Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Infección invasora por Trichosporon asahii en un niño con leucemia linfoblástica aguda

La enfermedad fúngica invasora (EFI) es una de las principales causas de morbimortalidad en los pacientes pediátricos inmunocom- prometidos. Los hongos que con mayor frecuencia causan EFI en este grupo de pacientes corresponden a especies de Candida y Aspergillus. Sin embargo, en los últimos años se ha descrito un aumento de patógenos no clásicos, tales como Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, entre otros. Se presenta un caso de EFI por Trichosporon asahii en un preescolar con una leucemia linfo- blástica aguda en quimioterapia de inducción. Además, se presenta una revisión actualizada de la literatura especializada, con énfasis en la importancia del diagnóstico precoz y el tratamiento antifúngico específico.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and death among immunosuppressed pediatric patients. The fungi that most frequently cause IFD in this group of patients correspond to Candida and Aspergillus species, however, in recent years an increase in non-classical pathogens, such as Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, among others. A case of invasive fungal disease caused by Trichosporon asahii is presented in a preschool patient with acute lymphoblastic leukemia in induction stage. This review highlights the importance of active search for pathogens in immunosuppressed patients, and proposes a specific treatment.

Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infec-tion in patients with malignant hematological disorders / 中国药房

OBJECTIVE To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder. METHODS In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded. RESULTS The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （P＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incidence of adverse events （P＞ 0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （P＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （P＞0.05）. CONCLUSIONS Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

Efficacy analysis of subcutaneous injection of granulocyte-macrophage colony-stimulating factor for prevention of invasive fungal disease in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Comparison of different timing of empirical antifungal strategy in febrile neutropenic children with acute leukemia / 中国小儿急救医学

Objective:To compare the clinical value of early and deferred empirical antifungal strategies in febrile neutropenic children with acute leukemia.Methods:A total of 101 cases of febrile neutropenic children with acute leukemia hospitalized in Qilu Hospital of Shandong University from January 2019 to June 2021 were divided into two groups according to different empirical antifungal strategies.There were 41 cases in early group in which antifungal therapy was given within 4 days of fever, and 60 cases in deferred group in which antifungal therapy was not given within 4 days of fever.Outcomes such as time to stable defervescence, positive diagnosis rate of invasive fungal disease, incidence of severe pneumonia, rate of transference to PICU, exposure time and costs of antifungal agents, and infection-related hospitalization days were compared between two groups.Results:There were no significant differences in time to stable defervescence[5 (4, 7) days vs.5 (3, 7) days, P=0.986], positive diagnosis rate of invasive fungal disease[9.8%(4/41) vs.8.3%(5/60), P=1.000], incidence of severe pneumonia[19.5%(8/41) vs.10.0%(6/60), P=0.174], and rate of transference to PICU[2.4%(1/41)vs.0(0/60), P=0.406] between two groups.Exposure time of antifungal agents was longer in early group than that in deferred group[10 (6, 12)days vs.0 (0, 6)days, P<0.001]. Costs of antifungal agents were higher in early group than those in deferred group[0.78(0.51, 0.95)ten thousand yuan vs.0(0, 0.44)ten thousand yuan, P<0.001]. Infection-related hospitalization days were longer in early group than those in deferred group[16 (10, 21) days vs.9(6, 13)days, P<0.001]. Conclusion:For febrile neutropenic children with acute leukemia, clinical effect of early empirical antifungal strategy is not superior to that of deferred empirical antifungal strategy.Pediatricians should make reasonable antifungal decisions according to overall situation of patients.

Evaluation of a stewardship program of antifungal use at a Brazilian tertiary care hospital

Abstract Introduction Stewardship programs have been developed to optimize the use of antibiotics, but programs focusing on antifungal agents are less frequent. Objective To evaluate the quality of antifungal prescriptions in a tertiary care hospital, and to test if a simple educational activity could improve the quality of prescriptions. Methods The study comprised three phases: 1) Retrospective audit of all antifungal prescriptions in a 6-month period, applying a score based on six parameters: indication, drug, dosage, route of administration, microbiologic adequacy after results of cultures, switching to an oral agent, and duration of treatment; 2) Creation of text boxes in the electronic medical records with information about antifungal agents, shown during prescription; 3) Retrospective audit of all antifungal prescriptions in a 6-month period, applying the same 6-parameters score, and comparison between the two periods. Results Among 333 prescriptions, fluconazole was the most frequently (80.5%) prescribed agent. Hematology (26.7%), Infectious Diseases Department (22.8%), Internal Medicine (15.9%) and Intensive Care Unit (14.4%) were the units with most antifungal prescriptions. The median score for the 333 prescriptions was 8.0 (range 0 - 10), and 72.7% of prescriptions were considered inappropriate. The median and mean scores in the first and second audit were 8.0 and 6.9, and 8.0 and 7.9, respectively (p<0.001). All items that comprised the score improved from the first to the second audit. Likewise, there was a reduction of inappropriate prescriptions (80.2% in the first audit vs. 64.6% in the second audit, p=0.001). Conclusions A large proportion of inappropriate prescriptions was observed, which improved with the implementation of simple educational activities.

Infección rino-sinusal por Exserohilum rostratum en un niño con leucemia mieloide aguda / Sinus infection caused by Exserohilum rostratum in a pediatric patient with acute myeloid leukemia

Resumen Los episodios de neutropenia febril son cuadros graves, que requieren un estudio etiológico exhaustivo y un inicio rápido de antimicrobianos. Dentro de los posibles microorganismos causales se encuentran los de origen fúngico, los que, dependiendo de su grado de invasión tisular, pueden llegar a presentar una alta mortalidad. Presentamos el caso de un niño con una leucemia mieloide aguda, que tras su quimioterapia de inducción, presentó un episodio de neutropenia febril, con una infección rino-sinusal por Exserohilum rostratum, hongo filamentoso que raramente se asocia a cuadros patológicos. Se inició rápidamente terapia antifúngica, lo cual, asociado a un aseo quirúrgico precoz, lograron una respuesta clínica favorable, sin complicaciones. Luego del seguimiento, y tras recibir profilaxis secundaria durante los episodios de neutropenia, no ha vuelto a presentar nuevas lesiones ni compromiso rino-sinusal.

Abstract The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.

Invasive fungal disease in humans: are we aware of the real impact?

Despite the medical advances and interventions to improve the quality of life of those in intensive care, people with cancer or severely immunocompromised or other susceptible hosts, invasive fungal diseases (IFD) remain severe and underappreciated causes of illness and death worldwide. Therefore, IFD continue to be a public health threat and a major hindrance to the success of otherwise life-saving treatments and procedures. Globally, hundreds of thousands of people are affected every year with Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Pneumocystis jirovecii, endemic dimorphic fungi and Mucormycetes, the most common fungal species causing invasive diseases in humans. These infections result in morbidity and mortality rates that are unacceptable and represent a considerable socioeconomic burden. Raising the general awareness of the significance and impact of IFD in human health, in both the hospital and the community, is hence critical to understand the scale of the problem and to raise interest to help fighting these devastating diseases.

Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia / 中华内科杂志

Objective@#To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML).@*Methods@#A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared.@*Results@#During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05].@*Conclusions@#Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

Epidemiología de la enfermedad fúngica invasora por hongos filamentosos en el período 2005 a 2015, en un hospital universitario en Santiago, Chile / Epidemiology of invasive fungal disease by filamentous fungi in the period 2005 to 2015, in a university hospital in Santiago, Chile

Resumen Introducción: La enfermedad fúngica invasora (EFI) por hongos filamentosos es cada vez más frecuente. Objetivo: Estudiar la epidemiología de la EFI en adultos hospitalizados en nuestro centro. Metodología: Estudio retrospectivo de pacientes adultos de un hospital universitario en Santiago, Chile, con EFI por hongos filamentosos entre enero de 2005 y diciembre de 2015. Resultados: Se identificaron 125 episodios, siendo 48% categoria probada, 40% probable y 11% posible según criterios EORTC/MSG, incidencia global 0,47 x 1.000 egresos, 57% pacientes masculinos y edad de 50 ± 16 años. El 66,4% tenía patología hematológica, 11,2% trasplante de órgano sólido, 11,2% enfermedad reumatológica, 11,2% otra condición. Los factores de riesgo fueron neutropenia 44%, corticoterapia 21%, inmunosupresores 13%. Los hongos más frecuentemente identificados fueron Aspergillus spp (53,6%), Mucorales (16%), Fusarium spp (8,8%), Alternaria spp (5,6%), otros filamentosos (3,2%). Todos recibieron antifúngicos, 82% monoterapia, 18% terapia combinada, hubo defocación quirúrgica en 90% de mucormicosis. La mortalidad global fue 42%. Al comparar 2005-2009 vs 2010-2015, hubo un aumento significativo de la incidencia y una tendencia a menor mortalidad en el segundo período. Conclusiones: Durante un período de 10 años, observamos un aumento de la incidencia de EFI por filamentosos, aspergilosis fue la etiología más frecuente y la mortalidad global fue 42%.

Background: Invasive fungal disease (IFD) due to filamentous fungi is increasingly common. Aim: To study the epidemiology of EFI in hospitalized adults in our center. Methods: Retrospective study of adult patients of a university hospital in Santiago, Chile, with EFI due to filamentous fungi between January 2005 and December 2015. Results: 125 episodes were identified, being 48% proven, 40% probable and 11% possible according to EORTC/MSG criteria, overall incidence was 0.47/1,000 admissions, 57% male patients and age 50 ± 16 years. 66.4% had hematological pathology, 11.2% solid organ transplant, 11.2% rheumatology diseases, 11.2% other conditions. The risk factors were neutropenia 44%, corticosteroid therapy 21%, immunosuppressants 13%. The most frequent mould identified were Aspergillus spp (53.6%), Mucorales (16%), Fusarium spp (8.8%), Alternaria spp (5.6%) and other filamentous (3.2%). All received antifungals, 82% monotherapy, 18% combined therapy, there was surgical defocation in 90% of mucormycosis. The overall mortality was 42%. When comparing 2005-2009 vs 2010-2015, there was a significant increase in incidence and a tendency to lower mortality in the second period. Conclusions: Over a period of 10 years, we observed an increase in the incidence of EFI by filamentous, aspergillosis was the most frequent etiology and the overall mortality was 42%.

Prescripción inapropiada de antifúngicos y la necesidad de programas para su uso racional / Inappropriate antifungal prescription and the need for antifungal stewardship programs

Resumen La enfermedad fúngica invasora (EFI) es una entidad que afecta pacientes inmunocomprometidos y críticamente enfermos. En los últimos años, el número de pacientes con riesgo de presentarla viene en aumento, con el consecuente incremento de la formulación de antifúngicos de manera profiláctica, anticipada o empírica. Algunos estudios que evaluaron el uso adecuado de antifúngicos han mostrado que hasta 72% de las formulaciones pueden ser inapropiadas, exponiendo a los pacientes al riesgo de efectos adversos e interacciones medicamentosas, con mayores costos de la atención. Se han recomendado diferentes intervenciones para el control y el uso racional de antimicrobianos, conocidas como "antimicrobial stewardship", las que se pueden aplicar al uso de antifúngicos denominándose "antifungal stewardship"". Se presenta una revisión de la literatura médica sobre el uso apropiado de antifúngicos y el impacto de la implementación de programas de optimización del uso de estos medicamentos en algunos centros.

Invasive fungal disease (IFD) is a condition affecting immunosuppressed and critically ill patients. Recently there has been an increase in the amount of patients at risk for IFD, which implies an increase in the prescription of antifungal agents as prophylactic, pre-emptive or empiric therapy. Some studies evaluating appropriateness of antifungal prescription have shown that inappropriate formulations reach 72%, exposing patients to side effects, pharmacological interactions and rising costs. Some groups have recommended many interventions to control and make a rational use of antimicrobials, into strategies known as "antimicrobial stewardship", these interventions are useful also for antifungal agents and it has been named "antifungal stewardship". Here we present a narrative review of the scientific literature showing published articles about appropriate use of antifungal agents and the experience of some centers after implementing antifungal stewardship programs.

Progress for diagnosis of invasive fungal disease in children / 国际儿科学杂志

Invasive fungal disease (IFD) is common in immunocompromised children,particularly in those with hematological malignancies.IFD is associated with onset complications and can cause high morbidity and mortality.In recent years,the incidence of IFD is increasing.More cases are reported in non-neutropenic and immunocompetent children without apparent underlying conditions.Early diagnosis and prompt therapy is key to better prognosis.This review focuses on the diagnostic methods on IFD.

Clinical evaluation of posaconazole for preventing invasive fungal disease in the aplastic anemia patients receiving transplantation / 中国感染与化疗杂志

Objective To evaluate the efficacy and safety of posaconazole for preventing invasive fungal disease (IFD) in the aplastic anemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Methods A total of 46 aplastic anemia patients received allogeneic HSCT. They were treated with oral posaconazole 200 mg, three times a day from HSCT pretreatment to granulocyte recovery after transplantation. G test and GM test were done 1, 2 and 4 weeks after the end of posaconazole treatment, and chest CT scan repeated 4 weeks after the end of posaconazole treatment. Posaconazole prophylaxis was defined as successful if there were no clinical manifestations indicative of fungal infection. Results All the 46 patients experienced neutropenia. The median of absolute neutrophil count (ANC) nadir was 0.02 (0-0.05)×109/L for a median time of 10 (8-19) days. The median duration of posaconazole prophylaxis was 26 (15-41) days. Neutropenic fever was reported in 45 patients, which lasted a median time of 5 (1-13) days. Six patients (13.3％ of the patients with neutropenic fever) failed to respond to the empirical treatment of broad spectrum antibiotics with persistent fever over 7 days. Their treatment was switched to short-term empirical treatment with broad spectrum antifungal agents. However, subsequent G test, GM test and chest CT showed negative results. None of the six patient was consistent with IFD diagnosis. Breakthrough fungal infection was not considered. Oral posaconazole solution was resumed for preventing IFD. G test, GM test and chest CT scan did not show any sign of fungal infection 1, 2 and 4 weeks after the end of posaconazole prophylactic treatment in all the 46 patients, proving the success of oral posaconazole in preventing IFD. Posaconazole was not discontinued due to adverse drug reaction in any patient. Conclusions Posaconazole is effective for preventing IFD in the aplastic anemia patients receiving HSCT with good safety profile and few adverse reactions.

Evaluación del rendimiento de 1, 3-β -d-glucano como apoyo diagnóstico de infecciones invasoras por Candida spp. en pacientes críticos adultos / The 1,3-β -d-glucan in critical adult patients as diagnostic tool for invasive Candida spp. infection, performance evaluation

Resumen Introducción: La enfermedad fúngica invasora (EFI) se reconoce como causa importante de morbi-mortalidad en pacientes críticos. La mayoría de estas infecciones son provocadas por Candida spp. para cuyo diagnóstico existen importantes limitaciones. Objetivo: Realizar una evaluación inicial de la utilidad de la medición del 1,3-β-D- glucano (BDG) como herramienta diagnóstica de apoyo de las infecciones invasoras por Candida spp. en pacientes críticos. Pacientes y Método: Estudio prospectivo de pacientes mayores de 18 años hospitalizados en unidades de pacientes críticos por más de cinco días, con fiebre sin foco claro y dos o más factores de riesgo para EFI por Candida spp. Se obtuvieron muestras para BDG en dos días consecutivos. Los resultados se confrontaron con el diagnóstico definitivo de candidemia/candidiasis invasora (C/CI) demostrado según cultivos. Resultados: El valor promedio de BDG en los pacientes con diagnóstico de C/CI fue 224,3 ± 213,7 pg/ml y en aquellos sin C/CI 63,8 ± 76,7 pg/ml (p: 0,02). La sensibilidad y especificidad de BDG para diagnóstico de C/CI fue 60 y 92%, respectivamente. El valor predictor positivo fue 60% y el valor predictor negativo de 92%. Conclusión: BDG puede considerarse como un examen de apoyo en el diagnóstico de C/CI en pacientes críticos con factores de riesgo.

Background: Invasive fungal infections are important causes of morbimortality in critical patients. Most of these infections are caused by Candida spp. which diagnosis has important limitations. Aim: Initial evaluation of the utility of 1,3-β-D-glucan (BDG) as a diagnostic tool for invasive candida infections in critical patients. Patients and Methods: Adult patients over 18 years old, hospitalized in intensive care units for more than five days, with fever > 38 °C of unclear origin and two or more risk factors for invasive Candida spp. infection were included. Samples for BDG were obtained on two consecutive days. The results were compared with definitive diagnosis of candidemia/invasive candidiasis (C/IC) confirmed by cultures. Results: Median value of BDG in patients with C/IC was 224.3 ± 213.7 pg/ml and in patients without C/IC was 63.8 ± 76.7 pg/ml (p: 0.02). Sensitivity and specificity for the diagnosis of C/IC were 60 and 92%, respectively. Positive predictive value was 60% and negative predictive value was 92%. Conclusion: BDG could be considered as a complementary diagnostic tool for the diagnosis of C/IC in critical patients with risk factors.

Effect of Pharmaceutical Consultation on Invasive Fungal Disease in Patients with Hematologic Malignancies / 中国药学杂志

OBJECTIVE: To explore how to carry out pharmaceutical consultation for anti-infection treatment in neutropenic hematological patients with invasive fugal disease and elaborate the value of clinical pharmacists in anti-infection treatment. METHODS: A total of 41 hematologic malignancies patients with invasive fungal disease who were consulted by clinical pharmacist from October 2014 to June 2016 were enrolled into the study. The etiology, bacteria complication, and infection site were summarized. The other 41 agranulocytosis patients complicated with invasive fungal disease without clinical pharmacist consultation randomly sampled by HIS were used as the control. Statistical analysis were carried out to evaluate the effect of anti-infection treatment. The authors also discussed that as a clinical pharmacist how to carry out pharmaceutical consultation through several typical anti-fungal infection cases. RESULTS: Totally 45 strains of fungi were isolated from the secretion specimens obtained from the 41 patients, including Candida albicans, Candida glabrata, Candidakrusei, Candida tropicalis, Aspergillums, and Cryptococcosis, among which Candida albicans accounted for 60.0%, followed by Aspetgillus (13.3%), Candidakrusei (11.1%), Candida glabrata (6.67%), Candida tropicalisi (6.67%), and Cryptococcosis (2.2%). The main infection site was the lung, followed by the digestive tract and blood stream. The positive rate of bacteria culture was 58.5% among the 41 patients, and the major isolated bacteria were Escherichia colis, Pseudomonas aeruginosa, Enterococcus, and Pseudomonas maltophilia. For the antifungal treatment involving the clinical pharmacists, the cure rate was 48.8%, the significant effective rate was 34.2%, the improved effective rate was 7.4%, the total effective rate of treatment was 72.9%, and the failure rate was 9.3%. There was significant difference in the curative effect between the clinical pharmacist consultation group and the control group (P<0.05). CONCLUSION: The incidence of fungal infection in agranulocytosis patients is high, and most of the patients are complicated with bacteria infection. The most frequently infected site is respiratory tract. Clinical pharmacists can play an important role in the treatment of invasive fungal disease in agranulocytosis patients to ensure the treatment safety and efficacy.

Invasive fungal diseases in children with hematologic malignancies / 国际儿科学杂志

Invasive fungal diseases (IFD) are important causes ot morbidity and mortality in children with hematological malignancies.Although Candida remains the most common fungal pathogen in oncology pa tients,the epidemiology has recently shifted toward non-albicans species.However,Aspergillus has also seen a recent rise.Early recognition and prompt antifungal treatment are key to the control of IFD.We provide clinicians with evidence-based recommendations on strategies for disease diagnosis and management in this review.

Efficacy of posaconazole in preventing invasive fungal disease in hematologic patients with neutropenia / 中国感染控制杂志

Objective To evaluate the prophylactic efficacy and safety of posaconazole against invasive fungal disease(IFD)in hematologic patients with neutropenia.Methods Medical records of 18 hematologic patients with neutropenia received posaconazole for preventing IFD in a Beijing hospital between 2014 and 2015,the efficacy and safety was evaluated.Results There was no clinical diagnosis or confirmed diagnosis of IFD among 18 patients during posaconazole prophylaxis period,none of patients stopped posaconazole due to severe adverse reaction.Two patients with acute myeloid leukemia(AML) died of pulmonary infection,1 of whom isolated Stenotrophomonas maltophilia from sputum culture on the 12th day of posaconazole prophylaxis,the other isolated Escherichia coli from sputum culture on the 14th day of posaconazole prophylaxis.Other patients all adherence to posaconazole prophylaxis until granulocyte count recovered,patients were followed up until 100 days medication,no death occurred.The lowest peripheral neutrophil count was(0.00-0.27) x 109/L during posaconazole prophylaxis period,with the median of 0.02 x 109/L;the duration of posaconazole prophylaxis was 8-27days,with the median of 16 days;among patients without IFD breakthrough or received systemic use of other antifungal agents,there were 2 (11.1％) all-cause death within 100 days;there were no adverse reaction,such as liver function abnormalities≥grade 2 and kidney function abnormalities≥grade 2,as well as QTc prolongation.Conclusion Posaconazole is effective for preventing IFD in hematologic patients with neutropenia,adverse reaction is rare.

Laboratory examination of invasive fungal disease in children and its evaluation / 中国小儿急救医学

Pediatric invasive fungal disease( IFD)often lacks characteristic clinical manifestations and imaging changes. It is a severe disease in ICU and is unlikely to be diagnosed early. The diagnosis of IFD is typically based on laboratory tests targeting at the population at risk. The laboratory tests for IFD generally include direct tests( smear microscopy,fungal culture,histopathologic examination,etc. ),serologic tests( tests for 1,3-β-D dextran and galactomannan,etc. ),and certain progresses have been made in molecular biologi-cal tests in recent years. It is key to diagnosis of IFD to use laboratory tests rationally and accurately interpret the laboratory results.

Development of risk evaluation models for critically ill patients at high risk of invasive fungal disease / 国际儿科学杂志

Invasive fungal disease(IFD) is one of the causes leading to death in intensive care unit,and now more likely to occur in non-neutropenic critically ill patients.Early diagnosis and appropriate selection of patients at high risk of IFD to receive prophylactic antifungal therapy are of great concern.Risk factors related to IFD were established by multivariable analysis and then risk evaluation models were developed.Candida score could accurately select patients who would benefit from early antifungal treatment.Evaluation and validation of risk models for non-neutropenic critically ill patients at high risk of IFD were reviewed in this article.

Enfermedad fúngica invasora (EFI) por hongos filamentosos en la Región de Valparaíso, Chile, desde la implementación del diagnóstico rápido de laboratorio / Invasive fungal disease (IFD) by filamentous fungi in the Valparaíso Region, Chile, since implementation of rapid laboratory diagnosis

Introduction: Invasive fungal diseases (IFD) by filamentous fungi are a common cause of morbidity and mortality in immunocompromised patients, especially those with myeloid leukemia. In 2011 a protocol for the rapid diagnosis of IFD by filamentous fungi was implemented in Valparaiso Region. Objectives: To describe cases of IFD by filamentous fungi of the Valparaíso Region, since the implementation of rapid diagnosis and to compare results with the period 2004-2009. Materials and Method: Descriptive and prospective study conducted in two public hospitals: Carlos van Buren at Valparaiso and Gustavo Fricke at Viña del Mar. We selected patients with a diagnosis of filamentous fungal diseases considering the EORTC/MSG criteria. Demographics, underlying diseases, risk factors for EFI, galactomannan (GM) results in blood and bronchoalveolar lavage, cultures and biopsies, treatment and overall lethality rates at 30 days were registered. Results: Eighteen patients were detected, 6 with proven and 12 probable IFD. Nine were diagnosed by GM, 8 by culture and two with both methods. In cases which the agent (9/18) was isolated from Rhizopus oryzae was the most frequent. When comparing overall lethality with the period 2004-2009, there was a reduction of 47.8%, which was statistically significant. Conclusions: Compared to data previously published in the region, demographic and comorbidities of patients with IFD caused by filamentous fungi are similar, however the currently rapid diagnosis protocol has improved survival of patients and lethality experienced overall decrease.

Introducción: la enfermedad fúngica invasora (EFI) por hongos filamentosos es una causa frecuente de morbilidad y mortalidad en pacientes inmunocomprometidos, en especial en aquellos con leucemia mieloide. En el 2011 se implementó en la Región de Valparaíso un protocolo de diagnóstico rápido de la EFI por hongos filamentosos. Objetivos: describir los casos de EFI por hongos filamentosos de la Región de Valparaíso, desde la implementación del diagnóstico rápido y compararlos con el período 2004-2009. Materiales y Método: Estudio descriptivo y prospectivo realizado en los hospitales públicos Carlos van Buren de Valparaíso y Gustavo Fricke de Viña del Mar. Se seleccionaron aquellos pacientes con diagnóstico de EFI por hongos filamentosos considerando los criterios EORTC/MSG. Se obtuvieron datos demográficos, enfermedad de base, factores de riesgo para EFI, resultados de galactomanano (GM), cultivos y biopsias, tratamiento y letalidad global a 30 días. Resultados: Se identificaron 18 pacientes, seis con EFI probadas y 12 probables. Nueve fueron diagnosticados con galactomanano, ocho con cultivos y uno con los dos métodos. En los casos en que se aisló el agente (9/18), Rhizopus oryzae fue el más frecuente. Al comparar la letalidad global con la del período 2004-2009, hubo una reducción de 47,8%, la cual fue estadísticamente significativa. Conclusiones: En relación a lo publicado anteriormente en la región, se conservan las características demográficas y de co-morbilidad de los pacientes con EFI por hongos filamentosos; sin embargo, la introducción del nuevo protocolo de diagnóstico rápido se asoció a una disminución en la letalidad global.