Characteristic and clinical relevance of Candida mannan test in the diagnosis of probable invasive candidiasis.

The gold standard laboratory tests used to diagnose invasive Candida infection (ICI) are based on the in vitro culture of blood or samples from other sterile sites. However, these tests have limited sensitivity (Se) and are generally not diagnostic until late in the infectious process. The Serion Candida mannan kit was evaluated for the diagnosis of ICI at Grenoble University Hospital (France) between 2007 and 2011. The results were then compared with worldwide data published between 1997 and 2011. This retrospective study was based on follow-up from the investigation of 162 patients of whom 91 had proven ICI; 13 had Candida colonization index (CCI) scores ≥0.42, positive mannan tests, with nonconcomitant infections; and 58 had no evidence of Candida infection. Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis were the etiologic agents in 104 patients. For patients with or without ICI, the 12-week mortality rates were 35/104 (33.7%) and 6/58 (10.3%), respectively. The mannan diagnostic specificity was 51% and Se was 77%. However, in the meta-analysis (n = 1,536), values were 86% and 62%, respectively. Positive mannan test results may appear early (median 6 days) in the development of candidemia and have moderate diagnostic value for ICI, with a negative predictive value of 83%. In patients at risk of ICI with negative candidemia, the combination of Candida mannan test data with a CCI score ≥0.42 may improve the diagnosis of probable ICI.

Minimum inhibitory concentrations of amphotericin B against Candida krusei isolates from a French teaching hospital laboratory: a retrospective study over 8 years.

Recent studies have shown decreased susceptibility of Candida krusei to amphotericin B (AmB), in addition to its inherent resistance to fluconazole. The susceptibility of C. krusei to AmB was studied in the Parasitology-Mycology laboratory of Grenoble Teaching Hospital, France. Between 2003 and 2011, we analysed 200 C. krusei isolates from 130 patients. The isolates were mainly collected in intensive care, cardio-thoracic and cancer/haematology units. Minimum inhibitory concentrations (MICs) were determined by the E-test method. The modal MIC was 0.5 µg ml(-1); the MIC(50) and MIC(90) (MICs encompassing 50% and 90% of all isolates tested, respectively) were 0.5 µg ml(-1) and 1 µg ml(-1). The Cuzick's and Kendall's tests showed a significant increase in MIC values between 2003 and 2011 (P = 0.001 and P ≤ 0.001, respectively), regardless of age or gender. No statistical difference was reached with these tests when the first 100 or 50 data were excluded. Despite the increase observed in the first period of the study, our results confirm the low AmB MICs reported in previous studies. However, some authors have recently reported much higher MICs. This discrepancy cannot be explained by method biases and could reflect C. krusei epidemiological differences among populations.

Susceptibility of 100 filamentous fungi: comparison of two diffusion methods, Neo-Sensitabs and E-test, for amphotericin B, caspofungin, itraconazole, voriconazole and posaconazole.

We compared the E-test method to that of the Neo-Sensitabs tablet diffusion assay for evaluating the in vitro susceptibility of 100 clinical isolates of filamentous fungi (Aspergillus spp., Fusarium spp., Scedosporium spp., zygomycetes and other molds) to amphotericin B, itraconazole, voriconazole, caspofungin, and posaconazole. We determined the categorical agreement level between E-test minimum inhibitory concentrations (MIC) and tablet end-points, as opposed to the following disagreement parameters: very major error - resistant parameter (R) in E-test and susceptible (S) in tablet; major error - S by E-test and R by tablet; minor error - shifts between S and susceptible dose-dependent (S-DD) or S-DD and R. We also performed linear regression analyses and computed Pearson's correlation coefficients (R values) between the log transforms of MICs and the inhibition zone diameters of the five studied antifungal agents. For itraconazole we obtained 97% categorical agreement and R = -0.727. Categorical agreement for caspofungin and voriconazole was 96% and R =-0.821 and R = -0.789, respectively. For posaconazole the categorical agreement was 94% and R =-0.743. Amphotericin B exhibited a lower degree of agreement (76%, R = -0.672), especially in studies of Aspergillus spp. Our results suggest a potential value of the Neo-Sensitabs assay for in vitro susceptibility testing of molds to itraconazole, voriconazole, caspofungin and posaconazole, while amphotericin B exhibited an overall lower degree of agreement.

Antifungal use influences Candida species distribution and susceptibility in the intensive care unit.

OBJECTIVES: Antifungal prescription practices have changed over the last decade, and the impact of these changes is unclear. Our objective here was to evaluate the effect of antifungal drug use on the distribution and drug susceptibility of Candida spp. in a French intensive care unit (ICU). METHODS: Antifungal drug use was measured as the number of defined daily doses per 1000 hospital days (DDDs/1000HD). The distribution of Candida spp. over a 6 year period (2004-09) and the MICs of antifungal drugs over 2007-09 were determined. Statistical analyses were performed to assess relationships between antifungal drug use, Candida spp. distribution and MIC changes over time. RESULTS: Of 26,450 samples from 3391 patients, 1511 were positive for Candida spp. Candida albicans predominated (52.5%), followed by Candida glabrata (16.6%) and Candida parapsilosis (7.5%). C. parapsilosis increased significantly, from 5.7% in 2004 to 12.5% in 2009 (P = 0.0005). Caspofungin use increased significantly between 2004 (17.9 DDDs/1000HD) and 2009 (69.9 DDDs/1000HD) (P < 0.0001). Between 2007 and 2009, the increase in caspofungin use correlated significantly with the increase in caspofungin MICs displayed by C. parapsilosis (P < 0.0001) and C. glabrata (P = 0.03). Amphotericin B consumption changed over time and correlated with an increase in amphotericin B MICs for C. albicans (P = 0.0002) and C. glabrata (P = 0.0005). Significant declines occurred in both fluconazole use (P < 0.0001) and fluconazole MICs of C. albicans (P < 0.001) CONCLUSIONS: Antifungal drug use in the ICU is associated with major changes in the distribution and drug susceptibility of Candida spp.

Severe filamentous fungal infections after widespread tissue damage due to traumatic injury: six cases and review of the literature.

We describe 6 cases of severe filamentous fungal infections after widespread tissue damage due to traumatic injury in previously healthy people. Additionally, we report 69 cases from an exhaustive 20-y review of the literature to investigate the epidemiological and clinical features, the prognosis and the therapeutic management of these post-traumatic severe filamentous fungal infections. Traffic (41%) and farm accidents (25%) were the main causes of injury, which involved either the limbs only (41%) or multiple sites (41%). Necrosis was the main symptom (60%) and Mucorales (72%) and Aspergillus (11%) were the 2 most frequent fungi causing infection. These infections required substantial surgical debridement or amputation (96%) associated with aggressive antifungal therapy (81%), depending on the responsible fungi. This study underlines the need for early, repeated and systematic mycological wound samples to guide and adapt surgical and antifungal management in these filamentous fungal infections.

Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered from treated patients.

Two-hundred sequential Aspergillus fumigatus isolates recovered from 26 immunocompromised patients with invasive aspergillosis or bronchial colonization were tested for their in vitro susceptibility to posaconazole, itraconazole, voriconazole, terbinafine and amphotericin B. Twenty-one patients were treated with amphotericin B and/or itraconazole. Antifungal susceptibilities of the isolates recovered before treatment were not significantly different from those of isolates recovered after the onset of antifungal therapy. The highest MICs were 0.125, 0.5, 0.5, 1 and 1 microg ml(-1) for posaconazole, itraconazole, voriconazole, terbinafine and amphotericin B, respectively. It is concluded that the emergence of resistance in A. fumigatus during antifungal therapy with amphotericin B or itraconazole is an uncommon phenomenon.

Seven-year surveillance of nosocomial invasive aspergillosis in a French University Hospital.

OBJECTIVES: This study aims at describing the evolution of the epidemiology of invasive aspergillosis (IA) in a French University Hospital focussing on nosocomial cases, in order to assess the efficiency of the environmental preventive measures which were implemented. METHODS: From 2003 to 2009, IA cases were reviewed monthly and classified according to the EORTC/MSG criteria and the origin of contamination. RESULTS: Five proven and 65 probable IA cases were diagnosed. Most of the cases (74.3%) occurred in patients with haematological malignancies. Incidences of IA and nosocomial IA (NIA) were 0.106 and 0.032 cases per 1000 admissions, respectively. All the 21 NIA cases occurred in the absence of air treatment (laminar air flow facilities or Plasmair decontamination units) and/or during construction works. The 3-month and 1-year overall survival rates were 50.6% [38.2-61.7] and 31.1% [20-42.9] respectively, and did not differ according to the origin of contamination. CONCLUSION: Nosocomial IA still accounted for a third of all IA cases diagnosed from 2003 to 2009 and mainly occurred in the absence of environmental protective measures, which were confirmed to be effective when applied. Our results show that extension and/or reinforcement of these measures is needed, especially in the haematology unit and during construction works.

Mobile air-decontamination unit and filamentous fungal load in the hematology ward: how efficient at the low-activity mode?

Air treatment with a mobile Plasmair air-decontamination unit significantly reduces the fungal spore load in hematology wards. We report that this system used at a low aspiration flow does not perform total biodecontamination against filamentous fungi. Moreover, the filamentous fungus load remaining in rooms equipped with this mobile air-decontamination unit is lowest in wards in which other preventive measures against nosocomial filamentous fungal infections are implemented.

Influence of internal and outdoor factors on filamentous fungal flora in hematology wards.

BACKGROUND: Nosocomial invasive filamentous fungi infections could result from inhalation of filamentous fungi conidia present in hospital environment. METHODS: The environmental fungal flora in 3 different hospital wards with similar air conditioning was prospectively studied during 30 months and compared to internal (presence of agranulocytosis patient, behavioral practices, activity, cleaning work) and outdoor factors (meteorologic data, outdoor fungi). The general preventive measures differed from one unit to another. RESULTS: The hematology wards with filamentous fungi preventive measures were significantly less contaminated than a conventional ward without specific measures. Internal and outdoor factors influenced the level of fungal flora. However, the influence of internal factors was greater in the conventional ward than in hematology wards. The variation of flora in the hospital environment was seasonal, and the level of this contamination in each ward was influenced by the meteorology. However, outdoor factors more readily explain the variations of fungal load in hematology than in the conventional ward. CONCLUSION: This study highlights that specific preventive measures participate significantly in the control of the filamentous fungal flora intensity due to internal factors but not those due to outdoor factors, stressing the importance of high-efficiency particulate air filtration in high-risk units.

Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis.

The effectiveness of galactomannan detection with the Platelia test was evaluated in a prospective study of 3,327 sera from 807 patients. The specificity was 99.6% (748 of 751 cases). For the groups of patients with proven and probable invasive aspergillosis, the sensitivity was 50.0% (17 of 34 cases). The disappointing sensitivity associated with the presence of rare false-positive cases underlines the limits of this test.