Invasive cutaneous Neoscytalidium infections in renal transplant recipients: a series of five cases.

BACKGROUND: Neoscytalidium species (formerly Scytalidium species) are black fungi that usually cause cutaneous infections mimicking dermatophytes lesions. Very few publications have reported invasive or disseminated infections. CASE PRESENTATION: In this paper, we report the clinical presentations, treatments and outcomes of five cases of invasive Neoscytalidium infections with cutaneous involvement, including two cases with disseminated infection, in five renal transplant recipients. To our knowledge, this is the first report of a series-albeit small-of renal transplant patients in whom this infection was identified. All cases occurred in a single hospital in Paris, France, between 2001 and 2011. Patients all originate from tropical area. CONCLUSION: Treatments of Neoscytalidium infection varied greatly, underlining the lack of a recommendation for a standardized treatment. All patients were cured after long-term antifungal therapy and/or surgical excision. Interestingly, one patient with disseminated infection involving the left elbow, the right leg, the lungs and the nasal septum was cured by medical therapy only without surgery. This may suggest that in contrast to others mycoses (such as mucormycosis), an adequate medical treatment could be sufficient for treating Neoscytalidium. We also point out the difficulties we had in diagnosing two patients with Kaposi's sarcoma because of the similarity of the lesions. Furthermore, our report underlines the need to check for this rare infection in immunocompromised kidney transplant recipients originating from tropical areas.

Breakthrough invasive mould infections in patients treated with caspofungin.

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.

Rapid species diagnosis for invasive candidiasis using mass spectrometry.

BACKGROUND: Matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF-MS) allows the identification of most bacteria and an increasing number of fungi. The potential for the highest clinical benefit of such methods would be in severe acute infections that require prompt treatment adapted to the infecting species. Our objective was to determine whether yeasts could be identified directly from a positive blood culture, avoiding the 1-3 days subculture step currently required before any therapeutic adjustments can be made. METHODOLOGY/PRINCIPAL FINDINGS: Using human blood spiked with Candida albicans to simulate blood cultures, we optimized protocols to obtain MALDI TOF-MS fingerprints where signals from blood proteins are reduced. Simulated cultures elaborated using a set of 12 strains belonging to 6 different species were then tested. Quantifiable spectral differences in the 5000-7400 Da mass range allowed to discriminate between these species and to build a reference database. The validation of the method and the statistical approach to spectral analysis were conducted using individual simulated blood cultures of 36 additional strains (six for each species). Correct identification of the species of these strains was obtained. CONCLUSIONS/SIGNIFICANCE: Direct MALDI TOF-MS analysis of aliquots from positive blood cultures allowed rapid and accurate identification of the main Candida species, thus obviating the need for sub-culturing on specific media. Subsequent to this proof-of-principle demonstration, the method can be extended to other clinically relevant yeast species, and applied to an adequate number of clinical samples in order to establish its potential to improve antimicrobial management of patients with fungemia.

Aspergillus flavus brain abscesses associated with hepatic amebiasis in a non-neutropenic man in Senegal.

A non-neutropenic man living in Senegal was repatriated to France for liver amebic abscesses associated with brain abscesses presumed to be of amebic origin. Surprisingly, the post-mortem examinations of brain abscesses showed Aspergillus flavus. The route of infection by A. flavus in this particular context is discussed.

MALDI-TOF MS-based drug susceptibility testing of pathogens: the example of Candida albicans and fluconazole.

MALDI-TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institute's reference method. This proof-of-concept demonstration highlights the potential for this approach to test other pathogens.

[Prevention of fungal infections related to the water supply in French hospitals: proposal for standardization of methods]. / Surveillance mycologique de l'eau pour la prévention des mycoses invasives dans les établissements de santé: propositions de standardisation des méthodologies.

OBJECTIVES: The aims of this study were to assess the risk of fungal infections related to the water supply in several hospitals and to clarify the appropriate methodology in order to standardize the technical conditions of the controls and develop guidelines. It was conducted in 10 university hospital centers across the country from February 2004 through March 2005. METHOD: A preliminary study allowed us to optimize the mycological analysis. The study was conducted under the same conditions as for bacteriological controls: water filtration through a cellulose acetate membrane cultured on agar. Departments with the highest patient risk were selected, including hematology, organ transplantation, and burn units. We selected 98 sites and sampled both water and water-related surfaces at each: three one-liter water samples (the first flow, cold and hot water) and two or three surface samples (inside the tap, pommel of the shower and siphon). At each site, a form was filled to specify its location in the unit, any water treatment (chlorine or other), filtering, and temperature. Water from taps equipped with sterilized filtration was sampled without the filter. RESULTS: There was a significant difference (p=0.039) in the number of positive cultures between the three types of water sampled: hot water (>50 degrees C) was colonized less often than first flow or cold water. Only 4% of the hot-water samples had positive cultures, compared to the 52% of the cold-water samples. Except in two hospitals with generalized contamination of the water pipes (one with Exophiala spp and the other with Fusarium spp), colonization was usually slight. Cold water was more colonized than hot water, but 79% of the samples yielded fewer than 5CFU/L. Dematiaceous hyphomycetes were isolated; Aspergillus spp were rare. The number of CFU in surface samples (that is, biofilms) was higher (mean=15 CFU per sample) but surfaces were positive less often than water (13% compared with 43% of all water samples). Sampling from siphons was productive more often than from taps (23%), but the molds isolated differed from those in the related water. Relations to bacterial flora and P. aeruginosa were also studied, together with the effects of chemical treatment. CONCLUSION: Current regulations require only bacteriological survey. The absence of knowledge about the threshold of contamination at which there is a risk of nosocomial invasive fungal infections makes it difficult to impose routine monitoring. Mycological surveys of water are required during hospital renovation, plumbing work, pipe maintenance and when air samples are negative during nosocomial infection investigations.

In vitro susceptibility to posaconazole of 1,903 yeast isolates recovered in France from 2003 to 2006 and tested by the method of the European committee on antimicrobial susceptibility testing.

The posaconazole MIC(90) for 1,903 yeast isolates from France was 1 microg/ml (range, < or =0.015 to 8 microg/ml). Ninety percent of isolates with fluconazole MICs of > or =8 microg/ml (n = 509) and 90% of those with voriconazole MICs of > or =2 microg/ml (n = 80) were inhibited by 2 and 8 microg/ml of posaconazole, respectively.

Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient.

We report a fatal case of disseminated acanthamebiasis caused by Acanthamoeba lenticulata (genotype T5) in a 39-year-old heart transplant recipient. The diagnosis was based on skin histopathologic results and confirmed by isolation of the ameba from involved skin and molecular analysis of a partial 18S rRNA gene sequence (DF3).

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series.

BACKGROUND: Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. CASE PRESENTATION: We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and aggressive symptomatic treatment. CONCLUSION: Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

Detection of Aspergillus galactomannan antigenemia to determine biological and clinical implications of beta-lactam treatments.

Detection of Aspergillus galactomannan (GM) in serum with the Platelia Aspergillus enzyme immunoassay (EIA) is useful for diagnosing invasive aspergillosis. From May 2003 to November 2004, 65 patients who did not develop aspergillosis had at least two positive sera while receiving a beta-lactam treatment (GM index [GMI], >or=0.5). Of the 69 treatment episodes scored, 41 consisted of a beta-lactam other than piperacillin-tazobactam (n=29), namely, amoxicillin-clavulanate (n=25), amoxicillin (n=10), ampicillin (n=3), or phenoxymethylpenicillin (n=2). In all cases, antigenemia became negative 24 h to 120 h upon stopping the antibiotic. Monitoring of 35 patients, including 26 with hematological malignancies, revealed three antigenemia kinetic patterns: each was observed with any drug regimen and consisted of a persistent GMI of >2.0 (65.7%), >0.5, and

A multicentre pharmacoepidemiological study of therapeutic practices in invasive fungal infections in France during 1998-1999.

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.

Susceptibility of clinical isolates of Candida lusitaniae to five systemic antifungal agents.

OBJECTIVES: The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern. METHODS: The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B. RESULTS: All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata. CONCLUSION: C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.

Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature.

Candida lusitaniae is an emerging opportunistic pathogen which exhibits an unusual antifungal susceptibility pattern. We describe a case of fatal renal infection due to C. lusitaniae in a very low birth weight neonate who was treated with short courses of fluconazole given alternately with amphotericin B. A colony morphology switching was detected on the standard primary culture medium by changes in colony size. Switching was shown to affect deeply the susceptibility to amphotericin B. Afterwards, the switched phenotype developed a cross resistance to fluconazole and itraconazole. Several issues raised by this case are discussed in the light of an extensive review of the literature. Our observations point out the importance of both the detection of colony morphology switching and the close monitoring of antifungal susceptibility in the management of infections due to C. lusitaniae. A judicious therapeutic strategy should prevent the acquisition of multidrug resistance during antifungal therapy.

Successsful voriconazole treatment of disseminated fusarium infection in an immunocompromised patient.

Fusarium infection is known to cause major morbidity and mortality in immunocompromised hosts. We report the successful treatment of disseminated Fusarium infection with skin manifestations in a severely neutropenic, immunocompromised host with voriconazole, a new second-generation triazole. Voriconazole might be an alternative therapy for patients with neutropenia who have fusariosis that is refractory or unresponsive to amphotericin B or its liposomal formulation.

[Ivermectin, a broad spectrum antiparasitic drug]. / L'ivermectine, un antiparasitaire à large spectre.

ACTIVITY: Ivermectine, derived from beta avermectines, monocyclic lactones produced by Streptomyces avermitilis, is a potent oral microfilaricide used by veterinaries since 1981. The anti-filarial activity is two-fold: both microfilaricide and embryotoxic in female adults; it has no activity on the latter. INDICATIONS: Ivermectine is the treatment of choice in onchocercosis, induced by the nematode Onchocerca volvulus, and was included in the onchocercosis control program (programme de contrôle de l'onchocercose (OCP) in 1987. Ivermectine has also demonstrated efficacy on other filaries (Wuchereria bancrofti, Loa loa), in intestinal nematodes (Ascaris lumbricoïdes, Strongyloides stercoralis) and in parasite nematodes in man (larva migrans ankylosis). ACCORDING TO THE RESULTS OF RECENT STUDIES: Its activity has been recently extended to ectoparasitosis: sarcoptes and pediculosis of the scalp.

Potential value of Plasmodium falciparum-associated antigen and antibody detection for screening of blood donors to prevent transfusion-transmitted malaria.

BACKGROUND: Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity. STUDY DESIGN AND METHODS: To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens. RESULTS: Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001). CONCLUSION: Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.