Virulence factors in carbapenem-resistant hypervirulent Klebsiella pneumoniae

Hypervirulence and carbapenem-resistant have emerged as two distinct evolutionary pathotypes of Klebsiella pneumoniae, with both reaching their epidemic success and posing a great threat to public health. However, as the boundaries separating these two pathotypes fade, we assist a worrisome convergence in certain high-risk clones, causing hospital outbreaks and challenging every therapeutic option available. To better understand the basic biology of these pathogens, this review aimed to describe the virulence factors and their distribution worldwide among carbapenem-resistant highly virulent or hypervirulent K. pneumoniae strains, as well as to understand the interplay of these virulence strains with the carbapenemase produced and the sequence type of such strains. As we witness a shift in healthcare settings where carbapenem-resistant highly virulent or hypervirulent K. pneumoniae are beginning to emerge and replace classical K. pneumoniae strains, a better understanding of these strains is urgently needed for immediate and appropriate response

From Inception to Implementation: Strategies for Setting Up Pulmonary Telerehabilitation

BackgroundThe emergence of innovative technology-enabled models of care is an opportunity to support more efficient ways of organizing and delivering healthcare services and improve the patient experience. Pulmonary telerehabilitation started as a promising area of research and became a strategic pandemic response to patients' decreased accessibility to rehabilitation care. Still, in the pre-COVID-19 era, we conducted a participatory study aiming to develop strategies for setting up pulmonary telerehabilitation as a person-centered digitally-enabled model of care.MethodsWe performed operational participatory research between June 2019 and March 2020 with the engagement of all stakeholders involved in the implementation of pulmonary telerehabilitation, including 14 people with Chronic Obstructive Pulmonary Disease. Patients were assessed subjectively and objectively pre and post a 3-month pulmonary rehabilitation program including exercise and education, which started in a face-to-face hospital setting during the first month and continued as a home-based, remotely supervised exercise training intervention.ResultsFive major groups of requirements targeted operational strategies for setting up pulmonary telerehabilitation: (1) pulmonary rehabilitation core principles, (2) quality and security standards, (3) technological functionality, (4) home environment appropriateness, and (5) telesetting skills. There was a statistical significance in the median change in the CAT score from 15.5 to 10.5 (p = 0.004) and in the PRAISE score from 49.5 to 53.0 (p = 0.006). Patients' mean levels of satisfaction regarding rehabilitation goals achievements were 88.1 ± 8.6% and the mean levels of satisfaction regarding the telerehabilitation experienced as a model of care were 95.4% ± 6.3%.ConclusionsThe success of telerehabilitation implementation was grounded on stakeholder engagement and targeted strategies for specific setup requirements, achieving patients' high satisfaction levels. Such operational experiences should be integrated into the redesigning of upgraded telerehabilitation programs as part of the solution to improve the effectiveness, accessibility, and resilience of health systems worldwide

Bacteriémias : determinantes genéticos de resistência e virulência em isolados clínicos de Escherichia coli e Klebsiella spp

Tese de mestrado, Microbiologia Clínica, Faculdade de Medicina, Universidade de Lisboa, 2009O isolamento de Escherichia coli e Klebsiella spp. multirresistentes produtores de ß-lactamases de espectro alargado (ESBL) em infecções invasivas severas como as bacteriémias, constitui um grande desafio terapêutico. De modo a aumentar o conhecimento destes microorganismos, efectuou-se a caracterização dos determinantes genéticos de resistência e virulência de isolados obtidos ao longo de 7 anos (2000-2007) no Hospital de Santa Maria. A Klebsiella spp. demonstrou uma grande variabilidade genotípica, contrastando com a existência de um clone predominante nos isolados de E. coli, o qual persiste em diferentes serviços do hospital há 5 anos. Este clone é produtor da ESBL CTX-M15 e pertence maioritariamente ao grupo filogenético B2, embora esteja também presente em isolados do grupo D, A e B1. A superior capacidade de disseminação horizontal da E. coli comparativamente à Klebsiella spp. (2,04 replicões/isolado Vs 0,59 replicões/isolado), aliado à especificidade plasmídica encontrada (grupo IncF Vs grupo HI1 e P) sugere que os genes contidos nestes elementos genéticos móveis não são facilmente transmitidos entres estas espécies. O clone descrito apresenta as ilhas de patogenicidade IV536, ICFT073 e IICFT073 e os padrões de virulência com apenas dois (fimH, ecpA) ou três (fimH, ecpA,iucC) dos nove factores pesquisados. Até à data apenas descrita na E. coli entero-hemorrágica O157:H7 78, o factor de aderência EcpA surge no presente trabalho sempre associada à fímbria FimH. Estudos adicionais são requeridos, no entanto parece existir uma acção combinada entre ambos: a FimH permite a adesão e invasão no epitélio vesical ou no enterócito actuando como causa primária da bacteriémia, enquanto que a EcpA possibilita a fuga ao sistema imunitário e, consequentemente a sua persistência no hospedeiro.The isolation of Escherichia coli e Klebsiella spp multidrud-producing ESBL in severe invasiveinfections such as bacteraemia, is a major therapeutic challenge. To increase knowledge of these microorganisms, it was made the characterization of the genetic determinants of resistance and virulence of isolates obtained over 7 years (2000-2007) at Hospital de Santa Maria. The Klebsiella spp. has demonstrated a great genetic variability, in contrast with the existence of a predominant clone in the isolates of E. coli, which persists in different departments of the hospital for 5 years. This clone is a ESBL CTX-M15 producer and belong mostly to phylogenetic group B2, but is also present in isolates of group D, A and B1. The superior ability of horizontal spread of E. coli compared with Klebsiella spp. (2.04 replicons/isolate Vs 0.59 replicons/isolate) as well as the specific plasmid group found (group IncF Vs HI1 and P group) suggests that genes contained in these mobile genetic elements are not easily transferred between these species. The clone described presents the pathogenicity islands IV536, ICFT073 and IICFT073 and the virulence patterns mostly found the presence of only two (fimH, ecpA) or three (fimH, ecpA, iucC) of the nine virulence factors investigated. So far only described in entero-haemorrhagic E.coli O157:H7 78, the EcpA pilus-adherence factor appears in this work always associated with the fimbriae FimH. Additional studies are required, however there appears to be a combined action between them: the fimH allows adhesion and invasion in the bladder epithelium or in the enterocyte acting as a primary cause of bacteremia, while the EcpA allows the "escape" of the immune system and consequently its persistence in the host

Design of pulmonary rehabilitation programmes during acute exacerbations of COPD: a systematic review and network meta-analysis

This systematic review aimed to systematise the different designs used to deliver pulmonary rehabilitation during acute exacerbations of COPD (AECOPD) and explore which ones are the most effective. PubMed, Scopus, Web of Science, EBSCO and Cochrane were searched. Randomised controlled trials comparing pulmonary rehabilitation or at least one of its components with usual care or comparing different components of pulmonary rehabilitation were included. Network meta-analysis was conducted in MetaXL 5.3 using a generalised pairwise modelling framework. Pooled effects compared each treatment to usual care. 42 studies were included. Most studies were conducted in an inpatient setting (57%) and started the intervention 24-48 h after hospital admission (24%). Exercise training (71%), education and psychosocial support (57%) and breathing techniques (55%) were the most used components. Studies combining exercise with breathing techniques presented the larger effects on exercise capacity (weighted mean difference (WMD) -41.06, 95% CI -131.70-49.58) and health-related quality of life (WMD 16.07, 95% CI 10.29-21.84), and breathing techniques presented the larger effects on dyspnoea (WMD 1.90, 95% CI 0.53-3.27) and length of hospitalisation (effect size =0.15, 95% CI -0.28-0.57). A few minor adverse events were found.Pulmonary rehabilitation is a safe intervention during AECOPD. Exercise, breathing techniques, and education and psychosocial support seem to be the core components for implementing pulmonary rehabilitation during AECOPD. Studies may now focus on comparisons of optimal timings to start the intervention, total duration of the intervention, duration and frequency of sessions, and intensity for exercise prescription.publishe

Validity and reliability of a new incremental step test for people with chronic obstructive pulmonary disease

Incremental step tests (IST) can be used to assess exercise capacity in people with chronic obstructive pulmonary disease (COPD). The development of a new step test based on the characteristics of the incremental shuttle walk test (ISWT) is an important study to explore. We aimed to develop a new IST based on the ISWT in people with COPD, and assess its validity (construct validity) and reliability, according to Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) recommendations. A cross-sectional study was conducted in participants recruited from hospitals/clinics. During the recruitment, the participants who presented a 6-minute walk test (6MWT) report in the previous month were also identified and the respective data was collected. Subsequently, participants attended two sessions at their homes. IST was conducted on the first visit, along with the 1 min sit-to-stand (1MSTS) test. IST was repeated on a second visit, performed 5–7 days after the first one. Spearman’s correlations were used for construct validity, by comparing the IST with the 6MWT and the 1MSTS. Intraclass correlation coefficient (ICC2,1), SE of measurement (SEM) and minimal detectable change at 95% CI (MDC95) were used for reliability. The learning effect was explored with the Wilcoxon signed-rank test. 50 participants (70.8±7.5 years) were enrolled. IST was significant and moderate correlated with the 6MWT (ρ=0.50, p=0.020), and with the 1MSTS (ρ=0.46, p=0.001). IST presented an ICC2,1=0.96, SEM=10.1 (16.6%) and MDC95=27.9 (45.8%) for the number of steps. There was a statistically significant difference between the two attempts of the IST (p=0.030). Despite the significant and moderate correlations with the 6MWT and 1MSTS, the inability to full compliance with the COSMIN recommendations does not yet allow the IST to be considered valid in people with COPD. On the other hand, the IST is a reliable test based on its high ICC, but a learning effect and an ‘indeterminate’ measurement error were shown.info:eu-repo/semantics/publishedVersio

Effects of a home-based pulmonary rehabilitation program in patients with chronic obstructive pulmonary disease in GOLD B group : a pilot study

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Patients with chronic obstructive pulmonary disease (COPD) in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) B group can be included in pulmonary rehabilitation (PR) settings outside the hospitals. This study aimed to explore the feasibility of a home-based pulmonary rehabilitation (HBPR) program and assess its impact on patients with COPD in the GOLD B group. A real-world, pre-post intervention study was conducted with 12 weeks of HBPR (presential home visits and phone calls) using the self-management program Living Well with COPD. The 1-min sit-to-stand test (1MSTS), modified Medical Research Council Questionnaire (mMRC), COPD Assessment Test (CAT), Hospital Anxiety and Depression Scale (HADS), and London Chest Activity of Daily Living (LCADL) were used to assess the impact. Pre-post differences and correlations between changes in outcomes were calculated. In 30 patients (71.6 years, FEV1 (%) 52.8), significant improvements (p < 0.05) were observed on 1MSTS (Pre 17.2, Post 21.2), mMRC (Pre 2.0, Post 1.0), CAT (Pre 16.3, Post 9.9), HADS (Pre 14.4, Post 9.6), and LCADL (Pre 21.0, Post 15.8), with no adverse events reported. When significant, correlations between changes in outcomes were moderate or strong (0.48 ≤ ρ ≤ 0.66). HBPR can be feasible and safe, and it shows the potential to significantly improve outcomes of patients with COPD in the GOLD B group.info:eu-repo/semantics/publishedVersio

Adapted chester step test can have maximal response characteristics for the assessment of exercise capacity in young women

Chester step test (CST) estimates the exercise capacity through a submaximal response, which can limit its application in the prescription of exercise. This study aimed to assess whether an adaptation of the CST (with a progressive profile) can have maximal response characteristics in young women and compare it to the incremental shuttle walk test (ISWT). Another aim was to determine its within-day test–retest reliability. A cross-sectional study was conducted with 25 women (20.3 ± 1.5 years) who performed the field tests twice on two different days (48 h apart).info:eu-repo/semantics/publishedVersio

Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal – A cross-sectional and retrospective observational study

IntroductionExtensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center.MethodsAll XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed.ResultsOne hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p &lt; 0.05), followed by the ones with bacteremia (44.4%, p &lt; 0.05) and those medicated with colistin (39.0%, p &lt; 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower.DiscussionXDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors’ knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal

Enhance access to pulmonary rehabilitation with a structured and personalized home-based program—reabilitAR: protocol for real-world setting

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Home-based models represent one of the solutions to respond to the poor accessibility of pulmonary rehabilitation (PR) services in patients with chronic respiratory disease (CRD). The main goal of this protocol is to present the implementation of the first nationwide home-based PR program—reabilitAR—in Portugal and the strategies to assess its benefits in patients with CRD. The program consists of 2 phases: a 12-week intensive phase and a 40-week maintenance phase (total: 52 weeks, 1 year). The intervention in both phases is composed of presential home visits and phone-call follow ups, including exercise training and the self-management educational program Living Well with COPD. Dyspnea, impact of the disease, emotional status, and level of dyspnea during activities of daily living are used as patient-reported outcomes measures. A one-minute sit-to-stand test is used as a functional outcome, and the number of steps as a measure of physical activity. To ensure safety, fall risk and the cognitive function are assessed. Data are collected at baseline, at 12 weeks, at 26 weeks and at 52 weeks. This is the first nationwide protocol on enhancing access to PR, providing appropriate responses to CRD patients’ needs through a structured and personalized home-based program in Portugal.info:eu-repo/semantics/publishedVersio

Genomic epidemiological analysis of Klebsiella pneumoniae from Portuguese hospitals reveals insights into circulating antimicrobial resistance.

Klebsiella pneumoniae (Kp) bacteria are an increasing threat to public health and represent one of the most concerning pathogens involved in life-threatening infections and antimicrobial resistance (AMR). To understand the epidemiology of AMR of Kp in Portugal, we analysed whole genome sequencing, susceptibility testing and other meta data on 509 isolates collected nationwide from 16 hospitals and environmental settings between years 1980 and 2019. Predominant sequence types (STs) included ST15 (n = 161, 32%), ST147 (n = 36, 7%), ST14 (n = 26, 5%) or ST13 (n = 26, 5%), while 31% of isolates belonged to STs with fewer than 10 isolates. AMR testing revealed widespread resistance to aminoglycosides, fluoroquinolones, cephalosporins and carbapenems. The most common carbapenemase gene was blaKPC-3. Whilst the distribution of AMR linked plasmids appears uncorrelated with ST, their frequency has changed over time. Before year 2010, the dominant plasmid group was associated with the extended spectrum beta-lactamase gene blaCTX-M-15, but this group appears to have been displaced by another carrying the blaKPC-3 gene. Co-carriage of blaCTX-M and blaKPC-3 was uncommon. Our results from the largest genomics study of Kp in Portugal highlight the active transmission of strains with AMR genes and provide a baseline set of variants for future resistance monitoring and epidemiological studies