Genomic Comparative of Pseudomonas aeruginosa Small Colony Variant, Mucoid and Non-mucoid Phenotypes Obtained from a Patient with Cystic Fibrosis During Respiratory Exacerbations.

Pseudomonas aeruginosa, the most prevalent opportunistic pathogen in chronic obstructive pulmonary disease, associated with high morbidity and mortality in patients with cystic fibrosis (CF), is practically impossible to be eradicated from the airways in chronicity. Its extraordinary genomic plasticity is possibly associated with high antimicrobial resistance, virulence factors, and its phenotypic diversity. The occurrence of P. aeruginosa isolates promoting airway infection, showing mucoid, non-mucoid, and small colony variant (SCV) phenotypes, was observed simultaneously, in the present study, in sputum cultures obtained from a male CF young patient with chronic pulmonary infection for over a decade. The isolates belonged to a new ST (2744) were obtained in two moments of exacerbation of the respiratory disease, in which he was hospitalized. Genetic background and phenotypic analysis indicated that the isolates exhibited multi- and pan-antimicrobial resistant profiles, as well as non-susceptible to polymyxin and predominantly hypermutable (HPM) phenotypes. Whole genome sequencing showed variations in genome sizes, coding sequences and their determinants of resistance and virulence. The annotated genomes were compared for antimicrobial resistance, hypermutability, and SCV characteristics. We highlight the lack of reported genetic determinants of SCV emergence and HPM phenotypes, which can be explained in part due to the very short time between collections of isolates. To the best of our knowledge, this is the first report of genome sequencing of P. aeruginosa SCV from a CF patient in Brazil.

Carbapenem-Resistant Pseudomonas aeruginosa in Chronic Lung Infection: Current Resistance Profile and Hypermutability in Patients with Cystic Fibrosis.

Pseudomonas aeruginosa is associated with chronic and progressive lung disease and is closely related to increased morbidity and mortality in cystic fibrosis (CF) patients. Hypermutable (HPM) P. aeruginosa isolates have been described in these patients and are usually associated with antibiotic resistance. This study aimed to investigate the occurrence of carbapenem resistance and hypermutable phenotype in 179 P. aeruginosa isolates from 8 chronically CF patients assisted at two reference centers in Rio de Janeiro, Brazil. Using disk diffusion test, non-susceptible (NS) rates higher than 40% were observed for imipenem, amikacin, and gentamicin. A total of 79 isolates (44.1%), 71 (39.6%), and 8 (4.4%) were classified as carbapenem-resistant (CR resistance to at least one carbapenem), multidrug-resistant (MDR), and extensively drug-resistant (XDR), respectively. Minimal inhibitory concentration was determined for 79 CR P. aeruginosa and showed the following variations: 4 and 128 µg/mL to imipenem, 4 and 64 µg/mL to meropenem, and 4 and ≥ 32 µg/mL to doripenem. We have found only four (2.23%) HPM isolates from 4 patients. Analyzing the genetic relationship among the HPM isolates, 3 pulsed-field gel electrophoresis/pulsotypes (D, M, and J) were observed. Only M pulsotype was recovered from two patients in different years. Polymerase chain reaction screening for blaGES, blaIMP, blaKPC, blaNDM, blaOXA-48, blaSPM, and blaVIM genes was performed for all CR isolates and none of them were positive. Our results demonstrate a high occurrence of CR and MDR P. aeruginosa of CF patients follow-up in both centers studied, while the presence of HPM is still unusual.

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.

Abordagem clínica de lactentes sibilantes / Clinical Approach to Wheezing Infants

O objetivo principal deste artigo foi rever a abordagem clínica de lactentes sibilantes baseada em conhecimentos atuais. Tratou-se de uma revisão não sistemática da literatura através das bases de dados Medline e LILACS. Os artigos foram selecionados de acordo com o tópico de interesse. Lactentes sibilantes são muito comuns na prática clínica. Podem resultar de um sem número de condições clínicas diferentes. Infecções virais são a principal causa nessa faixa etária. Pais usualmente querem saber se seus filhos sofrem de asma e se os sintomas persistirão no futuro. Tais questões não podem ser facilmente respondidas. Foi demonstrado por estudos epidemiológicos retrospectivos que a “sibilância transitória precoce”é o fenótipo mais frequente durante os primeiros anos de vida. No entanto, a utilidade clínica dos fenótipos é limitada. Por outro lado, uma abordagem clínica cuidadosa permite a exclusão de algumas causas específicas de sibilância e pode contribuir para identificar a predisposição para asma, ajudando nas decisões terapêuticas

he main objective of this article was to review the clinical approach to wheezing infants, based on current knowledge.This was a non-systematic review of articles indexed for the Medline and LILACS databases. Only articles dealing with the topic of interest were selected.Wheezing infants are quite common in clinical practice. Such wheezing can result from a number of different conditions, the main cause being viral infections. Parents usually want to know if their kids suffer from asthma and if symptoms will persist into the future. Those questions cannot be easily answered. Retrospective epidemiological studies have shown that “transient early” wheezing is the most common phenotype during the first years of life. However, the utility of phenotypes is limited in clinical settings. Nevertheless, a careful clinical approach allows certain specific causes of wheezing to be excluded and can contribute to identifying a predisposition to asthma, thus facilitating the therapeutic decision-making process.