Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

Candida albicans biofilms on different materials for manufacturing implant abutments and prostheses

BACKGROUND: Morphological, physical and chemical properties of both implants and prostheses can determine the biofilm formation on their surface and increase the risk of biological complications. The aim of this study was to evaluate the capacity of biofilm formation of Candida albicans on different materials used to manufacture abutments and prostheses. MATERIAL AND METHODS: Biofilm formation was analyzed on cp grade II titanium, cobalt-chromium alloy and zirconia, silicone, acrylic resin (polymethylmethacrylate) and nano-hybrid composite. Some samples were partially covered with lithium disilicate glass ceramic to study specifically the junction areas. C. albicans was incubated in a biofilm reactor at 37 °C with agitation. The biofilm formation was evaluated at 24 and 48 hours. In addition, the morphology of the biofilm was evaluated by scanning electron microscopy. RESULTS: C. albicans developed biofilms on the surface of all materials tested. Cobalt-chromium alloy showed the lowest density of adhered biofilm, followed by zirconia and titanium. Silicone and resin showed up to 20 times higher density of biofilm. A higher biofilm formation was observed when junctions of materials presented micro-pores or imperfections. CONCLUSIONS: The biofilm formed in the three materials used in the manufacture of abutments and prostheses showed no major differences, being far less dense than in the resins. Two clinical recommendations can be made: to avoid the presence of resins in the subgingival area of implant prostheses and to design prostheses placing cobalt-chromium alloy/ceramic or titanium/ceramic junctions as far as possible from implants

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Candida albicans biofilms on different materials for manufacturing implant abutments and prostheses.

BACKGROUND: Morphological, physical and chemical properties of both implants and prostheses can determine the biofilm formation on their surface and increase the risk of biological complications. The aim of this study was to evaluate the capacity of biofilm formation of Candida albicans on different materials used to manufacture abutments and prostheses. MATERIAL AND METHODS: Biofilm formation was analyzed on cp grade II titanium, cobalt-chromium alloy and zirconia, silicone, acrylic resin (polymethylmethacrylate) and nano-hybrid composite. Some samples were partially covered with lithium disilicate glass ceramic to study specifically the junction areas.C. albicans was incubated in a biofilm reactor at 37 °C with agitation. The biofilm formation was evaluated at 24 and 48 hours. In addition, the morphology of the biofilm was evaluated by scanning electron microscopy. RESULTS: C. albicans developed biofilms on the surface of all materials tested. Cobalt-chromium alloy showed the lowest density of adhered biofilm, followed by zirconia and titanium. Silicone and resin showed up to 20 times higher density of biofilm. A higher biofilm formation was observed when junctions of materials presented micropores or imperfections. CONCLUSIONS: The biofilm formed in the three materials used in the manufacture of abutments and prostheses showed no major differences, being far less dense than in the resins. Two clinical recommendations can be made: to avoid the presence of resins in the subgingival area of implant prostheses and to design prostheses placing cobalt-chromium alloy/ceramic or titanium/ceramic junctions as far as possible from implants.

Therapeutic tools for oral candidiasis: Current and new antifungal drugs.

BACKGROUND: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. MATERIAL AND METHODS: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. RESULTS: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. CONCLUSIONS: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.

Postantifungal effect of anidulafungin against Candida albicans, Candida dubliniensis, Candida africana, Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis.

OBJECTIVE: Candida albicans remains the most common aetiology of invasive candidiasis, leading to high morbidity and mortality. Nevertheless, the incidence of candidiasis due to non-C. albicans species, such as Candida parapsilosis, is increasing. Postantifungal effect (PAFE) is relevant for establishing dosage schedules in antifungal therapy, as the frequency of antifungal administration could change depending on PAFE. The aim of this study was to evaluate the PAFE of anidulafungin against C. albicans, Candida dubliniensis, Candida africana, C. parapsilosis, Candida metapsilosis and Candida orthopsilosis. METHODS: Twenty-one Candida strains were evaluated. Cells were exposed to anidulafungin for 1 h at concentrations ranging from 0.12 to 8 mg/L for PAFE studies. Time-kill experiments (TK) were conducted at the same concentrations. The experiments were performed using an inoculum of 1-5 x 105 cells/mL and 48 h incubation. Readings of PAFE and TK were done at 0, 2, 4, 6, 24 and 48 h. RESULTS: Anidulafungin was fungicidal against 2 out of 14 (14%) strains of C. albicans related species in PAFE experiments. Moreover, 2 mg/L of anidulafungin exerted a prolonged PAFE (≥ 33.6 h) against 13 out of 14 (93%) strains. Similarly, fungicidal endpoint was achieved against 1 out of 7 (14%) strains of C. parapsilosis complex, being PAFE prolonged (≥ 42 h) against 6 out of 7 (86%) strains. CONCLUSIONS: Anidulafungin induced a significant and prolonged PAFE against C. albicans and C. parapsilosis and their related species.

Method-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in Candida and Aspergillus Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion Methods.

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.

Impact of a multifaceted educational intervention including serious games to improve the management of invasive candidiasis in critically ill patients / Impacto de una intervención educacional múltiple incluyendo juegos interactivos para la mejora del manejo de la candidiasis invasiva en pacientes críticos

OBJECTIVES: Infections caused by Candida species are common in critically ill patients and contribute to significant morbidity and mortality. The EPICO Project (Epico 1 and Epico 2.0 studies) recently used a Delphi approach to elaborate guidelines for the diagnosis and treatment of this condition in critically ill adult patients. We aimed to evaluate the impact of a multifaceted educational intervention based on the Epico 1 and Epico 2.0 recommendations. DESIGN: Specialists anonymously responded to two online surveys before and after a multifaceted educational intervention consisting of 60-min educational sessions, the distribution of slide kits and pocket guides with the recommendations, and an interactive virtual case presented at a teleconference and available for online consultation. SETTING: A total of 74 Spanish hospitals. PARTICIPANTS: Specialists of the Intensive Care Units in the participating hospitals. Variables of interest: Specialist knowledge and reported practices evaluated using a survey. The McNemar test was used to compare the responses in the pre- and post-intervention surveys. RESULTS: A total of 255 and 248 specialists completed both surveys, in both periods, respectively. The pre-intervention surveys showed many specialists to be unaware of the best approach for managing invasive candidiasis. After both educational interventions, specialist knowledge and reported practices were found to be more in line with nearly all the recommendations of the Epico 1 and Epico 2.0 guidelines, except as regards de-escalation from echinocandins to fluconazole in Candida glabrata infections (p = 0.055), and the duration of antifungal treatment in both candidemia and peritoneal candidiasis. CONCLUSIONS: This multifaceted educational intervention based on the Epico Project recommendations improved specialist knowledge of the management of invasive candidiasis in critically ill patients

OBJETIVOS: Las infecciones por Candida son frecuentes en los pacientes críticos y conllevan un incremento de la morbimortalidad. Nuestro objetivo es evaluar el impacto de una intervención educativa múltiple fundamentados en las recomendaciones de los proyectos basados en metodología Delphi Epico 1 y Epico 2.0. DISEÑO: Especialistas respondieron anónimamente 2 cuestionarios a través de Internet antes y después de una intervención educativa múltiple que consistió en: sesiones educativas de 60min, distribución de kits de diapositivas y guías de bolsillo, y un caso virtual interactivo presentado en una teleconferencia y disponible para su consulta a través de Internet. Ámbito: Setenta y cuatro hospitales españoles. PARTICIPANTES: Especialistas de las unidades de cuidados intensivos de los hospitales participantes. Variables de interés: Conocimientos y práctica clínica valorada a través de un cuestionario. El test de McNemar se empleó para comparar las respuestas entre los periodos pre y postintervención. RESULTADOS: Un total de 255 y 248 especialistas completaron ambos cuestionarios en los 2 periodos, respectivamente. Los cuestionarios preintervención mostraron que muchos especialistas desconocían el mejor tratamiento de la candidiasis invasiva. Después de las 2 intervenciones educativas, el conocimiento de los especialistas y las prácticas reportadas estaban más próximos a las recomendaciones de las guías Epico 1 y 2.0, excepto para el desescalado de equinocandinas a fluconazol en las infecciones por C. glabrata (p = 0,055) y en la duración del tratamiento antifúngico en la candidemia y en la peritonitis candidiásica. CONCLUSIONES: Esta intervención educativa múltiple basada en las recomendaciones del proyecto EPICO mejoró el conocimiento de los profesionales acerca del manejo de la candidiasis invasiva en el paciente crítico

Impact of a multifaceted educational intervention including serious games to improve the management of invasive candidiasis in critically ill patients.

OBJECTIVES: Infections caused by Candida species are common in critically ill patients and contribute to significant morbidity and mortality. The EPICO Project (Epico 1 and Epico 2.0 studies) recently used a Delphi approach to elaborate guidelines for the diagnosis and treatment of this condition in critically ill adult patients. We aimed to evaluate the impact of a multifaceted educational intervention based on the Epico 1 and Epico 2.0 recommendations. DESIGN: Specialists anonymously responded to two online surveys before and after a multifaceted educational intervention consisting of 60-min educational sessions, the distribution of slide kits and pocket guides with the recommendations, and an interactive virtual case presented at a teleconference and available for online consultation. SETTING: A total of 74 Spanish hospitals. PARTICIPANTS: Specialists of the Intensive Care Units in the participating hospitals. VARIABLES OF INTEREST: Specialist knowledge and reported practices evaluated using a survey. The McNemar test was used to compare the responses in the pre- and post-intervention surveys. RESULTS: A total of 255 and 248 specialists completed both surveys, in both periods, respectively. The pre-intervention surveys showed many specialists to be unaware of the best approach for managing invasive candidiasis. After both educational interventions, specialist knowledge and reported practices were found to be more in line with nearly all the recommendations of the Epico 1 and Epico 2.0 guidelines, except as regards de-escalation from echinocandins to fluconazole in Candida glabrata infections (p=0.055), and the duration of antifungal treatment in both candidemia and peritoneal candidiasis. CONCLUSIONS: This multifaceted educational intervention based on the Epico Project recommendations improved specialist knowledge of the management of invasive candidiasis in critically ill patients.

Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method.

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.

Validation of the PCR-dHPLC method for rapid identification of Candida glabrata phylogenetically related species in different biological matrices.

Since two new species phylogenetically related to Candida glabrata with slightly different phenotypes and antifungal susceptibility profiles have been described, it seems to be necessary from clinical point of view, to develop a rapid and accurate identification system in order to distinguish between these three fungal species. We studied the performance of denaturing high performance liquid chromatography (dHPLC) as a faster (less than 7 min) and alternative novel technique for simultaneous analysis of Candida species in different biological matrices. The analyses show the good low limit of detection (LLOD) in all biological matrices studied (5.16-9.56 ngµL(-1), 4.14-4.70 ng µL(-1) and 3.99-4.66 ng µL(-1) for Candida bracarensis, Candida nivariensis and C. glabrata, respectively). 180 Candida isolates were analyzed in order to demonstrate the method suitability for screening analysis to identify C. glabrata and its cryptic species (C. bracarensis and C. nivariensis) in clinical routine.

Antifungal activity of posaconazole against Candida spp. and non-Candida clinical yeasts isolates.

The in vitro antifungal activity of posaconazole was tested against 315 yeast clinical isolates and 11 ATCC reference strains by means an agar diffusion method (Neosensitabs, Rosco,Denmark) based in CLSI M44-A2 document. Posaconazole activity was excellent against Cryptococcus and Rhodotorula species studied and showed very good activity against most species of Candida tested. A total of 13 clinical isolates (4.1%) were resistant: Candida albicans (n=5), Candida glabrata (n=5), Candida tropicalis (n=1), Geotrichum australiensis (n=1) and Geotrichum capitatum (n=1). Our results suggest posaconazole is an effective antifungal agent against the most clinically important yeasts species (92.7% of susceptibility). Agar diffusion method provides good conditions for the posaconazole susceptibility study in the routine laboratory.

Clinical significance of the detection of Candida albicans germ tube-specific antibodies in critically ill patients.

The present study, comprising a prospective multicentre study including 53 non-neutropenic patients from intensive care units (ICU) in six Spanish tertiary-care hospitals, was carried out to determine the clinical significance and influence on mortality of Candida albicans germ tube-specific antibodies (CAGTA). There were 22 patients (41.5%) for whom the CAGTA results were positive, although none of had a blood culture positive for Candida. The intra-ICU mortality rate was significantly lower (p = 0.004) in CAGTA-positive patients (61.2% vs. 22.7%). Multivariate analysis confirmed that a positive CAGTA result was the only protective factor to be independently associated with ICU mortality (beta coefficient = -0.3856; 95% confidence interval = -0.648 to -0.123).

Activity of caspofungin and voriconazole against clinical isolates of Candida and other medically important yeasts by the CLSI M-44A disk diffusion method with Neo-Sensitabs tablets.

In vitro activity of caspofungin and voriconazole against 184 clinical isolates of Candida and other medically important yeasts in comparison with that of fluconazole, ketoconazole, itraconazole and amphotericin B was determined by using a disk diffusion method (Neo-Sensitabs) standardized according to the recommendations of the CLSI documents M44-A and M44-S1 (same medium: Mueller-Hinton plus methylene blue; inoculum and minimal inhibitory concentration/zone breakpoints). Seventy-two percent of clinical isolates were susceptible to caspofungin, 23.6% showed an intermediate susceptibility (most of them were Candida parapsilosis) and 4.3% were resistant (values for Candida spp. were 71.2, 23.8 and 5%, respectively). For voriconazole, 96.7% of clinical isolates were susceptible and 3.3% were resistant (Candida spp.: 96 and 3.8%, respectively). Both caspofungin and voriconazole showed high activity against a wide variety of clinically important yeasts.

In vitro activity of voriconazole against dermatophytes, Scopulariopsis brevicaulis and other opportunistic fungi as agents of onychomycosis.

Using a reference microdilution method, we studied the antifungal susceptibility to voriconazole and fluconazole of 304 clinical isolates from four species of onychomycosis-causing dermatophytes, 196 isolates of dermatophytes not related to nail infection as well as Scopulariopsis brevicaulis, Fusarium spp. and Scytalidium dimidiatum. Results showed a high antifungal activity of voriconazole against dermatophytes (geometric mean minimal inhibitory concentration (MIC)=1.14 microg/mL; MIC for 50% of the organisms (MIC(50))=0.062 miccrog/mL; MIC for 90% of the organisms (MIC(90))=0.25 microg/mL). For S. brevicaulis, the in vitro activity of voriconazole was considerably lower (geometric mean MIC=8.52 microg/mL; MIC(50) and MIC(90)=16 microg/mL). Although voriconazole is not among the drugs recommended for the management of onychomycosis, it can be a useful alternative for recalcitrant infections.

Comparison of tablet and disk diffusion methods for fluconazole and voriconazole in vitro activity testing against clinical yeast isolates.

We have compared a commercially available tablet diffusion method for the in vitro antifungal susceptibility testing of fluconazole (FCZ) and voriconazole (VCZ) with the disk diffusion method M44 (CLSI) with 282 clinical yeast isolates. The superior stability of antifungal agents in tablets can explain the differences for each category of susceptibility by both methods.Neo-Sensitabs tablets antifungal susceptibility testing showed an excellent correlation (0.98 for FCZ and 0.98 for VCZ at 24h and 0.96 for FCZ and 0.94 for VCZ at 48 h ), a reduced percentage of disagreements (4.6% and 8.2% for FCZ at 24h and 48 h respectively; 1.1% and 2.1% for VCZ at 24h and 48 h respectively) and the absence of statistically significant difference in comparison with the reference protocol for performing antifungal susceptibility testing with the agar diffusion method.

Diagnostic potential of (1, 3)-beta-D-glucan and anti-Candida albicans germ tube antibodies for the diagnosis and therapeutic monitoring of invasive candidiasis in neutropenic adult patients

Se ha evaluado la utilidad de la detección dos veces por semana de Beta-glucano (BG) y de anticuerpos anti-micelio de Candida albicans (CAGT) para el diagnóstico y el seguimiento de la candidiasis invasora (CI) en 35 episodios de pacientes neutropénicos de alto riesgo. Se diagnosticaron tres casos de CI probada y tres probables. Se alcanzaron resultados positivos para ambos marcadores en el 100% de las CI probadas y en el 66% de las CI probables. La sensibilidad, especificidad, valores predictivos positivo y negativo para la detección de BG y anticuerpos contra CAGT fueron 83,3%, 89,&%, 62,5% y 96,3%, y 83,3%, 86,2%, 55,5% y 96,1%, respectivamente. El porcentaje de falsos positivos para BG y anticuerpos contra CAGT fue del 10,3% y 13,8% para la detección de BG y anticuerpos anti-CAGT, respectivamente. Sin embargo, los pacientes con resultados falsos positivos fueron diferentes para cada prueba. Ambas pruebas se anticiparon al diagnóstico clínico y radiológico, así como al inicio de la terapia antifúngica en la mayoría de los pacientes. La combinación de ambas pruebas mejoró la especificidad y el valor positivo hasta el 100%(AU)

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%(AU)