RESUMO
Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0%(95%CI:64.1%~75.9%)and 20.0%(95%CI:11.9%~32.5%),respectively,while those of the fungal infection patients were 54.5%(95%CI:49.5%~69.5%)and 36.4%(95% CI:15.5%~70.3%),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.
RESUMO
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.
RESUMO
With the increasing number of people with immune deficiency in recent years, fungal infections become an important factor threatening human health.Likewise, the number of children who are immunosuppressed due to hematological diseases, malignancies, use of immunosuppressants and spectrum antibacterial drugs has increased, leading to a high mortality of fungal infections.Moreover, infections of the non-candida albicans and aspergillu are prevalent, serving as important causes for the death of critically ill children. Therefore, this review aims to introduce and summarize the epidemiological characteristics, diagnosis and treatment of pediatric invasive fungal infections, thus yielding the concern of pediatric invasive fungal infections, reducing the occurrence of pediatric fungal infections and improving the prognosis.
RESUMO
Fungal infections gradually attract global public health attention. Candida, Aspergillus, and Cryptococcus are the most common pathogens of fungal infections.With the widespread use of antifungal drugs, fungal resistance is gradually increasing.Clarifying the current status of antifungal drug resistance and the mechanism is helpful for rational treatment of fungal infections.
RESUMO
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.
Assuntos
Humanos , Masculino , Pré-Escolar , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Tricosporonose/complicações , Infecções Fúngicas Invasivas , Trichosporon/isolamento & purificação , Tricosporonose/diagnóstico , Tricosporonose/microbiologia , Tricosporonose/tratamento farmacológico , Antifúngicos/uso terapêuticoRESUMO
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.
RESUMO
This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.
Assuntos
Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anticorpos Biespecíficos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Indução de RemissãoRESUMO
Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.
RESUMO
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.
RESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Humanos , Criança , Ascomicetos/isolamento & purificação , Sinusite/complicações , Sinusite/microbiologia , Sinusite/tratamento farmacológico , Leucemia Mieloide Aguda/complicações , Micoses/complicações , Micoses/tratamento farmacológico , Antifúngicos/uso terapêutico , Resultado do Tratamento , Neutropenia/etiologiaRESUMO
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.
RESUMO
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.
Assuntos
Humanos , Infecções Fúngicas Invasivas/diagnóstico , Fungos/isolamento & purificação , Fungos/classificação , Qualidade de Vida , Hospedeiro Imunocomprometido , Efeitos Psicossociais da Doença , Infecções Fúngicas Invasivas/complicações , Infecções Fúngicas Invasivas/mortalidade , Unidades de Terapia IntensivaRESUMO
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%.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Chile/epidemiologia , Estudos Retrospectivos , Fungos , Antifúngicos/uso terapêuticoRESUMO
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.
Assuntos
Humanos , Prescrição Inadequada/prevenção & controle , Infecções Fúngicas Invasivas/tratamento farmacológico , Gestão de Antimicrobianos/métodos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Hospedeiro Imunocomprometido , Monitoramento de Medicamentos , Prescrição Inadequada/estatística & dados numéricos , Infecções Fúngicas Invasivas/diagnósticoRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , beta-Glucanas/sangue , Candidíase Invasiva/diagnóstico , Biomarcadores/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Candidíase Invasiva/sangueRESUMO
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.