RESUMEN
The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Histoplasmosis/sangre , Histoplasmosis/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Antígenos Fúngicos/orina , Brasil/epidemiología , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Infecciones por VIH/virología , Histoplasma/inmunología , Histoplasmosis/epidemiología , Histoplasmosis/inmunología , Humanos , Inmunoensayo/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Centros de Atención TerciariaRESUMEN
OBJECTIVE: The purpose of the present, prospective, cohort study was to monitor urine cytology samples from recipients of renal transplants to search for the occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to correlate the existence of these cells with molecular detection of polyomavirus BK (BKV) DNA in urine. MATERIAL AND METHODS: This study included patients who underwent renal transplantation. Patients had their urine tested quarterly, during the first year post-transplantation, for the presence of decoy cells and degenerated cells, as well as by quantitative determination of BKV load in the urine and plasma. RESULTS: Three hundred and sixty-one examinations were performed on 101 patients within 12 months of attendance. Urine cytology results were: 198 (54.9%) negative and 60 (16.6%) positive for the presence of viral cytopathic effects depending on the presence of BKV infection, 72 (19.9%) positive for the manifestation of degenerated cells and 31 (8.6%) unsatisfactory for analysis. There was a subtle tendency towards the presence of degenerated inclusion-bearing cells in cases in which the virus was detected in voided urine. However, the presence of degenerated cells exhibited a tendency to BKV positivity in months 3, 6 and 9 and, exclusively in month 12, this trend was statistically significant. CONCLUSIONS: There were not enough strong morphological and staining elements to state the origin of the degenerated cells or to describe the nature of the infection (viral or bacterial), given that these cells were undergoing an apoptotic process in post renal transplant patients.
Asunto(s)
Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/virología , Adolescente , Adulto , Anciano , Virus BK/aislamiento & purificación , Citodiagnóstico/métodos , Femenino , Humanos , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/orina , Estudios Prospectivos , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/orina , Infecciones Tumorales por Virus/virología , Adulto JovenRESUMEN
To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.
Asunto(s)
Antifúngicos/farmacología , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus fumigatus/efectos de los fármacos , Azoles/farmacología , Farmacorresistencia Fúngica , Vigilancia de la Población , Aspergillus fumigatus/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Prevalencia , Estudios ProspectivosRESUMEN
Previous studies have demonstrated reduced virulence in the species that comprise the Candida parapsilosis complex. We investigated a cohort of 93 patients with candidemia caused by this complex. Most infections were caused by C. parapsilosis (80.6%), followed by C. orthopsilosis (18.3%) and C. metapsilosis (1.1%). Renal failure (P < 0.001) and chronic liver diseases (P = 0.019) were more frequently encountered with infections caused by the C. orthopsilosis group, suggesting an association with patients who had a greater state of immune suppression in comparison with infections caused by C. parapsilosis sensu stricto.
Asunto(s)
Candida/clasificación , Candida/aislamiento & purificación , Candidemia/epidemiología , Candidemia/microbiología , Candidemia/complicaciones , Estudios de Cohortes , Humanos , Hepatopatías/epidemiología , Hepatopatías/etiología , Prevalencia , Insuficiencia Renal/epidemiología , Insuficiencia Renal/etiología , Medición de Riesgo , Factores de RiesgoRESUMEN
Respiratory viral infections are frequent causes of morbidity in transplant patients. We screened symptomatic adult transplant recipients for respiratory viruses in a cohort of patients attending a referral medical center in Brazil. The duration of viral shedding and the prevalence of viral codetections were also determined. During a 1-year period (2011-2012), swabs were obtained from 50 patients. An in-house polymerase chain reaction panel designed to detect 10 viruses was used. Viruses were identified in 19 (38%) patients, particularly parainfluenza III (32%) and the respiratory syncytial virus (20%); multiple viruses were identified in 26% of patients. Prolonged viral shedding was observed with 60% of individuals excreting viruses for >10 days. The clinical and epidemiologic relevance of prolonged viral shedding remains to be determined.
Asunto(s)
Rechazo de Injerto/prevención & control , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Trasplante de Órganos , Infecciones del Sistema Respiratorio/transmisión , Virosis/transmisión , Esparcimiento de Virus , Adulto , Anciano , Estudios de Cohortes , Coinfección , Femenino , Humanos , Virus de la Influenza A/genética , Virus de la Influenza B/genética , Gripe Humana/inmunología , Gripe Humana/transmisión , Trasplante de Riñón , Trasplante de Hígado , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Virus de la Parainfluenza 1 Humana/genética , Virus de la Parainfluenza 2 Humana/genética , Virus de la Parainfluenza 3 Humana/genética , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/transmisión , Virus Sincitiales Respiratorios/genética , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Infecciones por Respirovirus/inmunología , Infecciones por Respirovirus/transmisión , Factores de Tiempo , Virosis/inmunología , Virosis/virología , Adulto JovenRESUMEN
Invasive fungal diseases have emerged as important causes of morbidity and mortality in haematological patients. In this study air samples were collected in two haematopoietic stem cell transplantation (HSCT) units, in which distinct air-control systems were in place. In hospital 1 no high-efficiency particulate air (HEPA) filter was available whereas in hospital 2 HSCT rooms were equipped with HEPA filters, with positive air pressure in relation to the corridor. A total of 117 samples from rooms, toilets and corridors were obtained during December 2009 to January 2011, using a six-stage Andersen sampler. In both hospitals, the concentration of potentially pathogenic fungi in the air was reduced in patients' rooms compared to corridors (P < 0·0001). Despite the presence of a HEPA filter in hospital 2, rooms in both hospitals showed similar concentrations of potentially pathogenic fungi (P = 0·714). These findings may be explained by the implementation of additional protective measures in hospital 1, emphasizing the importance of such measures in protected environments.
Asunto(s)
Microbiología del Aire , Aspergillus/aislamiento & purificación , Hongos/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas , Unidades Hospitalarias , Control de Infecciones , Esporas Fúngicas/aislamiento & purificación , Filtros de Aire , Movimientos del Aire , Infección Hospitalaria/prevención & control , Humanos , Micosis/prevención & control , Habitaciones de PacientesRESUMEN
Aspergillomas develop from progressive layers of mycelial growth on the walls of pulmonary cavities over months. Aspergillomas are characteristic of chronic pulmonary aspergillosis and are a risk factor for azole resistance. We investigated genotypic and phenotypic alterations in Aspergillus fumigatus recovered from aspergillomas. Aspergillomas were removed from three patients (two at surgery, one at autopsy) and dissected. Overall 92 colonies of A. fumigatus were isolated. Microsatellite typing was conducted to determine genetic type. Itraconazole, voriconazole and posaconazole susceptibilities were performed. The cyp51A gene was sequenced in 22 isolates. Isolates from Patient 1 (n = 25) were azole susceptible and resistant, although all cyp51A sequences were wild type, the isolates split into two distinct clades. In Patient 2, isolates were less variable (n = 10), all were azole susceptible. In Patient 3 only azole-resistant strains (n = 57) were isolated, with M220K or M220T Cyp51A alterations, and microevolution was indicated. Marked diversity was observed in isolates from these patients; revealing differences in azole susceptibility, mechanism of resistance and genetic type. Importantly, routine sampling from respiratory specimens proved suboptimal in all cases; azole resistance was missed (Patient 1), cultures were negative (Patient 2) and high-level posaconazole resistance was not detected (Patient 3).
Asunto(s)
Aspergillus fumigatus/clasificación , Aspergillus fumigatus/genética , Variación Genética , Aspergilosis Pulmonar/microbiología , Adulto , Antifúngicos/farmacología , Aspergillus fumigatus/aislamiento & purificación , Enfermedad Crónica , Femenino , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Repeticiones de Microsatélite , Persona de Mediana Edad , Tipificación Molecular , Técnicas de Tipificación Micológica , Pirimidinas/farmacología , Triazoles/farmacología , VoriconazolRESUMEN
Yerba mate (Ilex paraguariensis) infusion is a very popular drink in South America. Although several studies have evaluated the potential for fungal contamination in foodstuff, very few investigations have been conducted with yerba mate samples. In order to evaluate for the presence of potentially pathogenic fungi, here we studied 8 brands of yerba mate commercially available in Southern Brazil. Fungal survival in adverse conditions such as gastric pH was determined by incubating samples at pH 1.5. Because hot water is generally used to prepare yerba mate infusion, the effect of several temperatures on fungal growth was also investigated. All but 1 yerba mate brand showed substantial fungal growth, in the range of <104900 colony-forming units per gram. Some of these fungi were able to survive extreme variations in pH and temperature. Because of the potential for yerba mate to carry pathogenic fungi, immunocompromised patients may be at risk of acquiring invasive fungal diseases by drinking yerba mate infusion.
Asunto(s)
Bebidas/microbiología , Contaminación de Alimentos , Hongos/aislamiento & purificación , Ilex paraguariensis/microbiología , Micosis/microbiología , Aspergillus fumigatus/aislamiento & purificación , Aspergillus niger/aislamiento & purificación , Humanos , Factores de Riesgo , Células MadreRESUMEN
Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs penetrate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new antifungal agents: isavuconazole, ravuconazole, albaconazole and aminocandin. Isavuconazole and ravuconazole are extremely similar, with a broad spectrum of activity, a very long half-life and large volume of distribution and good in vivo data supporting their efficacy in invasive aspergillosis and candidosis. Both compounds are in early Phase 3 development. Albaconazole has also shown very potent activity against species of Candida, Cryptococcus and Aspergillus. It was well tolerated and effective in women with vaginal candidosis. Aminocandin is an intravenous-only echinocandin with in vivo activity against Candida spp. and Aspergillus spp. Its extended half-life probably permits dosing less frequently than once a day. Overall these new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. Their antifungal spectrum is narrower than posaconazole and probably similar to voriconazole (isavuconazole and ravuconazole) and caspofungin (aminocandin). Licensure and determination of their place in clinical practice requires randomized clinical studies, which are or will be underway.
Asunto(s)
Antifúngicos/química , Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Animales , Antifúngicos/farmacología , Farmacorresistencia Fúngica/efectos de los fármacos , Farmacorresistencia Fúngica/fisiología , Humanos , Micosis/microbiología , Quinazolinas/química , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Estereoisomerismo , Triazoles/química , Triazoles/farmacología , Triazoles/uso terapéuticoRESUMEN
The issue of central venous catheter (CVC) removal in adult patients with candidaemia remains controversial. Although removal of CVCs has been advocated as an adjunctive strategy for treating patients with candidaemia, most studies have failed to control for important variables, e.g., the severity of illness and persistence of neutropenia. Multivariate analysis has failed to identify a significant effect of CVC removal on the prognosis for patients with candidaemia. A properly designed randomised trial that controls for confounding variables is necessary to clarify the importance of CVC removal in such patients. Until this evidence is available, systematic removal of all CVCs in these patients seems not to be justified.
Asunto(s)
Candidiasis/terapia , Cateterismo Venoso Central/efectos adversos , Fungemia/terapia , Atención al Paciente/métodos , Adulto , Humanos , Resultado del TratamientoAsunto(s)
Virus BK/aislamiento & purificación , Nefritis Lúpica/virología , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/virología , Adolescente , Femenino , Humanos , Cuerpos de Inclusión Viral/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones Tumorales por Virus/diagnóstico , Urinálisis/métodos , Orina/virología , Activación ViralRESUMEN
While invasive aspergillosis occurs typically in severely immunocompromised patients, cases of surgical site infection have been reported in immunocompetent individuals. The Medline, LILACS and EMBASE databases were searched for descriptions of cases of post-operative aspergillosis, and references from relevant articles and conference abstracts were reviewed. More than 500 cases of post-operative aspergillosis were found. Cardiac surgery (n = 188), ophthalmological surgery (n > 90) and dental surgery (n > 100) were associated with the majority of cases. Other cases involved wound infections (n = 22), bronchial infections (n = 30), mediastinitis (n = 11), pleural aspergillosis (n = 1), infections following orthopaedic surgery (n = 42), vascular prosthetic surgery (n = 22), breast surgery (n = 5), abdominal surgery (n = 10) and neurosurgery (n = 25). In most patients, the source was presumed to be airborne infection during the surgical procedure. Prevention of these infections requires special care of the ventilation system in the operating room. Successful treatment requires rapid diagnosis, surgical debridement and antifungal therapy, often with voriconazole. In order to improve the outcome, better diagnostic methods are needed, particularly for cases of endocarditis and aortitis.
Asunto(s)
Aspergilosis , Aspergillus/aislamiento & purificación , Complicaciones Posoperatorias , Microbiología del Aire , Aspergilosis/diagnóstico , Aspergilosis/etiología , Aspergilosis/prevención & control , Aspergilosis/terapia , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/microbiología , Infección Hospitalaria/etiología , Infección Hospitalaria/microbiología , Oftalmopatías/etiología , Oftalmopatías/microbiología , Humanos , Quirófanos/normas , Factores de Riesgo , Tratamiento del Conducto Radicular/efectos adversos , Sinusitis/etiología , Sinusitis/microbiología , Ventilación/normas , Infección de Heridas/etiología , Infección de Heridas/microbiologíaRESUMEN
Candidaemia is perceived as a nosocomial infection. The aim of this study was to describe all cases of candidaemia that occurred in the outpatient setting, and to compare risk factors and outcome among patients with outpatient-acquired and nosocomial candidaemia. During 1995 and 2003, 210 patients developed candidaemia at our institution, and 9.0% were outpatient acquired. Major underlying diseases were cancer (47.4%) and chronic renal failure (36.8%). Most occurred within 24 h of hospitalization (63.2%), and 83.7% were caused by species other than Candida albicans, mainly Candida parapsilosis (36.8%). Candida spp. were isolated from catheters in 21% of cases, and 52.6% of patients had been admitted to hospital in the 60 days preceding candidaemia. Compared with patients with nosocomial candidaemia, chronic renal failure was more frequent in the outpatient group, who were also more commonly exposed to haemodialysis. Ileus, gastrointestinal bleeding, previous bacteraemia, use of proton pump inhibitors, previous stay in the intensive care unit and requirement for antibiotics, blood transfusion, vasopressors and invasive medical procedures were more frequent in the nosocomial group. Overall mortality was high in both groups. Candidaemia must be considered as a potential cause of sepsis in the community, and it is associated with a high mortality rate.
Asunto(s)
Candidiasis/etiología , Infecciones Comunitarias Adquiridas/etiología , Infección Hospitalaria/etiología , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Brasil/epidemiología , Candidiasis/epidemiología , Candidiasis/terapia , Niño , Preescolar , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/terapia , Infección Hospitalaria/epidemiología , Infección Hospitalaria/terapia , Complicaciones de la Diabetes/complicaciones , Femenino , Hemorragia Gastrointestinal/complicaciones , Mortalidad Hospitalaria , Humanos , Lactante , Control de Infecciones , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Pacientes Ambulatorios/estadística & datos numéricos , Vigilancia de la Población , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI), a liver-produced coagulation factor, has been associated with higher mortality in cirrhotic patients, but there has not been any description of its role in perioperative care in liver transplantation cases. METHODS: A total of 21 patients were included. Serum TAFI levels were determined at 3 time points: preoperatively (TAFI pre), immediately postoperative (TAFI PO), and 24 hours postoperatively (TAFI 24 h). The main outcome was the physiological pattern of TAFI in the perioperative period of liver transplantation. The secondary outcomes were the association between TAFI and early allograft dysfunction (EAD) as well as that of TAFI and 6-month mortality. RESULTS: TAFI levels increased at the 24-hour time point, compared to the other 2 time points (TAFI pre, P = .007; TAFI PO, P = .0001). Early allograft dysfunction occurred in 2 of 21 patients, both demonstrating lower TAFI 24 h levels compared to those who did not develop this complication (3.0 ± 0.2 vs 1.5 ± 0.3; P = .0001). Three patients who died all demonstrated lower levels of TAFI pre (1.3 ± 0.1 vs 2.5 ± 0.5; P = .001) and TAFI PO (1.2 ± 0.1 vs 2.4 ± 0.4; P = .001) compared to the survivors. CONCLUSIONS: These findings suggest that the determination of TAFI levels-both pre- and postoperatively-may be of clinical relevance in liver transplant recipients.
Asunto(s)
Carboxipeptidasa B2/metabolismo , Trasplante de Hígado , Hígado/metabolismo , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Cirrosis Hepática/metabolismo , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Proyectos Piloto , PronósticoRESUMEN
BACKGROUND: Tuberculosis (TB) is associated with high morbidity and mortality in solid organ transplant (SOT) recipients. Also, SOT patients have a 20- to 74-fold increase in the chance of developing TB compared to the general population. Here we evaluated the incidence of hepatotoxicity in SOT recipients on treatment for TB and determined risk factors for liver toxicity in these patients. PATIENTS AND METHODS: Retrospective cohort conducted in a reference hospital for SOT in Southern Brazil. All SOT recipients who underwent TB treatment during the years 2000-2012 were considered for the study. RESULTS: A total of 69 patients were included in the study and 23 had liver toxicity (incidence 33.3%). Independent risk factors for hepatotoxicity were rifampin use at doses of ≥600 mg daily (P = .016; OR 2.47; 95% CI, 1.18-5.15) and lung transplantation (P = .017; OR 2.05; 95% CI, 1.14-3.70). Kidney transplantation appeared as a protective factor (P = .036; OR 0.50; 95% CI, 0.26-0.96). Mortality was higher in the patients who had hepatotoxicity (43.5%), compared with those who did not (19.6%). CONCLUSION: In this study, the use of rifampin at doses of 600 mg daily or higher was found to be an independent risk factor for liver toxicity in SOT recipients. The importance of additional risk factors for hepatotoxicity, such as lung transplantation as well as the protective role of kidney transplantation, should be better investigated in SOT recipients being treated for TB.
Asunto(s)
Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Trasplante de Órganos , Tuberculosis/tratamiento farmacológico , Antituberculosos/uso terapéutico , Brasil/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Tuberculosis/epidemiología , Tuberculosis/microbiologíaRESUMEN
Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.
Asunto(s)
Antifúngicos/uso terapéutico , Fusariosis/tratamiento farmacológico , Fusariosis/epidemiología , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Niño , Preescolar , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Quimioterapia Combinada/métodos , Femenino , Fusariosis/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Voriconazol/uso terapéutico , Adulto JovenRESUMEN
Oral azole antifungal therapy is used extensively for all forms of aspergillosis, including allergic bronchopulmonary aspergillosis (ABPA). However, long-term therapy may increase the risk of resistance. Here we report itraconazole and voriconazole resistance with reduced susceptibility to posaconazole in Aspergillus fumigatus in two patients exposed to itraconazole. Patients were diagnosed with ABPA and Aspergillus bronchitis related to innate immune defects. An azole susceptible strain was initially isolated from patient 1, but later a genetically different azole-resistant strain was cultured, possibly related to sub-therapeutic itraconazole levels, which could be a trigger for selection of resistance. The mechanism of resistance identified in this case was an L98H change in Cyp51A, accompanied by a tandem repeat in the promoter region of cyp51A leading to increased expression. No cyp51A mutation was found in azole-resistant isolates recovered from patient 2. Both patients responded to posaconazole, with plasma levels of >1.0 mg/L. Subsequently, susceptible strains of different molecular types were cultured from both patients, suggesting eradication and replacement.
Asunto(s)
Antifúngicos/farmacología , Aspergilosis Broncopulmonar Alérgica/microbiología , Aspergillus fumigatus/efectos de los fármacos , Azoles/farmacología , Bronquitis/microbiología , Farmacorresistencia Fúngica , Adulto , Sustitución de Aminoácidos/genética , Antifúngicos/uso terapéutico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Aspergillus fumigatus/aislamiento & purificación , Azoles/uso terapéutico , Bronquitis/tratamiento farmacológico , Sistema Enzimático del Citocromo P-450/genética , Femenino , Proteínas Fúngicas/genética , Humanos , Itraconazol/farmacología , Persona de Mediana Edad , Mutación Missense , Plasma/química , Pirimidinas/farmacología , Triazoles/farmacología , Triazoles/uso terapéutico , VoriconazolRESUMEN
This study aims to compare the concentration of viable fungi, especially those of the genus Aspergillus in the respiratory tract of stabled horses with and without Recurrent Airway Obstruction (RAO). Thirty two housed horses from four equestrian centers in Brazil were included in the study. These animals were submitted to clinical examination and to a respiratory sample collection. They were categorized into two groups: healthy and RAO-affected horses. Samples obtained by tracheobronchial washes were evaluated for fungal microscopy, quantitative culture and Aspergillus spp. quantification. Eighteen healthy and 14 RAO-affected horses were studied. Fungi were more frequently recovered in the RAO group, in comparison to controls, for both fungal microscopy (P<0.0001), fungal culture (P<0.0001) and Aspergillus spp. quantitative culture (p=0.001). In conclusion, horses with RAO have significantly higher fungal load in the respiratory tract in comparison to healthy horses. The implications of these findings in terms of the pathogenesis of RAO deserve additional investigation...
Este estudo objetivou comparar a concentração de fungos viáveis, especialmente do gênero Aspergillus, no trato respiratório de equinos estabulados com e sem obstrução recorrente das vias aéreas (ORVA). Trinta e dois equinos provenientes de quatro centros de treinamento equestre do Brasil foram incluídos no estudo. Os animais foram submetidos a exame clínico e coleta de amostra respiratória, sendo categorizados em dois grupos: sadios e ORVA. Os lavados traqueobrônquicos obtidos foram avaliados por exame micológico direto e cultivo quantitativo. Ao todo, 18 equinos saudáveis e 14 com ORVA foram estudados. Fungos foram mais frequentemente detectados em amostras do grupo ORVA em comparação com o grupo controle, tanto no exame micológico direto (P<0,0001) e cultivo quantitativo (P<0,0001) quanto na concentração de unidades formadoras de colônias (UFC) de Aspergillus spp. isolada em cultivo (p=0,001). Equinos com ORVA têm maior concentração de propágulos fúngicos no trato respiratório em comparação com animais sadios. As implicações desses achados na patogenia da ORVA merecem maior atenção e investigação...
Asunto(s)
Animales , Aspergillus/aislamiento & purificación , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/veterinaria , Equidae/anomalías , Hongos , Hipersensibilidad/veterinaria , Obstrucción de las Vías Aéreas/veterinariaRESUMEN
An interlaboratory study was performed with the aim of investigating the reproducibility of a multiplex microbial microsatellite-based typing assay for Aspergillus fumigatus in different settings using a variety of experimental and analytical conditions and with teams having variable prior microsatellite typing experience. In order to circumvent problems with exchange of sizing data, allelic ladders are introduced as a straightforward and universally applicable concept for standardization of such typing assays. Allelic ladders consist of mixtures of well-characterized reference fragments to act as reference points for the position in an electrophoretic trace of fragments with established repeat numbers. Five laboratories independently analysed six microsatellite markers in 18 samples that were provided either as DNA or as A. fumigatus conidia. Allelic data were reported as repeat numbers and as sizes in nucleotides. Without the use of allelic ladders, size differences of up to 6.7 nucleotides were observed, resulting in interpretation errors of up to two repeat units. Difficulties in interpretation were related to non-specific amplification products (which were resolved with explanation) and bleed-through of the different fluorescent labels. In contrast, after resolution of technical or interpretive problems, standardization of sizing data by using allelic ladders enabled all participants to produce identical typing data. The use of allelic ladders as a routine part of molecular typing using microsatellite markers provides robust results suitable for interlaboratory comparisons and for deposition in a global typing database.
Asunto(s)
Aspergillus fumigatus/clasificación , Dermatoglifia del ADN/métodos , Dermatoglifia del ADN/normas , ADN de Hongos/genética , Repeticiones de Microsatélite , Técnicas de Tipificación Micológica/métodos , Técnicas de Tipificación Micológica/normas , Aspergillus fumigatus/genética , Dermatoglifia del ADN/estadística & datos numéricos , Genotipo , Técnicas de Tipificación Micológica/estadística & datos numéricos , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
Chronic pulmonary aspergillosis is broad term encompassing chronic cavitary, chronic fibrosing pulmonary aspergillosis and aspergilloma. All affect patients with structural lung diseases and many have subtle genetic immune defects. Almost all cases are caused by Aspergillus fumigatus. Here we report a patient with an aspergilloma which had Aspergillus flavus recovered from a surgical specimen and serum containing detectable precipitating antibody.