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1.
Clin Immunol ; 263: 110202, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575045

RESUMO

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

2.
JAC Antimicrob Resist ; 6(2): dlae031, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38449517

RESUMO

Background: Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures. Objectives: We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population. Methods: We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort. Results: We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality. Conclusions: PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.

3.
J Am Med Dir Assoc ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320741

RESUMO

OBJECTIVE: In July 2021, as part of a planned multiyear broad and long-term organizational realignment, the general medicine service assumed continuous care of residents at a Community Living Center (CLC), which are nursing homes within the Veterans Affairs (VA) health care system. We hypothesized that practitioners accustomed to caring for patients in acute care would be more likely to prescribe antibiotics to long-term care residents. DESIGN: Retrospective cohort study. SETTINGS AND PARTICIPANTS: Residents of a 105-bed CLC associated with a large VA medical center. METHODS: Our cohort included CLC residents between July 1, 2020, and June 30, 2022. We used administrative data to assess resident demographics and medical conditions in the 1 year before and after the change of practitioners. We also compared antibiotics agents prescribed and the following antibiotic use metrics in the year before and after the change: days of therapy (DOT) per 1000 bed days of care (BDOC), antibiotic starts/1000 BDOC, and mean length of therapy in days. RESULTS: Resident characteristics and overall antibiotic use metrics were similar before and after the change in staffing. The specific agents prescribed differed, with a decrease in fluoroquinolones (14.3 to 5.8 DOT/1000 BDOC; P < .01) and an increase doxycycline (7.4 vs 19.1 DOT/1000 BDOC; P < .01) after the staff change. Rates of Clostridioides difficile infection also decreased, from 6.23 to 3.41 cases/10,000 BDOC after the change in staffing. CONCLUSIONS AND IMPLICATIONS: The comparable antibiotic use metrics before and after the general medical service assumed care of the CLC residents may be explained by constancy in resident population and other facility-related factors. Differences in the types of agents used suggests that antibiotic stewardship efforts can be tailored not only to the setting and patient population but also to the practitioners' discipline.

5.
Public Health Nutr ; 27(1): e35, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224091

RESUMO

OBJECTIVE: The present study examined the association of BMI, fat mass, physical activity engagement (PA), maximal oxygen consumption (VO2max), screen time and academic performance (AP) with Mediterranean diet (MD) adherence in a sample of high socio-economic status (SES) children. DESIGN: A non-randomised design was used. A multilinear regression model was developed using backward elimination. Analysis included variables pertaining to age, BMI, VO2max, fat percentage, AP, PA engagement and screen time. All participants had a high SES and so this variable was not included as a predictor. Data met the assumptions required for multiple regressions in terms of linearity, homoscedasticity, normality, independence and non-multicollinearity. SETTING: Two state and three mixed funding schools in Granada, Spain. PARTICIPANTS: Data were collected from 244 children aged between 10 and 12 years. RESULTS: Better AP, higher PA engagement and lower screen time were found to be predictive of MD adherence. These variables explained 22·9 % of the variance in data measuring adolescent MD adherence. CONCLUSIONS: The present study suggests that, in addition to SES, PA, AP and screen time are important components to consider when targeting improvements in MD adherence in children. It is, therefore, concluded that interventions targeting improvements in PA, AP and screen time are needed to promote MD adherence in children, regardless of SES.


Assuntos
Dieta Mediterrânea , Criança , Adolescente , Humanos , Espanha , Status Econômico , Inquéritos e Questionários , Estudos Transversais
6.
Clin Child Psychol Psychiatry ; 29(1): 245-258, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37909657

RESUMO

INTRODUCTION: Resilience and quality of life (QOL) can involve a positive approach in group interventions for parents of children with autism spectrum disorders (ASD). This study aims to evaluate resilience and family QOL at the start of a psychoeducational group. METHODS: Cross-sectional assessment of resilience and family QOL used the Family Quality of Life Scale (ECVF) and 14-item Resilience Scale (RS-14). RESULTS: The study group showed high levels of resilience. Parents considered the resources/support domain crucial, although satisfaction in this area was comparatively lower. Concerns about low satisfaction with available resources and support were notable. Gender differences were observed but not statistically significant. DISCUSSION: The study's findings support prior research on parental resilience in families of children with ASD. The literature on the QOL for these families presents mixed findings. The importance of parental involvement in service planning is highlighted. CONCLUSIONS: This study emphasizes the importance of resilience in parents of children with ASD, suggesting it as a potential therapeutic target. The findings underscore the need to address the perceived low quality of available resources and support. Further investigation is needed.


Assuntos
Transtorno do Espectro Autista , Resiliência Psicológica , Criança , Humanos , Transtorno do Espectro Autista/terapia , Qualidade de Vida , Estudos Transversais , Pais
7.
Artigo em Inglês | MEDLINE | ID: mdl-38156202

RESUMO

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment. Results: A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality. Conclusions: Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy.

8.
Children (Basel) ; 10(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38002861

RESUMO

(1) Background: The present study aimed to examine the relationship between physical activity (PA), screen time (ST), maximal oxygen uptake (VO2max), Mediterranean diet (MD) adherence, self-esteem (SE) and academic performance (AP) in primary education students. In order to address this aim, an explanatory model was developed to examine the existing relationships between PA, ST, VO2max, MD adherence, SE and AP. Further, the proposed structural model was examined via multi-group analysis as a function of sex and school type. (2) Methods: A non-experimental, descriptive, comparative and cross-sectional study was designed with a total sample of 269 Spanish students (11.29 ± 0.62). Validated questionnaires were administered to collect data on study variables. (3) Results: Relative to boys, girls reported better academic grades and showed a stronger positive relationship between MD adherence and AP, MD adherence and PA, and VO2max and SE. Likewise, girls showed a stronger negative relationship between ST and VO2max, and ST and MD adherence. At the same time, mixed funding school (MFS) students reported higher PA engagement than state school (SS) students. However, SS students reported better MD adherence, ST and AP than MFS students. Further, a stronger positive relationship was found in SS students between MD adherence or VO2max and SE than in MFS students. Also, within the former group, ST was more negatively related to MD adherence and VO2max. (4) Conclusions: Scientific and educational communities must develop future strategies that consider potential determinants in order to target more desirable outcomes.

9.
Clin Exp Immunol ; 214(3): 328-340, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37455655

RESUMO

Usually, the massive elimination of cells under steady-state conditions occurs by apoptosis, which is also acknowledged to explain the loss of enterocytes in the small intestine of celiac disease (CD) patients. However, little is known about the role of proinflammatory cell death pathways in CD. Here, we have used confocal microscopy, western blot, and RT-qPCR analysis to assess the presence of regulated cell death pathways in the duodenum of CD patients. We found an increased number of dead (TUNEL+) cells in the lamina propria of small intestine of CD patients, most of them are plasma cells (CD138+). Many dying cells expressed FAS and were in close contact with CD3+ T cells. Caspase-8 and caspase-3 expression was increased in CD, confirming the activation of apoptosis. In parallel, caspase-1, IL-1ß, and GSDMD were increased in CD samples indicating the presence of inflammasome-dependent pyroptosis. Necroptosis was also present, as shown by the increase of RIPK3 and phosphorylate MLKL. Analysis of published databases confirmed that CD has an increased expression of regulated cell death -related genes. Together, these results reveal that CD is characterized by cell death of different kinds. In particular, the presence of proinflammatory cell death pathways may contribute to mucosal damage.


Assuntos
Doença Celíaca , Piroptose , Humanos , Piroptose/genética , Necroptose/genética , Apoptose/genética , Morte Celular
10.
Materials (Basel) ; 16(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37176434

RESUMO

Research on the use of biomass resources for the generation of energy and chemical compounds is of great interest worldwide. The development and growth of the biodiesel industry has led to a parallel market for the supply of glycerol, its main by-product. Its wide availability and relatively low cost as a raw material make glycerol a basic component for obtaining various chemical products and allows for the development of a biorefinery around biodiesel plants, through the technological integration of different production processes. This work proposes a review of one of the reactions of interest in the biorefinery environment: the hydrogenolysis of glycerol to 1,2-propylene glycol. The article reviews more than 300 references, covering literature from about 20 years, focusing on the heterogeneous catalysts used for the production of glycol. In this sense, from about 175 catalysts, between bulk and supported ones, were revised and discussed critically, based on noble metals, such as Ru, Pt, Pd, and non-noble metals as Cu, Ni, Co, both in liquid (2-10 MPa, 120-260 °C) and vapor phase (0.1 MPa, 200-300 °C). Then, the effect of the main operational and decision variables, such as temperature, pressure, catalyst/glycerol mass ratio, space velocity, and H2 flow, are discussed, depending on the reactors employed. Finally, the formulation of several kinetic models and stability studies are presented, discussing the main deactivation mechanisms of the catalytic systems such as coking, leaching, and sintering, and the presence of impurities in the glycerol feed. It is expected that this work will serve as a tool for the development of more efficient catalytic materials and processes towards the future projection of glycerol biorefineries.

11.
Infect Control Hosp Epidemiol ; 44(9): 1518-1521, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36762817

RESUMO

For primary care clinics at a Veterans' Affairs (VA) medical center, the shift from in-person to telehealth visits during the coronavirus disease 2019 (COVID-19) pandemic was associated with low rates of antibiotic prescription. Understanding contextual factors associated with antibiotic prescription practices during telehealth visits may help promote antibiotic stewardship in primary care settings.


Assuntos
COVID-19 , Telemedicina , Humanos , Pandemias , Antibacterianos/uso terapêutico
12.
J Am Med Dir Assoc ; 24(1): 22-26.e1, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36462546

RESUMO

OBJECTIVES: COVID-19 disproportionately affected nursing home residents and people from racial and ethnic minorities in the United States. Nursing homes in the Veterans Affairs (VA) system, termed Community Living Centers (CLCs), belong to a national managed care system. In the period prior to the availability of vaccines, we examined whether residents from racial and ethnic minorities experienced disparities in COVID-19 related mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents at 134 VA CLCs from April 14 to December 10, 2020. METHODS: We used the VA Corporate Data Warehouse to identify VA CLC residents with a positive SARS-CoV-2 polymerase chain reaction test during or 2 days prior to their admission and without a prior case of COVID-19. We assessed age, self-reported race/ethnicity, frailty, chronic medical conditions, Charlson comorbidity index, the annual quarter of the infection, and all-cause 30-day mortality. We estimated odds ratios and 95% confidence intervals of all-cause 30-day mortality using a mixed-effects multivariable logistic regression model. RESULTS: During the study period, 1133 CLC residents had an index positive SARS-CoV-2 test. Mortality at 30 days was 23% for White non-Hispanic residents, 15% for Black non-Hispanic residents, 10% for Hispanic residents, and 16% for other residents. Factors associated with increased 30-day mortality were age ≥70 years, Charlson comorbidity index ≥6, and a positive SARS-CoV-2 test between April 14 and June 30, 2020. Frailty, Black race, and Hispanic ethnicity were not independently associated with an increased risk of 30-day mortality. CONCLUSIONS AND IMPLICATIONS: Among a national cohort of VA CLC residents with COVID-19, neither Black race nor Hispanic ethnicity had a negative impact on survival. Further research is needed to determine factors within the VA health care system that mitigate the influence of systemic racism on COVID-19 outcomes in US nursing homes.


Assuntos
COVID-19 , Fragilidade , Veteranos , Humanos , Estados Unidos/epidemiologia , Idoso , Etnicidade , SARS-CoV-2 , Estudos Retrospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-36483389

RESUMO

In this large, retrospective cohort study, we used administrative data to evaluate nonpregnant adults with group B Streptococcus (GBS) bacteriuria. We found greater all-cause mortality in those with urinary tract infections compared to asymptomatic bacteriuria. Differences in patients' baseline characteristics and the 1-year mortality rate raise the possibility that provider practices contribute to differences observed.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36554716

RESUMO

Psychomotor skills are, among others, an aspect particularly valuable for structuring the teaching-learning process of infant schoolchildren. For this reason, a study was carried out with the aim of describing and comparing the socio-demographic, psychomotor, and learning levels of schoolchildren in the second stage of infant education. Ninety-five pupils from the second cycle of infant education in the capital of Granada took part in this study. A sociodemographic questionnaire, the movement assessment battery for children-2 (MABC-2), and the preschool learning behaviour scale (PLBS) were used to collect data. The main results show that manual dexterity appears as the main motor factor and similar figures in the three dimensions of learning behaviours. On the other hand, balance and learning behaviours were higher in 6-year-old schoolchildren. In terms of gender, girls obtained higher values for the level of the learning behaviour variables. A positive correlation was found between the dimensions of learning and motor activity.


Assuntos
Aprendizagem , Destreza Motora , Criança , Lactente , Feminino , Humanos , Pré-Escolar , Movimento , Extremidade Superior , Instituições Acadêmicas
15.
Artigo em Inglês | MEDLINE | ID: mdl-36310777

RESUMO

Objectives: To assess the prevalence of antibiotic-resistant gram-negative bacteria (R-GNB) among patients without recent hospitalization and to examine the influence of outpatient antibiotic exposure on the risk of acquiring R-GNB in this population. Design: 2-year retrospective cohort study. Setting: Regional Veterans Affairs healthcare system. Patients: Outpatients at 13 community-based clinics. Methods: We examined the rate of acquisition of R-GNB within 90 days following an outpatient visit from 2018 to 2019. We used clinical and administrative databases to determine and summarize prescriptions for systemic antibiotics, associated infectious diagnoses, and subsequent R-GNB acquisition among patients without recent hospitalizations. We also calculated the odds ratio of R-GNB acquisition following antibiotic exposure. Results: During the 2-year study period, 7,215 patients had outpatient visits with microbiological cultures obtained within 90 days. Of these patients, 206 (2.9%) acquired an R-GNB. Among patients receiving antibiotics at the visit, 4.6% acquired a R-GNB compared to 2.7% among patients who did not receive antibiotics, yielding an unadjusted odds ratio of 1.75 (95% confidence interval, 1.18-2.52) for a R-GNB following an outpatient visit with versus without an antibiotic exposure. Regardless of R-GNB occurrence, >50% of antibiotic prescriptions were issued at visits without an infectious disease diagnosis or issued without documentation of an in-person or telehealth clinical encounter. Conclusions: Although the rate of R-GNBs was low (2.9%), the 1.75-fold increased odds of acquiring a R-GNB following an outpatient antibiotic highlights the importance of antimicrobial stewardship efforts in outpatient settings. Specific opportunities include reducing antibiotics prescribed without an infectious diagnosis or a clinical visit.

16.
Immunol Lett ; 251-252: 56-62, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36309159

RESUMO

The intestinal mucosa is covered by a layer of epithelial cells that is constantly challenged by commensal, opportunistic, and pathogenic microorganisms, their components, and harmful compounds. Any inflammatory response to these materials must be tightly controlled to limit tissue damage and restore the integrity of the mucosal barrier. We have shown previously that production of IL-1ß via activation of the inflammasome can lead to mucosal damage in the small intestinal pathology that occurs after intragastric administration of a gluten derived peptide, p31-43. Here we show that specific inhibition of caspase-1 or NLRP3 abolishes the damage induced by p31-43, and that antibody-mediated blocking of IL-1ß inhibits the both the histological changes and the induction of apoptosis and caspase-3 activation driven by p31-43. Understanding the role of IL-1ß in sterile inflammation may help to understand chronic inflammatory pathological processes, and design new intervention strategies.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Caspase 1/metabolismo , Inflamação/patologia , Intestino Delgado/patologia , Apoptose
17.
mBio ; 13(3): e0033622, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35548953

RESUMO

Carbapenem and multidrug-resistant (MDR) Acinetobacter baumannii leads the World Health Organization's list of priority pathogens and represents an unmet medical need. Understanding the mechanisms underpinning the acquisition of antibiotic resistance in this pathogen is fundamental to the development of novel therapeutics as well as to infection prevention and antibiotic stewardship strategies designed to limit its spread. In their investigation, "Interbacterial Transfer of Carbapenem Resistance and Large Antibiotic Resistance Islands by Natural Transformation in Pathogenic Acinetobacter," Anne-Sophie Godeux and colleagues (mBio 13:e0263121, 2022, https://doi.org/10.1128/mBio.02631-21) delineate the unsuspected extent and circumstances under which natural transformation as a mechanism of intraspecies and interspecies exchange of genetic material occurs in Acinetobacter spp. This study offers key insights into how this notorious pathogen may have accelerated the development of its MDR phenotype via an unexpectedly robust and unnervingly casual approach to the acquisition of antibiotic resistance determinants through natural transformation.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Carbapenêmicos , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana
18.
Sportis (A Coruña) ; 8(2): 239-254, May. 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-207470

RESUMO

The motivation developed towards sport plays a key role in the adherence to a healthy dietary pattern, however, it also plays an important role towards digital entertainment. Taking this into account, the present study aims to develop an explanatory model of the incidence of sport motivation on adherence to a healthy dietary pattern and adherence to video games and to contrast the structural model by means of a multi-group analysis according to gender. To this end, a cross-sectional descriptive comparative study was carried out with 1112 participants (25.09±6.22). The instruments used were a sociodemographic questionnaire, the Predimed questionnaire, the Perceived Motivational Climate in Sport Questionnaire (PMCSQ-2) and the Video Game Related Experiences Questionnaire (CERV). Finally, the results reveal that the female sex obtains a negative relationship between sport motivation and digital leisure, while the male sex reflects a negative relationship between task climate and adherence to the Mediterranean diet. (AU)


La motivación desarrollada hacia el deporte juega un papel clave en la adherencia a un patrón dietético saludable, sin embargo, también juega un papel importante hacia el ocio digital. El presente estudio pretende desarrollar un modelo explicativo de la incidencia de la motivación hacia el deporte en la adherencia a un patrón dietético saludable y la adicción a los videojuegos y contrastar el modelo estructural mediante un análisis multigrupo en función del sexo de los participantes. Para ello se realizó un estudio descriptivo comparativo transversal con 1112 participantes (25,09±6,22). Los instrumentos utilizados fueron un cuestionario sociodemográfico, el cuestionario Predimed, el Cuestionario de Clima Motivacional Percibido en el Deporte (PMCSQ-2) y el Cuestionario de Experiencias Relacionadas con los Videojuegos (CERV). Finalmente, los resultados revelan que el sexo femenino obtiene una relación negativa entre la motivación deportiva y el ocio digital, mientras que el sexo masculino refleja una relación negativa entre el clima de tarea y la adherencia a la dieta mediterránea. (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Motivação , Educação Física e Treinamento , Atividade Motora , Dieta , Atividades de Lazer , Sexo , Epidemiologia Descritiva , Inquéritos e Questionários , Estudos Transversais
19.
PLoS One ; 17(3): e0265129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358221

RESUMO

BACKGROUND: Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time. METHODS: Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the study period, antimicrobial susceptibility testing, whole genome sequencing (WGS), phylogenetic analyses and RNAseq were performed in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time. RESULTS: The majority of isolates were resistant to almost all tested antibiotics. A phylogenetic reconstruction revealed 3 major clades representing a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggested that a group of closely related strains was present in the patient prior to transplantation and continued to change throughout the course of treatment. A trend toward accumulation of mutations over time was observed. Different mutations in the DNA mismatch repair gene mutL consistent with a hypermutator phenotype were observed in two clades. RNAseq performed on 12 representative isolates revealed substantial differences in the expression of genes associated with antibiotic resistance and virulence traits. CONCLUSIONS: The overwhelming current practice in the clinical laboratories setting relies on obtaining a pure culture and reporting the antibiogram from a few isolated colonies to inform therapy decisions. Our analyses revealed significant underlying genomic heterogeneity and unpredictable evolutionary patterns that were independent of prior antibiotic treatment, highlighting the need for comprehensive sampling and population-level analysis when gathering microbiological data in the context of CF P. aeruginosa chronic infection. Our findings challenge the applicability of antimicrobial stewardship programs based on single-isolate resistance profiles for the selection of antibiotic regimens in chronic infections such as CF.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa
20.
BMC Infect Dis ; 22(1): 237, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260097

RESUMO

BACKGROUND: Population-based surveillance studies may underestimate osteomyelitis caused by Group B Streptococcus (GBS). We analyzed cases of GBS osteomyelitis, including patients diagnosed using an expanded case definition that incorporates cultures from non-sterile sites, as well as cultures from normally sterile sites. METHODS: We retrospectively examined a cohort of veterans with the diagnosis of osteomyelitis between 2008 and 2017. Cases of definite GBS osteomyelitis required GBS isolation from normally sterile sites, (e.g., blood or bone). Cases of probable GBS osteomyelitis permitted GBS isolation from non-sterile sites (e.g., surgical sites, wounds). We compared comorbid conditions, lower extremity amputation and mortality rates in these groups. RESULTS: Among 1281 cases of GBS osteomyelitis, the median age was 63 years, 87% had diabetes mellitus and 37% had peripheral vascular disease. Similar characteristics were found in 768 (60%) cases classified as definite and 513 (40%) classified as probable GBS osteomyelitis. Polymicrobial infection was less frequent in patients with definite than with probable GBS osteomyelitis (45% vs. 85%; P < 0.001). Mortality rates within 1-year were similar for definite and probable GBS osteomyelitis (12% vs. 10%). Amputation within 1-year occurred in 21% of those with definite and 10% of those with probable GBS osteomyelitis of the lower extremity, with comparable rates in the subset with monomicrobial infection. CONCLUSIONS: Expanding the definition of GBS osteomyelitis to include cases with cultures from non-sterile sites may be warranted, increasing the estimated burden of GBS osteomyelitis. This can help guide preventive efforts to reduce the impact of GBS osteomyelitis.


Assuntos
Osteomielite , Infecções Estreptocócicas , Humanos , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Osteomielite/epidemiologia , Estudos Retrospectivos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae , Estados Unidos/epidemiologia , Saúde dos Veteranos
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