Mônica de Cássia Firmida

Clinical impact of Achromobacter xylosoxidans colonization/infection in patients with cystic fibrosis

The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans.

Low‐level resistance and clonal diversity of Pseudomonas aeruginosa among chronically colonized cystic fibrosis patients

A prospective study was conducted in Brazil to evaluate antimicrobial resistance patterns and molecular epidemiology of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients with chronic lung infection. All isolates were obtained between May 2009 and June 2010 from 75 patients seen in four reference centers in Brazil: HCPA (20 patients) and HEOM (15 patients), located in southern and northeastern Brazil, respectively; IFF (20 patients) and HUPE (20 patients), both in southwestern Brazil. Antimicrobial susceptibility testing, PCR for detection of carpapenemases, and pulsed‐field gel electrophoresis (PFGE) were performed in 274 isolates. A total of 224 PFGE types were identified and no clones were found circulating among the centers or within the same center. Despite the chronic infection, most patients were colonized by intermittent clones. Only three patients (4%) maintained the same clone during the study. The resistance rates were lower than 30% for the majority of antimicrobials tested in all centers and only 17% of isolates were multiresistant. Isolates (n = 54) with reduced susceptibility to imipenem and/or meropenem presented negative results for blaSPM‐1, blaIMP−1, blaVIM, and blaKPCgenes. Our results indicate an unexpected low level of antimicrobial resistance and a high genotypic diversity among P. aeruginosa from Brazilian chronic CF patients.

Brazilian guidelines for the diagnosis and treatment of cystic fibrosis

A fibrose cistica (FC) e uma doenca genetica autossomica recessiva caracterizada pela disfuncao do gene CFTR. Trata-se de uma doenca multissistemica que ocorre mais frequentemente em populacoes descendentes de caucasianos. Nas ultimas decadas, diversos avancos no diagnostico e tratamento da FC mudaram drasticamente o cenario dessa doenca, com aumento expressivo da sobrevida e qualidade de vida. Atualmente, o Brasil dispoe de um programa de ampla cobertura para a triagem neonatal de FC e centros de referencia distribuidos na maior parte desses estados para seguimento dos individuos. Antigamente confinada a faixa etaria pediatrica, tem-se observado um aumento de pacientes adultos com FC tanto pelo maior numero de diagnosticos de formas atipicas, de expressao fenotipica mais leve, assim como pelo aumento da expectativa de vida com os novos tratamentos. Entretanto, ainda se observa uma grande heterogeneidade no acesso aos metodos diagnosticos e terapeuticos para FC entre as diferentes regioes brasileiras. O objetivo dessas diretrizes foi reunir as principais evidencias cientificas que norteiam o manejo desses pacientes. Um grupo de 18 especialistas em FC elaborou 82 perguntas clinicas relevantes que foram divididas em cinco categorias: caracteristicas de um centro de referencia; diagnostico; tratamento da doenca respiratoria; tratamento gastrointestinal e nutricional; e outros aspectos. Diversos profissionais brasileiros atuantes na area da FC foram convidados a responder as perguntas formuladas pelos coordenadores. A literatura disponivel foi pesquisada na base de dados PubMed com palavras-chave, buscando-se as melhores respostas as perguntas dos autores.

Achromobacter xylosoxidans infection in cystic fibrosis siblings with different outcomes: Case reports

Introduction The clinical relevance of Achromobacter xylosoxidans infection in cystic fibrosis (CF) remains controversial. This emerging agent in CF has been associated with increased lung inflammation, more frequent exacerbations and more severe lung disease. We describe a pair of CF siblings chronically colonized by the same multilocus genotype of A. xylosoxidans with different clinical courses, and assess whether this species may have developed any virulence traits and antimicrobial resistance that could have contributed to their singular outcomes. Case presentation Two siblings were positive for the F508del and Y1092X mutations, and were chronically colonized by Pseudomonas aeruginosa and Staphylococcus aureus. The female patient had a more severe CF phenotype and faster clinical deterioration than her brother. Her pulmonary function and computed tomography scan lesions were worse than those of her brother, and both parameters progressively declined. She died at 14 years of age, when he was 18. All isolates of A. xylosoxidans were biofilm producers. Achromobacter xylosoxidans showed less swarming motility in the female patient. Conclusions Biofilm production and diminution of motility allow persistence. Only swarming motility differed between the isolates recovered from the two siblings, but this finding is not sufficient to explain the different clinical outcomes despite their similar genotypes. Modifier genes, unknown environmental factors and female gender can partially explain differences between these siblings. We were unable to correlate any microbiological findings with their clinical courses, and more translational studies are necessary to decrease the gap of knowledge between laboratory and clinical data to promote better clinical interventions.

The Role of Multidetector Computed Tomography and the Forced Oscillation Technique in Assessing Lung Damage in Adults With Cystic Fibrosis

BACKGROUND: With increased survival rates and the consequent emergence of an adult population with cystic fibrosis (CF), developing novel tools for periodic evaluations of these patients has become a new challenge. Thus, we sought to determine the contribution of lung-volume quantification using multidetector computed tomography (CT) in adults with CF and to investigate the association between structural changes and functional abnormalities. METHODS: This was a cross-sectional study in which 21 adults with CF and 22 control subjects underwent lung-volume quantification using multidetector CT. Voxel densities were divided into 4 bands: −1,000 to −900 Hounsfield units (HU) (hyperaerated region), −900 to −500 HU (normally aerated region), −500 to −100 HU (poorly aerated region), and −100 to 100 HU (non-aerated region). In addition, all participants performed pulmonary function tests including spirometry, body plethysmography, diffusion capacity for carbon monoxide, and the forced oscillation technique. RESULTS: Adults with CF had more non-aerated regions and poorly aerated regions with lung-volume quantification using multidetector CT than controls. Despite these abnormalities, total lung volume measured by lung-volume quantification using multidetector CT did not differ between subjects and controls. Total lung capacity (TLC) measured by body plethysmography correlated with both total lung volume (rs = 0.71, P < .001) and total air volume (rs = 0.71, P < .001) as measured with lung-volume quantification using multidetector CT. While the hyperaerated regions correlated with the functional markers of gas retention in the lungs (increased residual volume (RV) and RV/TLC ratio), the poorly aerated regions correlated with the resistive parameters measured by the forced oscillation technique (increased intercept resistance and mean resistance). We also observed a correlation between normally aerated regions and highest pulmonary diffusion values (rs = 0.68, P < .001). CONCLUSIONS: In adults with CF, lung-volume quantification using multidetector CT can destimate the lung volumes of compartments with different densities and determine the aerated and non-aerated contents of the lungs; furthermore, lung-volume quantification using multidetector CT is clearly related to pulmonary function parameters.