RESUMO
@#Chronic pulmonary aspergillosis (CPA) is a rare disease. It is usually diagnosed in immunocompromised patients with other chronic respiratory disorders. Diagnosis can be challenging due to non-specific symptoms. It is based on clinical, radiological, and microbiological criteria and excludes other causes of the symptoms. The outcomes of antifungal treatment may be unpredictable as optimal treatment duration has not yet been standardized. This is the case of a 74-year-old male who presented via teleconsultation with hemoptysis. GeneXpert for pulmonary tuberculosis was negative. Chest radiograph showed a cavitary lesion with an aspergilloma within. This led to a longstanding treatment effort with voriconazole, as he was a poor candidate for surgical resection due to the risk of post-operative complications. Three months into the treatment, the patient unexpectedly suffered from a severe episode of dyspnea, culminating in cardiac arrest. While the patient has been resuscitated with no residuals, it is only one of the many steps on his road to recovery and his second lease on life, this time coming to terms with his own preferences and values regarding his medical care. The patient showed clinical improvement and the promise of a cure in his fifth month of treatment. Learning points include the role of family physicians in a patient’s well-being even in specialized cases, the value of individualized care and the application of technology in hybrid consultation and monitoring.
Assuntos
Aspergilose , Hemoptise , VoriconazolRESUMO
OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Assuntos
Humanos , Masculino , Feminino , Voriconazol/uso terapêutico , Antifúngicos/uso terapêutico , Proteína C-Reativa , Creatinina , Glucocorticoides , Estudos Retrospectivos , Monitoramento de Medicamentos , Doenças HematológicasRESUMO
Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC50, and MIC90 of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Assuntos
Humanos , Antifúngicos/farmacologia , Fluconazol/farmacologia , Candida tropicalis , Voriconazol/farmacologia , Itraconazol/farmacologia , Estudos Retrospectivos , Candida , China/epidemiologia , Equinocandinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Objective: To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C. tropicalis isolates from 2017 to 2021 in East China. Methods: Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected C. tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired t-test. Results: In total, 305 C. tropicalis isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of C. tropicalis to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC50, and MIC90 of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (t=9.95, P<0.05), posaconazole (t=9.99, P<0.05), and voriconazole (t=10.01, P<0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (t=1.17, P>0.05), both of which were significantly higher than MICA (t=11.56, P<0.05; t=4.15, P<0.05). Conclusion: The clinical isolates of C. tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in C. tropicalis.
Assuntos
Humanos , Antifúngicos/farmacologia , Fluconazol/farmacologia , Candida tropicalis , Voriconazol/farmacologia , Itraconazol/farmacologia , Estudos Retrospectivos , Candida , China/epidemiologia , Equinocandinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.
Assuntos
Tacrolimo/agonistas , Fator de Impacto , Voriconazol/agonistas , Citocromo P-450 CYP2C19/análise , Técnicas In Vitro/métodos , Preparações Farmacêuticas/administração & dosagem , Adaptação Psicológica/classificaçãoRESUMO
Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.
Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.
Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Infecções Fúngicas Invasivas/tratamento farmacológico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus fumigatus , Comorbidade , Fluconazol/uso terapêutico , Criança Hospitalizada , Anfotericina B/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Hospedeiro Imunocomprometido/imunologia , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans , Candidíase Invasiva/diagnóstico , Candidíase Invasiva/tratamento farmacológico , Voriconazol/uso terapêutico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/mortalidade , Caspofungina/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
La fungemia por Geotrichum spp. es poco frecuente y altamente letal. En el Instituto Nacional de Cancerología de Bogotá solo se han reportado dos casos: uno entre el 2001 y el 2007, y el otro entre el 2012 y el 2018. Este tipo de infección es más común en pacientes con algún grado de compromiso del sistema inmunitario, por lo que puede presentarse en pacientes con neoplasias hematológicas malignas. Se presenta el caso de un hombre de 27 años con recaída de leucemia linfoblástica aguda, que ingresó con poliartralgias de cinco días de duración. También cursaba con neutropenia febril, celulitis sin abscesos y bacteriemia por Staphylococcus aureus resistente a la meticilina para lo cual recibió terapia con oxacilina y cefepime. Sin embargo, persistía la neutropenia febril por lo que se sospechó una infección fúngica invasora. Se tomó un nuevo set de hemocultivos y se inició tratamiento antifúngico. En los hemocultivos se identificaron artroconidias y mediante espectrometría de masas por láser de matriz asistida de ionización-desorción se confirmó la presencia de Geotrichum spp. Se ajustó el tratamiento antifúngico con deoxicolato de anfotericina B por 14 días y voriconazol por cuatro semanas. Luego de una estancia prolongada se le dio de alta. Aunque la incidencia de la fungemia por Geotrichum spp. es baja, en pacientes con neoplasias hematológicas malignas debe considerarse en el contexto de una neutropenia febril que es persistente a pesar del tratamiento antimicrobiano de amplio espectro. La identificación de los agentes causantes de fungemias con herramientas de proteómica, como la espectrometría de masas mencionada, permite ajustar el tratamiento dirigido y reducir las complicaciones, la estancia hospitalaria y la mortalidad.
Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, non- abscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Geotricose , Anfotericina B , Fungemia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , VoriconazolRESUMO
La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.
The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.
Assuntos
Fusarium , Anfotericina B , Fungemia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , VoriconazolRESUMO
INTRODUCCIÓN. La aspergilosis laríngea en individuos inmunocompetentes, aunque rara, se reporta cada vez con más frecuencia; por lo cual, es necesario comprender mejor los aspectos clínicos y terapéuticos más adecuados para abordar su atención. OBJETIVO. Documentar los aspectos clínicos asociados al diagnóstico y el tratamiento de la aspergilosis laríngea en sujetos inmunocompetentes. METODOLOGÍA. Se realizó un estudio Bibliográfico Narrativo de carácter retrospectivo, donde se evaluaron los casos clínicos reportados de personas inmunocompetentes con aspergilosis laríngea desde el año 1983 hasta el 2022. Se hizo una revisión bibliográfica en las bases de datos PubMed/Medline y ScienceDirect, y se incluyeron todos los casos reportados en sujetos inmunocompetentes. RESULTADOS. Se identificaron 30 casos clínicos que cumplieron con los criterios de inclusión dentro de un grupo de 586 artículos revisados. El patógeno más reportado fue Aspergillus fumigatus y la evaluación histopatológica la principal herramienta para diagnosticar la aspergilosis. Se reportaron más casos en mujeres con un 58%. La mayor incidencia se observó en sujetos entre 20 y 49 años de edad. Los síntomas más comunes fueron disfonía, disnea y tos. El tratamiento farmacológico empleado actualmente es el Itraconazol seguido por el Voriconazol. CONCLUSIONES. La evidencia reportada mostró que la aspergilosis laríngea en pacientes inmunocompetentes podría estar dejando de ser un evento "poco común" por lo que debe prestarse más atención a su diagnóstico y tratamiento.
INTRODUCTION. Laryngeal aspergillosis in immunocompetent individuals, although rare, is reported with increasing frequency; therefore, it is necessary to better understand the most appropriate clinical and therapeutic aspects to address its care. OBJECTIVE. To document the clinical aspects associated with the diagnosis and treatment of laryngeal aspergillosis in immunocompetent subjects. METHODOLOGY. A retrospective Narrative Bibliographic study was performed, where clinical case reports of immunocompetent subjects with laryngeal aspergillosis from 1983 to 2022 were evaluated. A literature review was performed in PubMed/Medline and ScienceDirect databases, and all reported cases in immunocompetent subjects were included. RESULTS. Thirty clinical cases that met the inclusion criteria were identified from a pool of 586 articles reviewed. The most reported pathogen was Aspergillus fumigatus and histopathologic evaluation the main tool for diagnosing aspergillosis. More cases were reported in women with 58%. The highest incidence was observed in subjects between 20 and 49 years of age. The most common symptoms were dysphonia, dyspnea and cough. The pharmacological treatment currently used is Itraconazole followed by Voriconazole. CONCLUSIONS. The evidence reported showed that laryngeal aspergillosis in immunocompetent patients may no longer be a "rare" event and more attention should be paid to its diagnosis and treatment.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Aspergilose/tratamento farmacológico , Aspergillus fumigatus , Terapêutica , Doenças da Laringe , Diagnóstico , Imunocompetência , Aspergillus , Aspergillus niger , Itraconazol , Tosse , Dispneia , Equador , Disfonia , Voriconazol , Laringe/patologiaRESUMO
Resumen Presentamos el caso de un escolar de 10 años, con el diagnóstico de una recaída de una leucemia mieloide aguda que cursó con un episodio de una neutropenia febril de alto riesgo, posterior a un ciclo intensivo de quimioterapia, evolucionando con una infección fúngica invasora demostrada por histopatología. Se inició tratamiento con voriconazol intravenoso, evolucionando con concentraciones plasmáticas erráticas que requirieron sucesivos ajustes de dosis, lo que también ocurrió con la administración oral del medicamento. Finalmente, tuvo una respuesta favorable al tratamiento, a pesar de la dificultad de la dosificación para alcanzar niveles terapéuticos. La búsqueda activa y la terapia antifúngica anticipada, así como la monitorización seriada de concentraciones terapéuticas de voriconazol, permitieron un tratamiento antifúngico óptimo y oportuno, mejorando el pronóstico del paciente.
Abstract We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.
Assuntos
Humanos , Masculino , Criança , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Estudos Retrospectivos , Voriconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
INTRODUCCIÓN: Voriconazol es el antifúngico de elección para el tratamiento de la aspergilosis invasora (AI). Concentraciones plasmáticas (CPs) > 1 μg/mL se han asociado a mejores resultados terapéuticos, las que no siempre se alcanzan durante el tratamiento en niños inmunocomprometidos. Dada la necesidad de iniciar una terapia precoz y efectiva de la infección, es relevante establecer el régimen de administración de voriconazol que se asocie con CPs óptimas en esta población. OBJETIVO: Comparar las CPs y seguridad de voriconazol intravenoso (IV), dosificado BID y TID en niños inmunocomprometidos con indicación de tratamiento antifúngico. MÉTODO: Estudio observacional retrospectivo de enero de 2015 a julio de 2018 en un hospital pediátrico de alta complejidad de Santiago de Chile, en pacientes de 0 a 17 años que recibieron tratamiento con voriconazol IV. Se excluyeron aquellos con terapia de reemplazo renal, falla hepática y/o falla renal. Se compararon las CPs valles entre un grupo con régimen de dosificación BID y otro grupo con administración TID. Se evaluaron las reacciones adversas en ambos grupos. RESULTADOS: Se obtuvieron 137 CPs valles en 76 niños, con una mediana de edad de 9 años (0-17 años) en el grupo BID y 9 años (0-16 años) en el grupo TID, con una mediana de peso de 27 kg (6-83 kg) y 28 kg (9,3-60 kg), respectivamente. Resultados: Pacientes 1 gg/mL en comparación con la administración BID (p = 0,001). Se reportaron ocho reacciones adversas, principalmente fotofobia, sin encontrarse diferencias significativas entre grupo BID y TID. CONCLUSIÓN: Dosificaciones TID están asociadas a una mayor probabilidad de obtener una adecuada exposición a voriconazol en pacientes < 12 años en comparación a dosificaciones BID, con baja frecuencia de reacciones adversas.
BACKGROUND: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) > 1 μg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. AIM: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. METHOD: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. RESULTS: 137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients 1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. CONCLUSION: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients < 12 years old compared to BID dosages, with a low frequency of adverse reactions.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas , Preparações Farmacêuticas , Estudos Retrospectivos , Voriconazol , AntifúngicosRESUMO
Background: Pulmonary aspergillosis (PA) is common among patients with tuberculosis (TB). With both infections presenting with similar clinical and radiologic features, diagnosis of PA is often made too late or missed completely due to lack of clinical suspicion and poor diagnostic laboratory capacity for mycotic infections prevalent in our settings. We present a case of preventable mortality caused by delayed diagnosis and treatment of PA in a patient with pulmonary TB (PTB). Case presentation: A 13-year-old female was diagnosed and treated for PTB, having received anti-TB regimen for 8 months in a mission hospital from where she was referred due to worsening cough, chest pain and progressive breathlessness. The patient was re-assessed and investigated, with GeneXpert detecting Mycobacterium tuberculosis, susceptible to rifampicin. Diagnosis of pulmonary tuberculosis complicated by right pneumothorax was made indicating an emergency thoracotomy and chest tube insertion and continuation of the first line anti-TB regimen. At about 2 weeks into admission, patients had features of superimposed acute bacterial sepsis with fever becoming high grade, marked neutrophilia with toxic granulation and elevated sepsis biomarker, and this necessitated empiric antibiotic treatment with parenteral meropenem and vancomycin. However, the patient only had mild clinical improvement following which there was progressively worsening respiratory symptoms and massive haemoptysis. Result of sputum fungal study was available on admission day 20 and revealed a growth of Aspergillus flavus. Treatment with intravenous voriconazole was however commenced rather late when the fungal respiratory disease could no longer be remedied. The patient died on admission day 23. Conclusion: Diagnosis of PA in patients with background TB is often made too late to guarantee timely and effective antifungal treatment with negative consequences on patients' outcomes. Improving clinical and laboratory capacities is essential to reducing mortality from PA in healthcare facilities.
Assuntos
Humanos , Tuberculose , Diagnóstico , Aspergilose Pulmonar , Mycobacterium tuberculosis , VoriconazolRESUMO
La creciente emergencia de las enfermedades infecciosas y el aumento del número de individuos que tienen afectada su competencia inmunológica se ha convertido en un reto. Por otro lado, considerando el género Aspergillus, como un agente etiológico de infección, causa importante de morbilidad y mortalidad en pacientes inmunocomprometidos. Presentamos el caso de preescolar femenino de 3 años y 8meses con antecedente de teratoma maduro fetiforme, quien posterior a 6 meses de su exéresis, se realiza tomografía axial computarizada (TAC) de Tórax control evidenciándose bronquiectasias centrales con opacidades tubulares y saculares de distribución bronquial, con localización principalmente en lóbulo superior de hemitórax izquierdo, disminución del volumen pulmonar ipsilateral con incipiente desplazamiento del cardiomediastino a la izquierda y escaso derrame pleural izquierdo, examen físico sin alteraciones, por lo que ingresa con diagnóstico de enfermedad granulomatosa en estudio. Se realiza detección de antígeno galactomanano que reporta positivo en dos determinaciones por lo que se replantea el diagnóstico a Aspergilosis Pulmonar Invasiva, cumple tratamiento con voriconazol por 21 días, con mejoría significativa de las lesiones pulmonares en TAC de tórax, egresando con tratamiento con itraconazol a cumplir por 6 semanas. El inicio precoz del tratamiento constituye un factor pronóstico fundamental de la aspergilosis invasiva, siendo el voriconazol la primera línea(AU)
The growing emergence of infectious diseases and increasing the number of individuals that have affected their immune competence has be come a challenge. Furthermore, considering the genus Aspergillus, as an etiologic agent of infection, which causes significant morbidity and mortality in immunocompromised patients. We present a case of a female preschool 3 years and 8 months with a history of matureteratoma fetiforme, who after 6 months of excision, compute dtomography (CT) scan control is performed where central bronchiectasis are evident with tubular opacities and saculares bronchial distribution, located mainly in the upper lobe of left chest, decreased left lung volume with incipient displacement of the heart and medistino left and low left pleural effusion, physical examination no alterations to income, so you enter with diagnosis of granulomatous disease study. antigen detection galactomannan reporting positive in two determinations so the diagnosis of invasive pulmonary aspergillosis rethinks meets voriconazole for 21 days, with significant improvement of lunglesions in chest CT scan, graduating with itraconazole therapy is performed to meet for 6 weeks. The early initiation of treatmentis a fundamental prognostic factor of invasive aspergillosis, constituting the first line in voriconazole(AU)
Assuntos
Humanos , Feminino , Pré-Escolar , Pneumonia , Teratoma , Itraconazol , Aspergilose Pulmonar Invasiva , Pediatria , Tomografia Computadorizada por Raios X , Doenças Transmissíveis , Morbidade , Mortalidade , Voriconazol , HospitaisRESUMO
Resumen Presentamos el caso clínico de una infección fúngica invasora con una conjuntivitis necrosante, escleritis y panuveitis unilateral por Scedosporium apiospermum en una mujer de 78 años con artritis reumatoidea con neutropenia secundaria a fármacos. El diagnóstico etiológico fue confirmado por cultivo micológico de secreción ocular con apoyo de MALDI-TOF-TOF e histopatología. El tratamiento incluyó aseos quirúrgicos asociado a terapia tópica y sistémica con voriconazol y corticoesteroides, con una evolución favorable a los dos meses de tratamiento. Una recaída obligó a un segundo curso terapéutico por 12 meses adicionales con mejoría y erradicación del agente. La conjuntivitis fúngica por S. apiospermum es un evento infrecuente asociado a pacientes inmunocomprometidos. Su tratamiento involucra desbridamientos quirúrgicos y terapia antifúngica prolongada.
Abstract We report a case of invasive fungal infection with necrotizing conjunctivitis, scleritis and unilateral panuveitis caused by Scedosporium apiospermum in a 78-year-old woman that developed neutropenia by drugs indicated for rheumatoid arthritis. The etiological diagnosis was confirmed by mycological culture of an ocular secretion with the support of MALDI-TOF-TOF analysis and histopathological findings. The treatment involved surgical debridements together with topical solution and systemic therapy with voriconazole and steroids with a favorable evolution after 2 months of treatment. A relapse required a second therapeutic course for an additional 12 months with improvement and eradication of the agent. Fungal conjunctivitis due to S. apiospermum is a rare event associated with immunosuppressed patients. Its treatment involves surgical debridements and prolonged antifungal therapy.
Assuntos
Humanos , Feminino , Idoso , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Hospedeiro Imunocomprometido , Voriconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
INTRODUCCIÓN: las infecciones fúngicas ocasionadas por levaduras del género Cándida son extremadamente comunes en mujeres de edad reproductiva, y constituyen un motivo de atención medica de salud. OBJETIVO: evaluar la susceptibilidad de Cándidas spp, mediante el método colorimétrico (Integral Yeast System Plus). MÉTODO: fue de tipo descriptivo, transversal; se recopiló información mediante observación directa en campo y el análisis documental para obtener información bibliográfica de tipo secundaria. RESULTADOS: de los 72 casos encontrados de Cándida Albicans revela que son susceptibles a la anfotericina B (2ug/ml); de los 5 casos encontrados de Cándida Krusei revela que son sensibles a la Anfotericina B (2ug/ml); De 1 caso encontrado de Cándida Parapsilosis revela sensibilidad en la Nistatina (1.25ug/ml). En este estudio la prevalencia de la infección por Cándida fue del (44.98%). CONCLUSIONES: Cándida Albicans fue la especie más común aislada en las mujeres embarazadas representando un 72%, En la evaluación de la susceptibilidad a través del kit Integral System Yeast Plus se obtuvo que Cándida Albicans es susceptible a Anfotericina B, Flucitosina entre otros, en Cándida Glabrata se obtuvo que es sensible a la Nistatina, Anfotericina B, susceptible entre otros, en Cándida Krusei se obtuvo que es sensible a la Anfotericina B, Clotrimazol, Miconazol, susceptibles a la Nistatina, Voriconazol y resistente a la Flucitosina, Ketoconazol, Itraconazol y Fluconazol.
INTRODUCTION: fungal infections caused by yeast of the genus Candida are extremely common in women of reproductive age, and constitute a reason for medical health care. OBJECTIVE: to evaluate the susceptibility of Candida spp, using the colorimetric method (Integral Yeast System Plus). METHOD: it was descriptive, transversal; Information was collected through direct observation in the field and documentary analysis to obtain secondary bibliographic information. RESULTS: of the 72 cases found, Candida Albicans reveals that they are susceptible to amphotericin B (2ug / ml); of the 5 cases found, Candida Krusei reveals that they are sensitive to Amphotericin B (2ug / ml); Of 1 case found of Candida Parapsilosis reveals sensitivity in Nystatin (1.25ug / ml). In this study, the prevalence of Candida infection was (44.98%). CONCLUSIONS: Candida Albicans was the most common species isolated in pregnant women, representing 72%. In the evaluation of susceptibility through the Integral System Yeast Plus kit it was obtained that Candida Albicans is susceptible to Amphotericin B, Flucytosine among others, in Candida Glabrata was obtained that it is sensitive to Nystatin, Amphotericin B, susceptible among others, in Candida Krusei it was obtained that it is sensitive to Amphotericin B, Clotrimazole, Miconazole, susceptible to Nystatin, Voriconazole and resistant to Flucytosin, Ketoconazole, Itraconazole and Fluconazole.
INTRODUÇÃO: as infecções fúngicas causadas por leveduras do gênero Candida são extremamente comuns em mulheres em idade reprodutiva e constituem motivo de cuidados médicos. OBJETIVO: avaliar a suscetibilidade de Candida spp, por meio do método colorimétrico (Integral Yeast System Plus). MÉTODO: foi descritivo, transversal; as informações foram coletadas por meio de observação direta em campo e análise documental para obtenção de informações bibliográficas secundárias. RESULTADOS: Dos 72 casos encontrados, Cândida Albicans revelou ser suscetíveis à anfotericina B (2ug /ml); dos 5 casos encontrados, Candida Krusei revela que são sensíveis à Anfotericina B (2ug / ml); de 1 caso encontrado de Candida Parapsilosis revela sensibilidade na Nistatina (1,25ug / ml). Neste estudo, a prevalência de infecção por Candida foi (44,98%). CONCLUSÕES: Cândida Albicans foi a espécie mais comum isolada em gestantes, representando 72%. Na avaliação da susceptibilidade através do kit Integral System Yeast Plus foi obtido que Candida Albicans é suscetível à Anfotericina B, Flucitosina entre outras, em Cândida Glabrata foi obtido que é sensível a Nistatina, Anfotericina B, suscetível entre outras, em Candida Krusei foi obtido que é sensível a Anfotericina B, Clotrimazol, Miconazol, suscetível a Nistatina, Voriconazol e resistente a Flucitosina, Cetoconazol, Itraconazol e Fluconazol.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Candida , Candida albicans , Anfotericina B , Colorimetria , Candida glabrata , Gestantes , Fluconazol , Prevalência , Clotrimazol , Itraconazol , Voriconazol , Flucitosina , Candida parapsilosis , Infecções , MiconazolRESUMO
Abstract This report presents the case of a 13-year-old female patient with history of acute myeloid leukemia, who, after a bone marrow transplant, began to vomit and experienced rapidly progressive deterioration of consciousness, in addition to disseminated erythematous-violaceous macules, and some blisters with hemorrhagic content inside. Skin biopsy evidenced intravascular filamentous structures. A blood culture confirmed the presence of Fusarium oxysporum. Intravenous treatment with voriconazole was initiated. The patient evolved unfavorably with multiple necrotic skin lesions, ischemic brain lesions, and death.
Assuntos
Humanos , Feminino , Adolescente , Fusariose/diagnóstico , Fusariose/tratamento farmacológico , Fusarium , Transplante de Medula Óssea , Voriconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
Abstract Fusariosis is a superficial or systemic infection, which occurs mainly in immunocompromised hosts, especially in patients with hematological neoplasia; 70%-75% of the cases present cutaneous manifestations. The disseminated form is rare and difficult to diagnose; even with specific treatment, the evolution is usually fatal. Currently, it is considered an emerging disease; in some centers, it is the second most common cause of invasive mycosis, after aspergillosis. The authors describe a case of a female patient with idiopathic bone marrow aplasia and disseminated fusariosis, who initially appeared to benefit from voriconazole and amphotericin B; however, due to persistent neutropenia, her clinical condition deteriorated with fatal evolution.
Assuntos
Humanos , Feminino , Fusariose , Fusarium , Medula Óssea , Hospedeiro Imunocomprometido , Voriconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
Resumo É apresentado o caso de uma paciente do sexo feminino, 77 anos, internada por pielonefrite e tratada com antibóticos de amplo espectro, tendo desenvolvido endoftalmite endógena bilateral presumida por Candida. Foi submetida à vitrectomia via pars plana e injeção intravítrea de anfotericina B, além de voriconazol oral. São abordados, ainda, os aspectos clínicos da endoftalmite endógena por meio de revisão da literatura.
Abstract A 77 year-old female patient suffering from pyelonephritis developed bilateral endogenous endophthalmitis presumed by Candida after have been treated with global spectrum antibiotics. Early vitrectomy and intravitreal amphotericin B injection were performed, in addition to oral voriconazole. Clinical aspects of endogenous endophthalmitis are also pointed out by a literature review.
Assuntos
Humanos , Masculino , Feminino , Idoso , Vitrectomia , Candida albicans , Infecções Oculares Fúngicas/tratamento farmacológico , Anfotericina B/uso terapêutico , Endoftalmite/cirurgia , Endoftalmite/tratamento farmacológico , Injeções Intravítreas , Voriconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
Resumen Los azoles son fármacos que inhiben la enzima 14α-esteroldemetilasa, impidiendo la unión de ergosterol; esto altera la estructura y función de la pared celular fúngica. Especialmente el grupo de los triazoles: fluconazol, itraconazol, voriconazol, posaconazol e isavuconazol, son una alternativa farmacológica para el tratamiento de la enfermedad fúngica invasora causada por Aspergillus spp, Candida spp, Cryptococcus spp, patógenos emergentes como los Mucorales, y de micosis endémicas como las ocasionadas por Histoplasma spp y Coccidioides spp. Los efectos adversos de los triazoles son menos frecuentes comparados con los ocasionados por anfotericina B, un antifúngico de uso común para estas micosis. Los principales efectos adversos de los triazoles son hepáticos, gastrointestinales y cardiovasculares como la prolongación del intervalo QT. Las interacciones farmacológicas son usuales y se presentan con moléculas que usan sustratos del citocromo CYP3A4, lo que incluye anti-retrovirales, anti-tuberculosos e inmunomoduladores. En este trabajo se revisan la historia, características farmacológicas y los ensayos clínicos que evidencian su eficacia clínica en los diferentes escenarios clínicos.
Abstract The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.
Assuntos
Azóis/farmacologia , Testes de Sensibilidade Microbiana , Fluconazol , Itraconazol , Farmacorresistência Fúngica , Voriconazol , AntifúngicosRESUMO
Criptococose é uma doença grave que afeta tanto imunocomprometidos quanto imunocompetentes, com isso analisar a virulência é fundamental para novas terapêuticas. Objetivo: Analisar a capacidade de virulência e susceptibilidade aos antifúngicos de Cryptococcus spp. isolados de líquor de pacientes de hospital do norte do Paraná. Métodos: A partir de dois isolados clínicos C. neoformans e C. gattii, realizou-se a confirmação da identificação. Para a virulência, avaliou-se o tamanho da cápsula, capacidade de sobrevivência após exposição a neutrófilos, produção de melanina e urease. No antifungigrama por difusão em disco utilizou-se: anfotericina B, cetoconazol, voriconazol, itraconazol e miconazol. Resultados: C. gattii destaca-se por maior desenvolvimento da cápsula além da melhor capacidade de sobreviver a fagocitose em relação ao C. neoformans. No antifungigrama, ambos os isolados se apresentam sensíveis às drogas estudadas. Conclusão: Esses achados contribuem para a compreensão das diferentes patogêneses entre C. gattii e C. neoformans.
Cryptococcosis is a serious disease that can affect both immunocompromised and immunocompetent individuals, thus the virulence analysis is fundamental for the development of new treatments. Objective: To analyze the virulence and susceptibility of Cryptococcus spp. isolated from cerebrospinal fluid of patients from a hospital in the north of Paraná. Methods: From two clinical isolates, C. neoformans and C. gattii were confirmed and identified. For virulence, capsule size, survival capacity after exposure to neutrophils, melanin production and urease were evaluated. In the disc-diffusion method, the following antifungals were used: amphotericin B, ketoconazole, voriconazole, itraconazole and miconazole Results: It was observed that C. gattii presents greater results for development of the capsule beside presenting the best ability to survive phagocytosis in relation to C. neoformans. In the disc-diffusion method, both isolates presented sensitivity to the studied drugs. Conclusion: These findings contribute to the understanding of the different pathogens between C. gattii and C. neoformans.