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1.
Artigo em Inglês | MEDLINE | ID: mdl-31932366

RESUMO

Our objective was to develop a population pharmacokinetic (PK) model in order to evaluate the currently recommended dosing regimen in term and preterm neonates. By using an optimal design approach, a prospective PK study was designed and implemented in 60 neonates with postmenstrual ages (PMA) of 26 to 43 weeks. A loading dose of 16 mg/kg was administered at day 1, followed by a maintenance dose of 8 mg/kg daily. Plasma concentrations were quantified by high-pressure liquid chromatography-mass spectrometry. Population PK (popPK) analysis was performed using NONMEM software. Monte-Carlo (MC) simulations were performed to evaluate currently recommended dosing based on a pharmacodynamic index of area under the concentration-time curve (AUC)/MIC ratio of ≥400. A two-compartment model with linear elimination best described the data by the following equations: clearance (CL) = 0.0227 × (weight [wt]/1,765)0.75 × (estimated creatinine clearance [eCRCL]/22)0.672, central compartment volume of distribution (V1) = 0.283 (wt/1,765), intercompartmental clearance (Q) = 0.151 (wt/1,765)0.75, and peripheral compartment volume (V2) = 0.541 (wt/1,765). The interindividual variability estimates for CL, V1, and V2 were 36.5%, 45.7%, and 51.4%, respectively. Current weight (wt) and estimated creatinine clearance (eCRCL) significantly explained the observed variability. MC simulation demonstrated that, with the current dosing regimen, an AUC/MIC ratio of ≥400 was reached by only 68.5% of neonates with wt of <1 kg when the MIC was equal to 1 mg/kg, versus 82.2%, 89.7%, and 92.7% of neonates with wt of 1 to <2, 2 to <3, or ≥3 kg, respectively. Augmentation of a maintenance dose up to 10 or 11 mg/kg for preterm neonates with wt of 1 to <2 or <1 kg, respectively, increases the probability of reaching the therapeutic target; the recommended doses seem to be adequate for neonates with wt of ≥2 kg. Teicoplanin PK are variable in neonates, with wt and eCRCL having the most significant impact. Neonates with wt of <2 kg need higher doses, especially for Staphylococcus spp. with an MIC value of ≥1 mg/liter.

2.
Clin Microbiol Infect ; 25(9): 1096-1113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158517

RESUMO

SCOPE: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children. METHODS: Review and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations. QUESTIONS: Questions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/normas , Aspergillus/efeitos dos fármacos , Criança , Gerenciamento Clínico , Monitoramento de Medicamentos , Humanos , Recém-Nascido
4.
Transplant Proc ; 51(2): 454-456, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879565

RESUMO

BACKGROUND: Infections due to extensively drug resistant Gram-negative bacteria (GNB) after solid organ transplantation are increasing in prevalence and are associated with high morbidity and mortality. Surveillance culture (SC) seems to be an important tool for extensively drug resistant GNB control. The aim of this study was to evaluate colonization rates and subsequent infections by XDR-GNB in liver transplant recipients. MATERIAL AND METHODS: This was a prospective cohort study in patients who underwent liver transplantation (LT) between January 2016 and January 2018. Data on demographics, extensively drug resistant colonization, and 3-month clinical outcomes were obtained. Colonization was defined as a positive surveillance culture (SC-perirectal) immediately before transplantation, once weekly after LT, and after intensive care unit discharge, with emphasis to carbapenem-resistant Gram-negative bacteria (CR-GNB). RESULTS: Forty-four patients who underwent LT were included in the study. Ten patients (22.72%) were colonized with CR-GNB prior to transplantation, and 7/10 (70%) developed infection due to the same pathogen (5 patients bloodstream infections, 2 patients pneumonia) during the study period. Intensive care unit length of stay was significantly longer in colonized with CR-GNB patients (P < .05). Mortality rate was higher in colonized patients (30%) than in noncolonized (11.76%) (P = .2). CONCLUSION: Our study results suggest an overall 70% risk of CR-GNB infection among colonized patients. Given the high mortality rate and the difficulty in treating these infections, further research to investigate and develop strategies to eliminate the colonization is needed.


Assuntos
Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/imunologia , Hospedeiro Imunocomprometido , Transplante de Fígado , Adulto , Idoso , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco
5.
J Hosp Infect ; 101(1): 53-59, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30059747

RESUMO

BACKGROUND: Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children. AIM: To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs). METHODS: Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms. FINDINGS: A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems. CONCLUSION: Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Monitoramento Epidemiológico , Sepse/epidemiologia , Adolescente , Benchmarking , Criança , Pré-Escolar , Fungos/classificação , Fungos/isolamento & purificação , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Grécia/epidemiologia , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva
6.
J Hosp Infect ; 99(4): 396-404, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29792971

RESUMO

BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CRGNB) infections constitute a global threat for critically ill patients and the outcome of their hospitalization. Early identification of CRGNB through rectal surveillance cultures and routine infection control measures including contact precautions, use of appropriate disinfectants, staff education on cleaning, and hand hygiene may reduce the dissemination of CRGNB. AIM: To assess the impact of enhanced infection control measures on CRGNB infections in a nine-bed polyvalent intensive care unit in a tertiary level hospital in an endemic area. METHODS: A quasi-experimental study, which included patients with CRGNB infection retrospectively for six months and those participating in an active surveillance programme prospectively for the subsequent 22 months. Active surveillance programme (weekly rectal swabs) was implemented including two sub-periods with infection control measures and enhanced infection control measures. CRGNB incidence, prevalence, colonization pressure, infections and compliance with infection control measures and enhanced infection control measures were recorded. Analysis was performed through time-series and interrupted time-series. FINDINGS: During the active surveillance programme, enhanced infection control measures led to a steeper downwards trend in incidence, prevalence, and colonization pressure for CRGNB compared to the infection control measures sub-period. The linear trend was for carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) infections to decrease from 19.6 to 8.1 infections per 1000 bed-days (IBD) (P = 0.001) and from 5.1 to 1.79 IBD (P = 0.043), respectively. By contrast, carbapenem-resistant Acinetobacter baumannii infections increased from 5.2 to 15.3 IBD (P = 0.001). CONCLUSION: Enhanced infection control measures including enhanced hand hygiene, active surveillance combined with contact precautions, education, audits and feedback policies and interventions could reduce CRKP and CRPA in endemic areas.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Monitoramento Epidemiológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Controle de Infecções/métodos , Resistência beta-Lactâmica , Acinetobacter baumannii/classificação , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Incidência , Unidades de Terapia Intensiva , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Prevalência , Estudos Prospectivos , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Adulto Jovem
7.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imagem por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
8.
Med Mycol ; 56(suppl_1): 93-101, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538730

RESUMO

The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common underlying disease in countries with high income and uncontrolled diabetes in developing countries. Clinical approach to diagnosis lacks sensitivity and specificity. Radiologically, multiple (≥10) nodules and pleural effusion are reportedly associated with pulmonary mucormycosis. Another finding on computerized tomography (CT) scan, which seems to indicate the presence of mucormycosis, is the reverse halo sign. Microscopy (direct and on histopathology) and culture are the cornerstones of diagnosis. Molecular assays can be used either for detection or identification of mucormycetes, and they can be recommended as valuable add-on tools that complement conventional diagnostic procedures. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Our armamentarium of antifungals is slightly enriched by the addition of two newer azoles (posaconazole and isavuconazole) to liposomal amphotericin B, which remains the drug of choice for the initial antifungal treatment, according to the recently published guidelines by ECIL-6, as well as those published by ECMM/ESCMID. Despite the efforts for better understanding of the pathogenesis, early diagnosis and aggressive treatment of mucormycosis, the mortality rate of the disease remains high.


Assuntos
Mucormicose/diagnóstico , Mucormicose/terapia , Antifúngicos/administração & dosagem , Terapia Combinada , Desbridamento , Diagnóstico por Imagem , Diagnóstico Precoce , Humanos , Técnicas Microbiológicas , Técnicas de Diagnóstico Molecular , Mucorales/efeitos dos fármacos , Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/microbiologia
9.
Clin Microbiol Infect ; 23(10): 776.e1-776.e5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28412383

RESUMO

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.


Assuntos
Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Prospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-26896312

RESUMO

The development and validation of an ultra-high pressure liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was performed with the aim to be applied for the quantification of plasma teicoplanin concentrations in neonates. Pharmacokinetic data of teicoplanin in the neonatal population is very limited, therefore, a sensitive and reliable method for the determination of all isoforms of teicoplanin applied in a low volume of sample is of real importance. Teicoplanin main components were extracted by a simple acetonitrile precipitation step and analysed on a C18 chromatographic column by a triple quadrupole MS with electrospray ionization. The method provides quantitative data over a linear range of 25-6400ng/mL with LOD 8.5ng/mL and LOQ 25ng/mL for total teicoplanin. The method was applied in plasma samples from neonates to support pharmacokinetic data and proved to be a reliable and fast method for the quantification of teicoplanin concentration levels in plasma of infants during therapy in Intensive Care Unit.


Assuntos
Antibacterianos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Teicoplanina/sangue , Monitoramento de Medicamentos/métodos , Humanos , Recém-Nascido , Limite de Detecção
12.
Transpl Infect Dis ; 18(5): 795-800, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27496079

RESUMO

We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic syndrome (HPS) in a 37-year-old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi-organ failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases).


Assuntos
Antivirais/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Glomerulonefrite por IGA/cirurgia , Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim/efeitos adversos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Antivirais/administração & dosagem , Diarreia/etiologia , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Evolução Fatal , Feminino , Febre/etiologia , Ganciclovir/administração & dosagem , Ganciclovir/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Insuficiência de Múltiplos Órgãos/mortalidade , Oligúria/etiologia
13.
Hippokratia ; 20(4): 274-278, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29416299

RESUMO

BACKGROUND: The elderly represent a significant cohort of patients presenting at the emergency department, especially in the developed countries. They are characterized by impaired physical condition, comorbidities, and little immune system resources and make frequent use of the healthcare system and its facilities. This study aimed to describe the features and prognostic factors of sepsis in elderly patients (>60 years old) admitted to an internal medicine ward. MATERIAL AND METHODS: Two hundred eighty eight consecutively patients aged >60 years who were admitted with sepsis during a two-year-period were retrospectively included in the study. Clinical and laboratory parameters at presentation were analyzed. Causes of sepsis and biochemical markers were compared between the healthcare facility-naïve and the healthcare facility-exposed groups. The effect of comorbidities and previous exposure to the healthcare system on clinical course and outcome of the patients was analyzed. RESULTS: Among the comorbidities that were recorded and included in the analysis, the presence of chronic and acute renal impairment and neurologic disabilities were associated with a worse outcome of sepsis in the elderly. In the same cohort, a previous contact with the healthcare system was found to affect the duration of hospital stay, but not the outcome per se. Sepsis-related markers, such as inflammatory markers were not found to be associated with clinical progression and outcome. CONCLUSIONS: Timely diagnosis and accurate evaluation of the severity of sepsis is required to ensure a better outcome for the patients. Sensitive markers and accurate prognostic models are constantly pursued. The impact of living characteristics of the modern aging society is additionally addressed and their effect on sepsis outcome assessed. Hippokratia 2016, 20(4): 274-278.

14.
Antimicrob Agents Chemother ; 59(12): 7367-73, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26369979

RESUMO

Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidemia/tratamento farmacológico , Janus Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Sepse/tratamento farmacológico , Animais , Antifúngicos/administração & dosagem , Candida albicans/isolamento & purificação , Candidemia/mortalidade , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Camundongos Endogâmicos , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Sepse/mortalidade
15.
Antimicrob Agents Chemother ; 59(2): 782-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403672

RESUMO

The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Ácido Desoxicólico/administração & dosagem , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Hospitais , Humanos , Lactente , Recém-Nascido
16.
Clin Microbiol Infect ; 20(12): 1254-64, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25274142

RESUMO

Current knowledge on the human pathophysiology of fungal infections highlights the crucial role of genetic pitfalls in specific immunity pathways that determine, together with other risk factors, the predisposition to and clinical outcome of fungal disease. In several studies, associations between gene polymorphisms and genetic errors have been implicated in an immunodeficiency phenotype and an increased incidence of opportunistic fungal diseases. The major challenge is to fully understand the complex interactions between genetic variations and multiple factors, and their relative contributions to the final clinical fungal disease phenotype. The aim of this review is to present updated knowledge on immunity genetics and susceptibility to medically relevant fungal diseases, such as those caused by Candida, Aspergillus, and certain other more rare fungi.


Assuntos
Fungos/imunologia , Predisposição Genética para Doença , Micoses/genética , Micoses/imunologia , Infecções Oportunistas/genética , Infecções Oportunistas/imunologia , Humanos , Polimorfismo Genético
18.
Antimicrob Agents Chemother ; 58(12): 7102-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25224003

RESUMO

Urinary tract infections (UTIs) due to extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P < 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation.


Assuntos
Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Rim/efeitos dos fármacos , Pielonefrite/tratamento farmacológico , beta-Lactamases/genética , Animais , Carga Bacteriana/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Expressão Gênica , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Rim/microbiologia , Rim/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pielonefrite/microbiologia , Pielonefrite/patologia , Resultado do Tratamento , beta-Lactamases/metabolismo
19.
Eur J Clin Microbiol Infect Dis ; 33(12): 2131-40, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24939620

RESUMO

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.


Assuntos
Doenças Ósseas Infecciosas/microbiologia , Fungos Mitospóricos/isolamento & purificação , Micoses/microbiologia , Adolescente , Adulto , Antifúngicos/uso terapêutico , Doenças Ósseas Infecciosas/patologia , Doenças Ósseas Infecciosas/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Micoses/patologia , Micoses/terapia , Adulto Jovem
20.
Clin Microbiol Infect ; 20 Suppl 7: 27-48, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24810152

RESUMO

Solid organ transplant (SOT) recipients have a significant risk of invasive fungal diseases (IFD) caused mainly by Candida spp. and Aspergillus spp. Candida spp. is the most frequent agent of IFD in the transplant recipient. The absence of clinical trials and the epidemiological differences in IFD in different transplant programmes mean that there are no definitive recommendations for the diagnosis, treatment and prevention of IFD in SOT, so most of the evidence must be based on clinical experience.


Assuntos
Candidíase Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , Infecções Oportunistas/epidemiologia , Transplante de Órgãos , Transplantados , Candidíase Invasiva/diagnóstico , Candidíase Invasiva/prevenção & controle , Candidíase Invasiva/terapia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/prevenção & controle , Aspergilose Pulmonar Invasiva/terapia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas/terapia
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