Anidulafungin versus fluconazole in the treatment of Candida albicans chorioretinitis.

BACKGROUND: Candida albicans chorioretinitis is the most common cause of endogenous fungal endophthalmitis. Echinocandins are recommended as first-line therapy in the treatment of invasive candidiasis (IC), but in clinically stable patients with IC and endophthalmitis caused by Candida species susceptible to azole compounds these are the first-line treatment due to their better intraocular penetration. CASE REPORT: A 42-year-old woman admitted to hospital for duodenal perforation after gastrointestinal surgery and treated with broad-spectrum antibiotics developed C. albicans candidemia. According to protocol, an antifungal treatment with anidulafungin was given. The patient presented no visual symptoms but on routinary ophthalmoscopic examination multiple bilateral chorioretinal lesions were observed. Systemic therapy was changed to fluconazole, with good systemic and ocular results. CONCLUSIONS: Azole compounds are the first-line therapy for endophthalmitis associated with candidemia. However, clinical guidelines often propose echinocandins as the first option for IC. In some cases, C. albicans chorioretinitis will require a change in the systemic treatment to assure better intraocular penetration. According to the current evidence and our own experience, routine funduscopy is not necessary in all IC patients. However, we do recommend fundus examination in patients with visual symptoms or those unable to report them (paediatric patients and patients with an altered level of consciousness), and in those who are being treated with echinocandins in monotherapy.

Determinación cualitativa de anidulafungina en líquidos de diálisis con administración intraperitoneal / Qualitative determination of anidulafungin in dialysis fluids with intraperitoneal administration

La infección fúngica peritoneal es poco frecuente pero supone una elevada mortalidad. A pesar de que la principal recomendación es la retirada de catéter cuando se sospecha que es éste el foco de infección, hay ocasiones en las se requiere considerar otras opciones. La administración de anidulafungina intraperitoneal es una técnica sobre la que hay pocos estudios. Presentamos un caso clínico en el que administramos anidulafungina intraperitoneal y analizamos mediante técnica cualitativa la presencia del antifúngico en distintas muestras. Además, calculamos el porcentaje de reducción de anidulafungina entre el líquido de diálisis en el que la diluimos y este mismo tras permanecer 8 horas en la cavidad peritoneal. (AU)

Peritoneal fungal infection is rare but involves high mortality. Although the main recommendation is catheter removal when it is suspected that this is the focus of infection, there are occasions when other options are required.There are few references about administration of intraperitoneal anidulafungin. We present a clinical case in which we administer intraperitoneal anidulafungin and analyze the presence of this antifungal in different samples using a qualitative technique. In addition, we calculate the percentage reduction of anidulafungin between the dialysis fluid in which we diluted it and this fluid after remain 8 hours in the peritoneal cavity. (AU)

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. METHODS: Prospective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. RESULTS: Of the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p=0.001), IC Charlson>2 (58.3% vs 38.8; p=0.053), duration of treatment (15 days vs 10.39 days; p=0.001) and patients with central catheters (54.2% vs 21.7%; p=0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p=0.45) or re-admissions (12.5% vs 10%; p=0.686) and OPAT with AT was successful in 21/24 patients (87.5%). CONCLUSIONS: AT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician.

Killing kinetics of anidulafungin, caspofungin and micafungin against Candida parapsilosis species complex: Evaluation of the fungicidal activity.

BACKGROUND: Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis are emerging as relevant causes of candidemia. Moreover, they show differences in their antifungal susceptibility and virulence. The echinocandins are different in terms of in vitro antifungal activity against Candida. Time-kill (TK) curves represent an excellent approach to evaluate the fungicidal activity of antifungal drugs. AIMS: To compare the fungicidal activities of anidulafungin, caspofungin and micafungin against C. parapsilosis species complex by TK curves. METHODS: Antifungal activities of three echinocandins against C. parapsilosis, C. metapsilosis and C. orthopsilosis were studied by TK curves. Drug concentrations assayed were 0.25, 2 and 8µg/ml. CFU/ml were determined at 0, 2, 4, 6, 24 and 48h. RESULTS: Killing activities of echinocandins were species-, isolates- and concentration-dependent. Anidulafungin reached the fungicidad endpoint for 6 out of 7 isolates (86%); it required between 13.34 and 29.67h to reach this endpoint for the three species studied, but more than 48h were needed against one isolate of C. orthopsilosis (8µg/ml). Caspofungin fungicidal endpoint was only achieved with 8µg/ml against one isolate of C. metapsilosis after 30.12h (1 out of 7 isolates; 14%). Micafungin fungicidal endpoint was reached in 12.74-28.38h (8µg/ml) against one isolate each of C. parapsilosis and C. orthopsilosis, and against both C. metapsilosis isolates (4 out of 7 isolates; 57%). CONCLUSIONS: C. metapsilosis was the most susceptible species to echinocandins, followed by C. orthopsilosis and C. parapsilosis. Anidulafungin was the most active echinocandin against C. parapsilosis complex.

Anidulafungina en niños: experiencia de un hospital pediátrico de tercer nivel en Argentina / Ánidulafungin in children: Experience in a tertiary care children's hospital in Argentina

La experiencia con anidulafungina en el tratamiento de infecciones fúngicas invasivas en pediatría es escasa. Se presenta nuestra experiencia en 55 niños. La anidulafungina se administró por vía intravenosa en la dosis de carga de 3 mg/kg en una sola dosis diaria, seguida de 1,5 mg/kg cada 24 h durante una media de 14 días (rango, 7-22 d.). La mediana de edad de los pacientes fue de 114 meses (rango intercuartíhco, 32168 m.). Todos los pacientes tenían enfermedades subyacentes. En los trasplantados de médula ósea, la diferencia entre el valor inicial y al final de la administración del fármaco en el recuento de glóbulos blancos, valores de transaminasas y función renal no fue significativo. Ninguno de los pacientes tuvo eventos adversos o murió por causas relacionadas con anidulafungina. La anidulafungina podría ser una opción para la profilaxis o el tratamiento de las infecciones fúngicas invasivas en pediatría, aunque se requieren estudios metodológicamente sólidos para probarlo.

The experience using anidulafungin for the treatment of invasive fungal infections in pediatrics is limited. In this article, we describe our experience in 55 children. Anidulafungin was administered intravenously at a loading dose of 3 mg/kg once daily, followed by 1.5 mg/kg every 24 hours over a mean period of 14 days (range: 7-22 days). Patients' median age was 114 months old (interquartile range: 32-168 months old). All patients had underlying diseases. Among patients with bone marrow transplant, the difference in white blood cell count, transaminase levels, and renal function at baseline and at the end of anidulafungin administration was not significant. No adverse events were reported and no patient died from an anidulafungin-related cause. Anidulafungin may be considered an alternative for the prophylaxis or treatment of invasive fungal infections in pediatrics but methodologically robust studies are needed to confirm this.

[Activity of amphotericin B and anidulafungin, alone and combined, against Candida tropicalis biofilms developed on Teflon® and titanium]. / Actividad de la anfotericina B y la anidulafungina, solas y combinadas, frente a biopelículas de Candida tropicalis formadas sobre Teflon® y titanio.

BACKGROUND: Current therapeutic strategies have a limited efficacy against Candida biofilms that form on the surfaces of biomedical devices. Few studies have evaluated the activity of antifungal agents against Candida tropicalis biofilms. OBJECTIVES: To evaluate the activity of amphotericin B (AMB) and anidulafungin (AND), alone and in combination, against C. tropicalis biofilms developed on polytetrafluoroethylene (teflon -PTFE) and titanium surfaces using time-kill assays. METHODS: Assays were performed using the CDC Biofilm Reactor equipped with PTFE and titanium disks with C. tropicalis biofilms after 24h of maturation. The concentrations assayed were 40mg/l for AMB and 8mg/l for AND, both alone and combined. After 24, 48 and 72h of exposure to the antifungals, the cfu/cm2 was determined by a vortexing-sonication procedure. RESULTS: AMB reduced biofilm viable cells attached to PTFE and titanium by ≥99% and AND by 89.3% on PTFE and 96.8% on titanium. The AMB+AND combination was less active than AMB alone, both on PTFE (decrease of cfu/cm2 3.09 Log10vs. 1.08 when combined) and titanium (4.51 vs. 1.53 when combined), being the interaction irrelevant on both surfaces. CONCLUSIONS: AMB is more active than AND against C. tropicalis biofilms. Yeast killing rates are higher on titanium than on PTFE surfaces. The combination of AMB plus AND is less effective than AMB alone on both surfaces.

Anidulafungina en niños: Experiencia en niños con trasplante de médula ósea / Anidulafungin in children: experience in children undergoing bone marrow transplantation

Introducción: Las infecciones fúngicas invasoras (IFI) son un problema de salud cada vez mayor, y se asocian con una alta morbilidad y mortalidad. Las nuevas opciones terapéuticas, tales como las equinocandinas y entre estos anidulafungina, se han utilizado en la población adulta, pero en pacientes pediátricos con trasplante de médula ósea la experiencia es escasa. Objetivo: El objetivo de este estudio descriptivo es presentar nuestra experiencia con el uso de la anidulafungina como profilaxis o tratamiento en pacientes con trasplante de médula ósea. Material y métodos: Entre enero hasta junio 2016, 29 pacientes trasplantados de médula ósea recibieron anidulafungina como profilaxis o tratamiento de infecciones fúngicas invasivas (IFI) probadas, probables o posibles. En todos los casos se monitorizó el valor de transaminasas, bilirrubina, creatinina y el recuento de glóbulos blancos al inicio y al final del tratamiento. Resultados: La anidulafungina se administró por vía intravenosa en una dosis de carga de 3 mg/kg/día, seguida de 1,5 mg/kg/día durante una mediana (Md) de 16 días (intervalo intercuartílico: 2-65 d). La Md de la edad de los pacientes fue de 97 meses (rango: 6-211m). La anidulafungina fue indicada como tratamiento en 7 casos (24%) y como profilaxis primaria o secundaria,en 22 (76%). En un paciente se confirmó microbiológicamente una IFI, por Candida albicans. Las Md de los parámetros bioquímicos en el inicio del tratamiento y al final, fueron: transaminasas GOT 29,5 U/l y 32 U/l (p 0,44); bilirrubina 0,35 y 0,30 mg/dL (p: 0,20); creatinina, 0,52 y 0,60 mg/dl (p:0,67). El recuento de glóbulos blancos mostró una gran variabilidad debido a la enfermedad subyacente, pero la diferencia de su valor entre el inicio y al final de la administración del fármaco, no fue significativo: Md 2810 células/mm3 y 5160 células/mm3, respectivamente (p: 0,07). Ninguno de los pacientes tuvo eventos adversos o murieron por causas relacionadas con anidulafungina. En el seguimiento a 30 días no se registró recaída de la infección o mortalidad relacionada a la droga. Conclusiones: Los resultados de nuestra serie sugieren que la anidulafungina podría ser una opción para la profilaxis o el tratamiento de las IFI en los niños con trasplante de médula ósea. Se requieren más estudios para confirmar estas observaciones (AU)

Introduction: Invasive fungal infections (IFI) are an increasing health problem associated with high morbidity and mortality. New treatment options, such as echinocandins and among these anidulafungin, have been used in the adult population, but experience in children undergoing bone marrow transplantation is scarce. Aim: The aim of this descriptive study is to present our experience with the use of anidulafungine as prophylaxis or treatment in patients undergoing bone marrow transplantation. Material and methods: Between January and June 2016, 29 patients who underwent bone marrow transplantation received anidulafungin as prophylaxis against or treatment for confirmed, probable, or possible (IFI). In all cases transaminase, bilirubin, and creatinine levels as well as total white blood cell count were monitored at treatment initiation and completion. Results: Anidulafungine is administered intravenously in a loading dose of 3 mg/kg/day, followed by 1.5 mg/kg/day for a mean of 16 days (interquartile range: 2-65 d). Mean age of the patients was 97 months (range: 6-211m). Anidulafungine was used as treatment in 7 cases (24%) and as primary or secondary prophylaxis in 22 (76%). IFI was microbiologically confirmed to be Candida albicans in one patient. Mean biochemical parameters at treatment onset and completion were: transaminases AST 29.5 U/l and 32 U/l (p 0.44); bilirubin 0.35 and 0.30 mg/dL (p 0.20); creatinine, 0.52 and 0.60 mg/dl (p : 0.67). White blood cell count was highly variable due to the underlying disease; however, the difference between values at treatment initiation and completion were not significant: Mean 2810 cells/mm3 and 5160 cells/mm3, respectively (p: 0.07). None of the patients had adverse effects or died because of anidulafungin-related causes. At 30 days of follow-up no relapse of infection or drug-related mortality was observed. Conclusions: The results in our series suggest that anidulafungin is an option for the prophylaxis against or treatment of IFI in children undergoing bone marrow transplantation. Further studies are necessary to confirm these findings (AU)

Determinação da susceptibilidade de Candida spp. de amostras de hemoculturas de pacientes atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto / Determination of the susceptibility of Candida spp. Of blood samples from patients treated at Hospital das Clínicas of the Medical School of Ribeirão Preto

Os fungos podem ser classificados como patogênicos e oportunistas. Um exemplo de oportunista é o gênero Candida spp., cujas principais espécies de interesse médico são: Candida glabrata, Candida dubliniensis, Candida krusei, Candida parapsilosis, Candida tropicalis e Candida albicans. Elas são grandes causadoras de infecção hospitalar. Existem cinco classes de antifúngicos, são eles os azólicos, as equinocandinas, os poliênicos, os análogos da pirimidina e as alilaminas. Os poliênicos são drogas que atuam na membrana da célula fúngica, um exemplo dessa classe é a Anfotericina B...

Treatment of invasive fungal disease using anidulafungin alone or in combination for hematologic patients with concomitant hepatic or renal impairment.

BACKGROUND: Invasive fungal disease (IFD) treatment is challenging in hematologic patients due to drug interactions and toxicities that limit the use of the antifungal agents. AIMS: To analyze retrospectively in terms of safety and potential efficacy anidulafungin therapy, alone or in combination. METHODS: Our institutional guidelines recommended anidulafungin treatment in hematologic patients with suspected IFD and concomitant renal or liver impairment (to avoid drug interactions and preserve organ function). RESULTS: From 2008 to 2013, 24 episodes of IFD occurring in 21 patients were classified as proven (4 cases), probable (15 cases) and possible (5 cases). Anidulafungin was administered alone (13%) or in combination (88%). Eight (33%) episodes were resolved, using monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve cases (50%) were registered as failure (death due to IFD progression in 4 patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%) were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn in any case due to toxicity. CONCLUSIONS: Anidulafungin therapy, alone or in combination, could be considered in hematologic patients with IFD and concomitant liver or renal impairment. Due to the low number of patients, we cannot draw any conclusion about efficacy.

[Susceptibility of Candida albicans blood isolates to 3 antifungal drugs: retrospective study in Rio Grande do Sul, Brazil, 1999-2009]. / Sensibilidad de aislamientos de Candida albicans de hemocultivos a 3 fármacos: estudio retrospectivo en Rio Grande do Sul, Brasil, 1999 a 2009.

BACKGROUND: Candidiasis is one of the most important among recurrent invasive yeast infections in patients, thus antifungal treatment becomes a challenge. AIMS: The aim of this study was to evaluate the in vitro activity of clinical Candida albicans isolates from blood cultures to fluconazole, amphotericin B and anidulafungin, in a hospital from Rio Grande do Sul, Brazil. METHODS: The susceptibility of 153 isolates to the 3 drugs mentioned was tested according to Clinical and Laboratory Standars Institute. Minimal inhibitory and fungicidal concentrations (MIC, MFC, respectively) of each drug were determined, as well as the epidemiological cutoff value (ECV). RESULTS: All of the isolates were susceptible to anidulafungin, MIC and MFC ≤ 1 µg/ml; however, when compared with ECV, 3% of the isolates exhibited higher values against fluconazole, 96% were susceptible, 3% susceptible dose-dependent, and 1% resistant. Also, it was observed that 21% of the isolates exhibited higher values than ECV. One isolate was resistant to amphotericin B; the other ones, susceptible, based on the MFC; furthermore, 1.5% of the isolates exhibited higher values. CONCLUSIONS: C. albicans isolates exhibited more susceptibility to anidulafungin, and 90% of them (MIC90) exhibited the lowest values against amphotericin B. Based on ECV and Pfaller classification, isolates could be resistant to fluconazole, demonstrating the importance of the combination of these parameters.

Susceptibilidad in vitro a anidulafungina en 100 cepas de especies de Candida aisladas previo a la introducción de esta equinocandina en Chile / In vitro andulafungin susceptibility of 100 of Candida strains obtained previously to the introduction of this echinocandin in Chile

Fungi, particularly yeasts, have become important opportunistic pathogens that can be resistant to antifungal agents or develop resistance. To address this problem, new molecules such as echinocandins, have been developed. Susceptibility to anidulafungin was studied in yeasts isolated previous to the introduction of this drug in Chile. One hundred strains of different yeast species isolated from invasive fungal infections during 2007 and 2008 were studied. Susceptibility testing of anidulafungin was performed by broth microdilution according to CLSI. All strains were susceptible to anidulafungin. MIC50 and MIC90 were 0.125 µg/mL and 1 µg/mL, respectively. Compared to other yeasts, C. parapsilosis showed a slight increase in the MICs for anidulafungin (MIC50, 1 µg/mL, MIC90, 2 µg/mL), but remained within the susceptible range. Both, fluconazole resistant (8) and dose dependant susceptible strains (16) were susceptible to anidulafungin. In vitro, this echinocandin appears to be an effective therapeutic alternative.

Los hongos, especialmente las levaduras, se han transformado en importantes patógenos oportunistas y algunos de ellos tienen o desarrollan resistencia a los antifúngicos. Para enfrentar esta problemática se han desarrollado nuevas moléculas, como las equinocandinas. Este trabajo evaluó la susceptibilidad in vitro a anidula-fungina en levaduras obtenidas previo a la incorporación de este antifúngico en Chile. Para ello, se seleccionaron 100 cepas de diversas especies aisladas de enfermedad fúngica invasora durante los años 2007 y 2008 en Chile, a las cuales se les midió la susceptibilidad in vitro por micro-dilución en caldo para anidulafungina según CLSI. Todas las cepas fueron sensibles a anidulafungina con CIM50 y CIM90 de 0,125 µg/mL y 1 µg/mL, respectivamente. Se detectó un ligero aumento de las CIM en C. parapsilosis respecto a las otras levaduras (CIM50 de 1 µg/mL y CIM90 de 2 µg/mL) considerándose estos valores en el rango de sensibilidad. La correlación de la susceptibilidad frente a fluconazol evidenció que cepas resistentes (n: 8) y sensibles dosis dependientes (n: 16) fueron sensibles a anidulafungina. Esta equinocandina aparece, in vitro, como una alternativa terapeutica efectiva frente a las levaduras aisladas en nuestros pacientes.