RESUMEN

Antifungal susceptibility testing (AST) is crucial in clinical settings to guide appropriate therapy. Nevertheless, discrepancies between treatment response and some results still persist, particularly in detecting resistance to amphotericin B (AMB) in Clavispora (Candida) lusitaniae. This study aimed to assess the susceptibility patterns of 48 recent isolates of C. lusitaniae to 9 antifungal agents and explore the feasibility of using a CLSI reference-based method to identify AMB resistance. Microdilution techniques revealed a wide range of minimal inhibitory concentration (MIC) values for azole antifungals, while echinocandins and AMB exhibited a narrow range of MIC values, with all strains considered wild-type for the tested polyene and echinocandins. However, when agar diffusion (ellipsometry) was employed for AST, certain strains displayed colonies within the inhibition ellipse, indicating potential resistance. Interestingly, these strains did not respond to AMB treatment and were isolated during AMB treatment (breakthrough). Moreover, the evaluation of AMB minimum fungicidal concentrations (MFCs) indicated that only the strains with colonies inside the ellipse had MFC/MIC ratios ≥ 4, suggesting reduced fungicidal activity. In conclusion, this study confirms the effectiveness of ellipsometry with RPMI-1640 2% glucose agar for detecting AMB resistance in C. lusitaniae. Additionally, the proposed approach of culturing "clear" wells in the microdilution method can aid in uncovering resistant strains. The findings highlight the importance of appropriate AST methods to guide effective treatment strategies for deep-seated candidiasis caused by C. lusitaniae. Further collaborative studies are warranted to validate these findings and improve the detection of AMB clinical resistance.

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Abstract Scedosporium/Lomentospora species are widely distributed in nature. They are gen-erally saprophytes, but can cause opportunistic infections in immunocompromised patients and occasionally in immunocompetent patients that are difficult to treat due to high lev-els of antifungal resistance. The distribution of Scedosporium/Lomentospora species shows regional differences. Scedosporium boydii and Scedosporium apiospermum are the most fre-quently isolated species in our region, whereas Scedosporium aurantiacum is more common in other regions. We describe the first isolation in Argentina of S. aurantiacum in a vitreous humor infection from a previously healthy patient after traumatic injury in her left eye. Due to the suspicion of fungal endophthalmitis, a mycological study of the vitreous humor was performed. The culture allowed the isolation of S. aurantiacum. The patient was treated with voriconazole with favorable clinic evolution.

Resumen Las especies de Scedosporium/Lamentospora se encuentran ampliamente distribuidas en la naturaleza. En general son saprofitas, pero pueden causar infecciones oportunistas de difícil tratamiento debido a sus altos niveles de resistencia a los antifúngicos en individuos inmunocomprometidos y, ocasionalmente, en personas inmunocompetentes. La distribución de las especies de Scedosporium/Lamentospora muestra diferencias regionales. Scedosporium boydii y S. apiospermum son las especies más frecuentemente aisladas en nuestra región, mientras que en otras S. aurantiacum es más común. Presentamos el primer aislamiento en Argentina de S. aurantiacum de una infección de humor vítreo de un paciente previamente sano que sufrió una lesión traumática. El paciente fue tratado con voriconazol y tuvo una evolución clínica favorable.

RESUMEN

Scedosporium/Lomentospora species are widely distributed in nature. They are generally saprophytes, but can cause opportunistic infections in immunocompromised patients and occasionally in immunocompetent patients that are difficult to treat due to high levels of antifungal resistance. The distribution of Scedosporium/Lomentospora species shows regional differences. Scedosporium boydii and Scedosporium apiospermum are the most frequently isolated species in our region, whereas Scedosporium aurantiacum is more common in other regions. We describe the first isolation in Argentina of S. aurantiacum in a vitreous humor infection from a previously healthy patient after traumatic injury in her left eye. Due to the suspicion of fungal endophthalmitis, a mycological study of the vitreous humor was performed. The culture allowed the isolation of S. aurantiacum. The patient was treated with voriconazole with favorable clinic evolution.

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La información sobre el uso de posaconazol en niños es escasa. Se realizó este estudio descriptivo retrospectivo entre agosto de 2010 y marzo de 2017 para evaluar las características clínicas, microbiológicas y la evolución de los pacientes tratados con posaconazol. Se incluyeron 16 niños. Mediana de edad: 161 meses (rango intercuartílico -RIC- 69-173 m). Todos tenían enfermedad subyacente y presentaban infección fúngica invasiva probada. Los aislamientos más frecuentes fueron Mucor spp. y Aspergillus spp. La dosis media de posaconazol fue 600 mg/día (400-800 mg/día) y la mediana de duración del tratamiento, 223 días (RIC 48-632). Diez pacientes presentaron efectos adversos, pero solo uno requirió suspensión del antifúngico debido a alteraciones hidroelectrolíticas.

There is limited information on the use of posaconazole in children. This retrospective and descriptive study was conducted to evaluate the clinical, microbiological characteristics and evolution of patients treated with posaconazole between August 2010 and March 2017. We included 16 children. Median age: 161 months (interquartile range -IQR-69-173m). All had underlying disease and a proven invasive fungal infection. The most frequent isolated were Mucor spp. and Aspergillus spp. The mean posaconazole dose was 600 mg /day (400-800 mg/day) and the median duration of treatment was 223 days (IQR 48-632). Ten patients had adverse effects, but only one required suspension of the antifungal treatment due to hydroelectrolytic disorders.

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There is limited information on the use of posaconazole in children. This retrospective and descriptive study was conducted to evaluate the clinical, microbiological characteristics and evolution of patients treated with posaconazole between August 2010 and March 2017. We included 16 children. Median age: 161 months (interquartile range -IQR- 69-173 m). All had underlying disease and a proven invasive fungal infection. The most frequent isolated were Mucor spp. and Aspergillus spp. The mean posaconazole dose was 600 mg/day (400-800 mg/day) and the median duration of treatment was 223 days (IQR 48-632). Ten patients had adverse effects, but only one required suspension of the antifungal treatment due to hydroelectrolytic disorders.

La información sobre el uso de posaconazol en niños es escasa. Se realizó este estudio descriptivo retrospectivo entre agosto de 2010 y marzo de 2017 para evaluar las características clínicas, microbiológicas y la evolución de los pacientes tratados con posaconazol. Se incluyeron 16 niños. Mediana de edad: 161 meses (rango intercuartílico ­RIC­ 69-173 m). Todos tenían enfermedad subyacente y presentaban infección fúngica invasiva probada. Los aislamientos más frecuentes fueron Mucor spp. y Aspergillus spp. La dosis media de posaconazol fue 600 mg/ día (400-800 mg/día) y la mediana de duración del tratamiento, 223 días (RIC 48-632). Diez pacientes presentaron efectos adversos, pero solo uno requirió suspensión del antifúngico debido a alteraciones hidroelectrolíticas.

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Trichosporon asahii es un hongo ubicuo que se ha aislado como parte de la microbiota humana. Recientemente, se ha visto una emergencia de este patógeno en infecciones tanto localizadas como sistémicas. En unidades de cuidados intensivos pediátricos para quemados, existen escasos reportes de infecciones del tracto urinario por este microorganismo. Se describen 2 pacientes pediátricos con internación prolongada por quemaduras extensas y múltiples tratamientos antibióticos previos. Ambos presentaron sepsis por infección del tracto urinario asociada a sonda vesical por Trichosporon asahii. En ambos pacientes, se realizó el recambio de la sonda vesical y tratamiento con voriconazol por 10 días, con buena evolución. En los casos presentados, debido a la ausencia de otros aislamientos microbiológicos y a la buena respuesta al tratamiento antifúngico junto con el recambio de la sonda vesical, se asumió al Trichosporon asahii como el probable agente causal de la sepsis.

Trichosporon asahii is a ubiquitous fungus that has been isolated as part of human microbiota. There has been an emergence of this pathogen in recent years, causing superficial and deep seated infections. There are scarce reports of urinary tract infections in pediatric intensive care burn units caused by this agent. We describe the cases of 2 pediatric patients with prolonged hospitalization due to severe burns that had received several antibiotic courses for previous infections. Both presented sepsis secondary to catheter related urinary tract infection by Trichosporon asahii. Both patients underwent urinary catheter replacement and were treated effectively with voriconazole for 10 days. In the cases presented, sepsis was assumed to be due to Trichosporon asahii since no other microorganism was identified and the patients showed favorable outcome with the prescribed treatment with voriconazole and replacement of the urinary catheter.

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Trichosporon asahii is a ubiquitous fungus that has been isolated as part of human microbiota. There has been an emergence of this pathogen in recent years, causing superficial and deep seated infections. There are scarce reports of urinary tract infections in pediatric intensive care burn units caused by this agent. We describe the cases of 2 pediatric patients with prolonged hospitalization due to severe burns that had received several antibiotic courses for previous infections. Both presented sepsis secondary to catheter related urinary tract infection by Trichosporon asahii. Both patients underwent urinary catheter replacement and were treated effectively with voriconazole for 10 days. In the cases presented, sepsis was assumed to be due to Trichosporon asahii since no other microorganism was identified and the patients showed favorable outcome with the prescribed treatment with voriconazole and replacement of the urinary catheter.

Trichosporon asahii es un hongo ubicuo que se ha aislado como parte de la microbiota humana. Recientemente, se ha visto una emergencia de este patógeno en infecciones tanto localizadas como sistémicas. En unidades de cuidados intensivos pediátricos para quemados, existen escasos reportes de infecciones del tracto urinario por este microorganismo. Se describen 2 pacientes pediátricos con internación prolongada por quemaduras extensas y múltiples tratamientos antibióticos previos. Ambos presentaron sepsis por infección del tracto urinario asociada a sonda vesical por Trichosporon asahii. En ambos pacientes, se realizó el recambio de la sonda vesical y tratamiento con voriconazol por 10 días, con buena evolución. En los casos presentados, debido a la ausencia de otros aislamientos microbiológicos y a la buena respuesta al tratamiento antifúngico junto con el recambio de la sonda vesical, se asumió al Trichosporon asahii como el probable agente causal de la sepsis.

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BACKGROUND: In the cases of ascitis, it is essential to determine their origin using the parameters obtained by the cytological and biochemical examinations. The aim of this study was to evaluate the usefulness of different biochemical markers and the number of cells in the differential diagnosis of ascitic fluid (AF). METHODS: One hundred ninety-one cases of AF were studied, who were admitted to the hospital from January 01, 2009 to December 31, 2014. One hundred fifty-two of them were included in the analysis, and the remaining 39 were excluded because they had more than one associated pathology, clotted or hemolyzed. RESULTS: The more frequent etiologies of AF were the cirrhosis (29%), the infections (22%) and the neoplasies (19%). Other pathologies reached 16%. Cutoff > 300 cells/mm3 detected the 78% of exudates. The AF/serum (S) of aspartate aminotransferase (AST) (> 0.5), lactate dehydrogenase (LDH) (> 0.6), proteins (PT) (> 0.5), cholesterol (COL) (> 0.4), and alanine aminotransferase (ALT) (> 0.5) correctly detected 80%, 78%, 72%, 70% and 70% of the exudates, respectively. CONCLUSION: We proposed the utilization of a new cutoff of cellular counting, major of 300/mm3, since it would allow improving the detection of exudate ascites, without including the transudate ascites. AST AF/serum ratio (AF/S) showed the major usefulness in the differentiation and characterization of AF; LDH, proteins, cholesterol and ALT might be also acceptable in the above mentioned differentiation. The serum-ascites albumin gradient (SAAG) turned out to be a good marker of portal hypertension associated with cirrhotic processes. Creatine kinase (CK), alkaline phosphatase (ALP), amylase (AMI), total bilirubin (TB), triglycerides (TG) and glucose (GLU) did not allow differentiating exudates from transudates.

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El objetivo de este trabajo fue determinar la variabilidad biológica (VB) de Aldolasa (ALD) en individuos sanos, el índice de individualidad (II) del analito y evaluar la utilidad del intervalo de referencia poblacional (IRP) considerando al IRP de los analitos útil cuando el II es > 1,4 y de poca utilidad si es <0,6. También se evaluó el valor de referencia para el cambio (VRC) en la interpretación de dos determinaciones seriadas del mismo individuo, especialmente en el seguimiento de enfermedades músculo-esqueléticas en las que los niveles de creatinquinasa (CK) permanecen dentro del intervalo de referencia, mientras que los de ALD están elevados. Se obtuvieron 8 muestras de sangre de 10 individuos aparentemente sanos en días diferentes según protocolo preestablecido. Se determinó la actividad de ALD por método enzimático UV y se calcularon los parámetros de VB, II y VRC. Se obtuvo una VB intraindividual: 31%; VB interindividual: 21%, II 1.47 y VRC 90%. De acuerdo a los coeficientes de VB y el II obtenidos, los IRP son útiles para la interpretación de los resultados de ALD. Un resultado seriado será estadísticamente diferente del dato previo cuando el mismo tenga una diferencia mayor al 90% en relación al valor previo. El VRC entre dos determinaciones seriadas debe ser calculado en cada laboratorio con su propia variabilidad analítica para una correcta interpretación de los resultados.(AU)

The aim of this study was to determine the Biological Variation (BV) of Aldolase (ALD) in healthy patients, the individuality index (II) of the analyte and to assess how useful the population reference interval (PRI) is for the interpretation of the results, considering PRI useful when the II is >1.40 and useless when it is <0.6. Reference change values (RCV) were also assessed in the interpretation of two serial measurements of the same individual, specially in the monitoring of patients in which the serum level of Creatine Kinase (CK) remain within the reference range while ALD values are increased. Eight bloodsam-ples were obtained from ten apparently healthy subjects in different days according to a predetermined protocol. ALD activity was measured by an enzymatic UV method and BV, II and RCV were calculated. Intraindividual BV was 31 %, interindividual BV 21 %, II 1.47 and RCV 90%. Based on the results obtained for BV and II, PRIs are useful for the interpretation of ADL results. A serial result will be statistically different from the previous one when the variability between both results is higher than 90%. RCV must be determined in each laboratory using their own analytical variability in order to obtain a correct interpretation of the results.(AU)

O objetivo deste trabalho foi determinar a variabilidade biológica (VB) de Aldolase (ALD) em individuos saudáveis, o índice de individualidade (II) do analito e avaliar a utilidade do intervalo de referencia populacional (IRP) considerando o IRP dos analitos útil quando o II é > 1,4 e de pouca utilidade se é <0,6. Também foi avaliado o valor de referencia da variagáo (VRV) na interpretagáo de duas determinagóes seriadas do mesmo individuo, especialmente no seguimento de doengas músculo-esqueléticas nas quais os níveis de creatinoquinase (CK) permanecem dentro do intervalo de referencia, enquanto que os de ALD estáo elevados. Foram obtidas 8 amostras de sangue de 10 individuos aparentemente saudáveis em dias diferentes conforme protocolo preestabelecido. Determinou-se a atividade de ALD por método enzimático UV e se calcularam os parámetros de VB, II e VRC. Foi obtida uma VB intra-individual: 31 %; VB interindividual: 21 %, II 1.47 e VRV 90%. De acordo com os coeficientes de VB e o II obtidos, os IRP sáo úteis para a interpretagáo dos resultados de ALD. Um resultado seriado será estatisticamente diferente do dado prévio quando o mesmo tenha uma diferenga maior a 90% em relagáo ao valor prévio. O VRV entre duas determinagóes seriadas deve ser calculado em cada laboratório com sua própria variabilidade analítica para uma correta interpretagáo dos resultados.(AU)

RESUMEN

El objetivo de este trabajo fue determinar la variabilidad biológica (VB) de Aldolasa (ALD) en individuos sanos, el índice de individualidad (II) del analito y evaluar la utilidad del intervalo de referencia poblacional (IRP) considerando al IRP de los analitos útil cuando el II es > 1,4 y de poca utilidad si es <0,6. También se evaluó el valor de referencia para el cambio (VRC) en la interpretación de dos determinaciones seriadas del mismo individuo, especialmente en el seguimiento de enfermedades músculo-esqueléticas en las que los niveles de creatinquinasa (CK) permanecen dentro del intervalo de referencia, mientras que los de ALD están elevados. Se obtuvieron 8 muestras de sangre de 10 individuos aparentemente sanos en días diferentes según protocolo preestablecido. Se determinó la actividad de ALD por método enzimático UV y se calcularon los parámetros de VB, II y VRC. Se obtuvo una VB intraindividual: 31%; VB interindividual: 21%, II 1.47 y VRC 90%. De acuerdo a los coeficientes de VB y el II obtenidos, los IRP son útiles para la interpretación de los resultados de ALD. Un resultado seriado será estadísticamente diferente del dato previo cuando el mismo tenga una diferencia mayor al 90% en relación al valor previo. El VRC entre dos determinaciones seriadas debe ser calculado en cada laboratorio con su propia variabilidad analítica para una correcta interpretación de los resultados.

The aim of this study was to determine the Biological Variation (BV) of Aldolase (ALD) in healthy patients, the individuality index (II) of the analyte and to assess how useful the population reference interval (PRI) is for the interpretation of the results, considering PRI useful when the II is >1.40 and useless when it is <0.6. Reference change values (RCV) were also assessed in the interpretation of two serial measurements of the same individual, specially in the monitoring of patients in which the serum level of Creatine Kinase (CK) remain within the reference range while ALD values are increased. Eight bloodsam-ples were obtained from ten apparently healthy subjects in different days according to a predetermined protocol. ALD activity was measured by an enzymatic UV method and BV, II and RCV were calculated. Intraindividual BV was 31 %, interindividual BV 21 %, II 1.47 and RCV 90%. Based on the results obtained for BV and II, PRIs are useful for the interpretation of ADL results. A serial result will be statistically different from the previous one when the variability between both results is higher than 90%. RCV must be determined in each laboratory using their own analytical variability in order to obtain a correct interpretation of the results.

O objetivo deste trabalho foi determinar a variabilidade biológica (VB) de Aldolase (ALD) em individuos saudáveis, o índice de individualidade (II) do analito e avaliar a utilidade do intervalo de referencia populacional (IRP) considerando o IRP dos analitos útil quando o II é > 1,4 e de pouca utilidade se é <0,6. Também foi avaliado o valor de referencia da variagáo (VRV) na interpretagáo de duas determinagóes seriadas do mesmo individuo, especialmente no seguimento de doengas músculo-esqueléticas nas quais os níveis de creatinoquinase (CK) permanecem dentro do intervalo de referencia, enquanto que os de ALD estáo elevados. Foram obtidas 8 amostras de sangue de 10 individuos aparentemente saudáveis em dias diferentes conforme protocolo preestabelecido. Determinou-se a atividade de ALD por método enzimático UV e se calcularam os parámetros de VB, II e VRC. Foi obtida uma VB intra-individual: 31 %; VB interindividual: 21 %, II 1.47 e VRV 90%. De acordo com os coeficientes de VB e o II obtidos, os IRP sáo úteis para a interpretagáo dos resultados de ALD. Um resultado seriado será estatisticamente diferente do dado prévio quando o mesmo tenha uma diferenga maior a 90% em relagáo ao valor prévio. O VRV entre duas determinagóes seriadas deve ser calculado em cada laboratório com sua própria variabilidade analítica para uma correta interpretagáo dos resultados.

Asunto(s)

RESUMEN

El objetivo de este trabajo fue determinar la variabilidad biológica (VB) de Aldolasa (ALD) en individuos sanos, el índice de individualidad (II) del analito y evaluar la utilidad del intervalo de referencia poblacional (IRP) considerando al IRP de los analitos útil cuando el II es > 1,4 y de poca utilidad si es <0,6. También se evaluó el valor de referencia para el cambio (VRC) en la interpretación de dos determinaciones seriadas del mismo individuo, especialmente en el seguimiento de enfermedades músculo-esqueléticas en las que los niveles de creatinquinasa (CK) permanecen dentro del intervalo de referencia, mientras que los de ALD están elevados. Se obtuvieron 8 muestras de sangre de 10 individuos aparentemente sanos en días diferentes según protocolo preestablecido. Se determinó la actividad de ALD por método enzimático UV y se calcularon los parámetros de VB, II y VRC. Se obtuvo una VB intraindividual: 31%; VB interindividual: 21%, II 1.47 y VRC 90%. De acuerdo a los coeficientes de VB y el II obtenidos, los IRP son útiles para la interpretación de los resultados de ALD. Un resultado seriado será estadísticamente diferente del dato previo cuando el mismo tenga una diferencia mayor al 90% en relación al valor previo. El VRC entre dos determinaciones seriadas debe ser calculado en cada laboratorio con su propia variabilidad analítica para una correcta interpretación de los resultados.(AU)

The aim of this study was to determine the Biological Variation (BV) of Aldolase (ALD) in healthy patients, the individuality index (II) of the analyte and to assess how useful the population reference interval (PRI) is for the interpretation of the results, considering PRI useful when the II is >1.40 and useless when it is <0.6. Reference change values (RCV) were also assessed in the interpretation of two serial measurements of the same individual, specially in the monitoring of patients in which the serum level of Creatine Kinase (CK) remain within the reference range while ALD values are increased. Eight bloodsam-ples were obtained from ten apparently healthy subjects in different days according to a predetermined protocol. ALD activity was measured by an enzymatic UV method and BV, II and RCV were calculated. Intraindividual BV was 31 %, interindividual BV 21 %, II 1.47 and RCV 90%. Based on the results obtained for BV and II, PRIs are useful for the interpretation of ADL results. A serial result will be statistically different from the previous one when the variability between both results is higher than 90%. RCV must be determined in each laboratory using their own analytical variability in order to obtain a correct interpretation of the results.(AU)

O objetivo deste trabalho foi determinar a variabilidade biológica (VB) de Aldolase (ALD) em individuos saudáveis, o índice de individualidade (II) do analito e avaliar a utilidade do intervalo de referencia populacional (IRP) considerando o IRP dos analitos útil quando o II é > 1,4 e de pouca utilidade se é <0,6. Também foi avaliado o valor de referencia da variagáo (VRV) na interpretagáo de duas determinagóes seriadas do mesmo individuo, especialmente no seguimento de doengas músculo-esqueléticas nas quais os níveis de creatinoquinase (CK) permanecem dentro do intervalo de referencia, enquanto que os de ALD estáo elevados. Foram obtidas 8 amostras de sangue de 10 individuos aparentemente saudáveis em dias diferentes conforme protocolo preestabelecido. Determinou-se a atividade de ALD por método enzimático UV e se calcularam os parámetros de VB, II e VRC. Foi obtida uma VB intra-individual: 31 %; VB interindividual: 21 %, II 1.47 e VRV 90%. De acordo com os coeficientes de VB e o II obtidos, os IRP sáo úteis para a interpretagáo dos resultados de ALD. Um resultado seriado será estatisticamente diferente do dado prévio quando o mesmo tenha uma diferenga maior a 90% em relagáo ao valor prévio. O VRV entre duas determinagóes seriadas deve ser calculado em cada laboratório com sua própria variabilidade analítica para uma correta interpretagáo dos resultados.(AU)