The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). RESULTS: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12-0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14-0.69; p=0.004; I2=0%). CONCLUSIONS: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.

The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis / Eficacia de fluconazol para profilaxis antifúngica en los pacientes de diálisis peritoneal: revisión sistemática y metaanálisis

Introduction and objectives: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. Materials and methods: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). Results: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12–0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14–0.69; p=0.004; I2=0%). Conclusions: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.(AU)

Introducción y objetivos: La eficacia de fluconazol como estrategia profiláctica en los pacientes con enfermedad renal crónica (ERC) sometidos a diálisis peritoneal (DP) con exposición antibiótica previa es controvertida en la literatura actual. El objetivo de este estudio fue comparar la estrategia de profilaxis con fluconazol frente a no profilaxis para los pacientes de DP con régimen antibiótico por episodios previos de peritonitis. Materiales y métodos: Realizamos una revisión sistemática y metaanálisis de estudios observacionales y ensayos controlados aleatorizados (ECA), comparando la profilaxis con fluconazol y la no profilaxis para la peritonitis relacionada con DP. Dicha búsqueda se realizó en PubMed, EMBASE y Cochrane Central el 23 de enero de 2023. El resultado de interés fue la aparición de peritonitis fúngica (PF). Resultados: Incluimos seis estudios (1 ECA, 5 observacionales) con 4.515 episodios de peritonitis, de los cuales 1.098 (24,8%) recibieron profilaxis de fluconazol en dosis variables, mientras que 3.417 (75,6%) no recibieron profilaxis durante los episodios de peritonitis. En general, la profilaxis de fluconazol estuvo asociada a una menor incidencia de PF (OR: 0,22; IC 95%: 0,12-0,41; p<0,001; I2=0%). El análisis de subgrupo de los estudios que administraron dosis diarias de fluconazol también demostró una incidencia reducida de PF en los pacientes que recibieron profilaxis antifúngica (OR: 0,31; IC 95%: 0,14-0,69; p=0,004, I2=0%). Conclusiones: En este metaanálisis de 4.515 episodios de peritonitis relacionada con DP, la profilaxis con fluconazol redujo significativamente los episodios de PF, en comparación con la no profilaxis antifúngica.(AU)

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Profilaxis antifúngica primaria en pacientes oncohematológicos: ¿a quiénes, cuándo y con qué? / Primary antifungal prophylaxis in oncohematological patients: who, when, and with what?

Resumen Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hos pitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.

Abstract Invasive fungal infections (IFI) are among the main infectious complications in patients with hema tological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with cortico steroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recom mendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.

[Invasive aspergillosis in the patient with oncohematologic disease]. / Aspergilosis invasora en el paciente con enfermedad oncohematológica.

Invasive aspergillosis is the most common invasive fungal infection in patients with acute hematological malignancies or treated with hematopoietic stem cell transplantation due to the marked alteration of the physiological mechanisms of antifungal immunity that takes place in these situations. For this reason, antifungal prophylaxis has a relevant role in these patients. The introduction of new antifungal agents has motivated the updating of recommendations for prophylaxis and treatment in different guidelines. The objectives of this chapter are a brief review of the mechanisms of immunity against fungi, the definition of risk for developing an invasive fungal infection and an update of the prophylaxis recommendations and treatment of invasive aspergillosis in the group of patients with hematological diseases.

Complicaciones infecciosas en pacientes con leucemia mieloide aguda / Infectious complications in acute myeloid leukemia patients

La leucemia aguda ha sido reconocida como una enfermedad compleja y rápidamente fatal desde su primera descripción hace 150 años. Librada a su historia natural, la leucemia mieloide aguda lleva a la muerte en pocos meses. Las infecciones son la principal causa de muerte, siendo la bacteriemia y la neumonía las más frecuentes.Los avances ocurridos en los últimos 50 años, como el advenimiento de quimioterapias efectivas, la mejor comprensión de la patogénesis de las complicaciones infecciosas en el paciente neutropénico, la disponibilidad de agentes anti infecciosos de amplio espectro y la mejoría en los cuidados de soporte contribuyeron a mejorar esta situación. En relación a otras enfermedades oncohematológicas, la leucemia mieloide aguda registra la mayor incidencia de eventos febriles, siendo el período de mayor riesgo el de la inducción a la remisión.La fiebre de origen desconocido, la multirresistencia bacteriana y las infecciones fúngicas invasivas constituyen un desafío para el equipo de trabajo.El uso de profilaxis antibacteriana y antifúngica no reemplaza a las medidas de prevención de carácter institucional

Acute leukemias have been recognized as complex and radiply fatal diseases since its first description 150 years ago. Delivered to its natural history, acute myeloid leukemia leads to death in a few months. Infections are the main cause of death, being bacteremia and pneumonia the most frequent. Advances in the last 50 years, such as the advent of effective chemotherapy, a best understanding of the pathogenesis of infectious complications in the neutropenic patient, the availability of broad-spectrum anti-infective agents and better supportive care helped improve this situation. Among other oncological diseases, acute myeloid leukemia has the highest incidence of febrile events, being induction to remission the period of greatest risk. Fever of unknown origin, bacterial multidrug resistance and invasive fungal infections are a challenge for the medical team. The use of antibacterial and antifungal prophylaxis does not replace institutional preventive measures

Galactomannan enzyme immunoassay and quantitative Real Time PCR as tools to evaluate the exposure and response in a rat model of aspergillosis after posaconazole prophylaxis.

INTRODUCTION: A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole. METHODS: Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used. RESULTS: Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain. CONCLUSION: This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis.