between-technique ICCs were 0.69 (95% CI, 0.63 to 0.74) and 0.62 (95% CI, 0.55 to 0.68) for CAS and AMB, respectively. The EAs ranged from 76.5 to 98.5% for CAS and from 90.3 to 97.4% for AMB according to the centers. CAs ranged from 87.9% to 91.4%, with four very major errors for 2 strains (1 Candida albicans strain and 1 Candida krusei strain), for CAS and from 97.5 to 99.5%, with four major errors, for AMB. In conclusion, the Etest showed a good interlaboratory reproducibility and a good correlation with the CLSI technique. It is well suited for the routine clinical laboratory and can thus be used to monitor clinical yeast isolates' in vitro susceptibilities in this setting.

Outcome of exfoliative rejection after isolated intestinal transplantation in an adult: case report.

A 34-year-old-man with short-bowel syndrome received an isolated small bowel graft. On postoperative day (POD) 11, ileal biopsy specimen demonstrated mild to moderate rejection that did not respond to corticosteroid bolus therapy. On POD 14, endoscopy and histologic examination revealed exfoliative rejection that was not controlled after 14 days of therapy with thymoglobulin. On POD 95, the patient underwent surgery again because of intestinal obstruction. The graft was removed 6 months after transplantation because of continuous severe abdominal pain with weight loss. After enterectomy, the patient developed multiple-organ failure and died on POD day 8. This case underlines the severity of exfoliative rejection and suggests that early enterectomy be performed when the diagnosis is made, before deterioration of clinical status and development of infectious and nutritional complications.

A century of leishmaniasis in Alpes-Maritimes, France.

A century of publications on leishmaniasis in Alpes-Maritimes, in southern France, is here reviewed. Autochtonous human and canine leishmaniasis were first recognised in this département, which lies by the Mediterranean Sea and near the Italian border, in 1918 and 1925, respectively. The parasite responsible for the leishmaniasis, Leishmania infantum, is transmitted by Phlebotomus perniciosus and P. ariasi. The human leishmaniasis is zoonotic, with domestic dogs acting as the main 'reservoir' hosts. In prospective surveys over the last two decades, a mean of 12% of the domestic dogs checked in Alpes-Maritimes have been found seropositive for L. infantum but only about 50% of the seropositive animals showed any clinical signs of infection at the time of the surveys. During the last 30 years, 178 cases of human visceral leishmaniasis have been recorded in the area. Such cases are sporadic and often opportunistic, occurring predominantly in children (29% of the 178 cases) or HIV-positive subjects (31%). Recently, it has been demonstrated that, in Alpes-Maritimes, approximately 20% of those found seropositive in leishmanin skin tests are asymptomatic carriers, with amastigotes in their peripheral blood.

A pseudo tumoral sinusitis caused by Bipolaris sp.

This is the first published French case of a rhinosinusitis caused by Bipolaris sp. in an immunocompetent patient and suggests that this organism must be considered as an opportunistic human pathogen in warm and damp climate like the south-east of France. Bipolaris sp. is the most isolated fungi in allergic fungal sinusitis.

Human trichinellosis due to Trichinella britovi in southern France after consumption of frozen wild boar meat.

Six patients were infected with Trichinella britovi in southern France following consumption of frozen wild boar meat, which had been frozen at -35 degrees C for 7 days. Microscopic examination of a sample of frozen wild boar muscle revealed the presence of rare encapsulated Trichinella larvae, identified as T. britovi. People eating wild boar must follow individual prophylactic rules such as efficient cooking of meat (at least 65 degrees C at the core for 1 minute) as recommended by the International Commission on Trichinellosis, or freezing exceeding four weeks at -20 degrees C.

[Kidney transplant and Candida albicans arteritis. The importance of analysing the transplant conservation liquid]. / Greffe rénale et artérite du greffon à Candida albicans. Importance de l'analyse du liquide de conservation du greffon.

INTRODUCTION: Candida arteritis can compromise the functional prognosis of the graft or even the life of the transplant recipient. The infection can be transmitted by the graft. OBSERVATION: A 46 year-old woman contracted a Candida albicans ateritis of the graft following a kidney transplant that led to a detransplantation. The yeast was probably transmitted by the graft from the donor, source of an unknown candida infection: it was found in the conservation liquid of the graft itself, and in the renal artery and vascular pedicle. Analysis of of these three elements by enzymatic electrophoresis showed that they were identical. COMMENTARIES: This case report underlines the need to establish guidelines and sanitary safety measures, notably that of systematically placing in culture the concervation solutions and alerting the transplant team if any fungi are isolated.

[Delayed diagnosis of neurocysticercosis: two case reports]. / Neurocysticercose de diagnostic tardif: à propos de deux cas.

INTRODUCTION: Neurocysticercosis is the most frequently encountered cerebral parasitic infection worldwide. It is due to infection of the central nervous system by Taenia solium larval form. According to the location of the cysts, parenchymal and extra-parenchymal forms may be identified, with different clinical expressions. EXEGESIS: We report two cases of neurocysticercosis, one with typical parenchymal involvement and the second with extra-parenchymal involvement revealed by increased intra-cranial pressure. In both cases, the diagnosis was established over 10 years after the onset of symptoms. CONCLUSION: Neurocysticercosis is very frequent in non-Islamic developing countries, and its incidence is increasing in industrialized nations in relation to tourism and immigration from highly endemic areas. Symptoms usually appear several years after infection and this accounts for the frequent delays before the diagnosis is established.

[Diagnosis of aspergillosis and other invasive filamentous fungal infections in hematology]. / Diagnostic de l'aspergillose et des autres infections invasives à champignons filamenteux en hématologie.

OBJECTIVE: Invasive filamentous fungal infections (FFI) are difficult to diagnose in the department of hematology; a variety of arguments are necessary to confirm the fungal origin. Our study evaluated prospectively, in a large population in South Eastern France, the diagnostic techniques used ante and post mortem (mycology, anatomopathology, serology and aspergillosis antigens) to prove an FFI. METHODS: Two hundred and twenty eight neutropenic patients with obvious, probable, highly probable or presumed FFI were selected. Since completion of this study, a new classification of aspergillosis, with 3 instead of 4 levels of diagnosis, has been defined by the ICAAC in San Francisco but has not yet been published. Mycological or histological examinations were been performed on broncho-alveolar washings (BAW), puncture liquids or biopsies. Serology used precipitation, hemagglutination, immunofluorescence or ELISA techniques. Aspergillosis antigens were researched using the Pastorex method (agglutination of latex particles), launched at the beginning of the study. RESULTS: Invasive aspergillosis was diagnosed in 43.4% of patients, a non-aspergilla FFI in 6.5%, and no fungi was isolated in the cultures of 50% of patients. Ante mortem, 160 patients underwent BAW with a total of 175 samples. Among the latter, 41.7% mycological examinations were positive (presence of mycelium filaments and/or positive cultures) with 68.7% of Aspergillus fumigatus. Of the 48 puncture liquids, 25% of direct examinations and 29% of cultures were positive. Biopsies were taken from 59 patients and explored for mycology: 63.8% of direct examinations and 46.8% of cultures were positive; for those explored histologically, 76.7% revealed the presence of mycelium filaments. Post mortem, 17 patients out of 79 deceased underwent a total of 24 autopsy or biologic sampling. For 5 patients, FFI was diagnosed post mortem. Aspergillus serology and antigen explorations were conducted respectively in 202 and 182 patients and were positive in 31% and 33%. The presence of antibodies appears to be a good prognostic factor compared with the presence of antigens. CONCLUSION: Biological diagnosis of FFI relies on the multiplicity of examinations and renewal of mycological sampling.