RESUMO
BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32â mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128â mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32â mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.
Assuntos
Cadaverina/análogos & derivados , Proteínas de Escherichia coli , Escherichia coli , Penicilinas , Escherichia coli/genética , Transporte Biológico , Transativadores , Proteínas de Escherichia coli/genéticaRESUMO
BACKGROUND: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16â mg/L (susceptible with increased exposure) based on a dose of 2â g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates. OBJECTIVES: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae. METHODS: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MICâ≤â16â mg/L) and three as resistant (MICâ>â16â mg/L). The HFIM was performed over 3â days to mimic human-like pharmacokinetics of 2â g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64â mg/L temocillin to detect resistant subpopulations. RESULTS: All isolates showed a reduction in bacterial population of at least 3â log cfu/mL within the first 8â h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values. CONCLUSIONS: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30â min may be inadequate to prevent the emergence of resistant variants.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Penicilinas , Humanos , Antibacterianos/uso terapêutico , Klebsiella pneumoniae , beta-Lactamases/genética , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Proteínas de Bactérias/genéticaRESUMO
BACKGROUND: Nutrition care can positively affect multiple aspects of patient's health; outcomes are commonly evaluated on the basis of their impact on a patient's (i) illness-specific conditions and (ii) health-related quality of life (HRQoL). Our systematic review examined how HRQoL was measured in studies of nutritional interventions. To help future researchers select appropriate Quality of Life Questionnaires (QoLQ), we identified commonly-used instruments and their uses across populations in different regions, of different ages, and with different diseases. METHODS: We searched EMCare, EMBASE, and Medline databases for studies that had HRQoL and nutrition intervention terms in the title, the abstract, or the MeSH term classifications "quality of life" and any of "nutrition therapy", "diet therapy", or "dietary supplements" and identified 1,113 studies for possible inclusion.We then reviewed titles, abstracts, and full texts to identify studies for final inclusion. RESULTS: Our review of titles, abstracts, and full texts resulted in the inclusion of 116 relevant studies in our final analysis. Our review identified 14 general and 25 disease-specific QoLQ. The most-used general QoLQ were the Short-Form 36-Item Health Survey (SF-36) in 27 studies and EuroQol 5-Dimension, (EQ-5D) in 26 studies. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ), a cancer-specific QoLQ, was the most frequently used disease-specific QoLQ (28 studies). Disease-specific QoLQ were also identified for nutrition-related diseases such as diabetes, obesity, and dysphagia. Sixteen studies used multiple QoLQ, of which eight studies included both general and disease-specific measures of HRQoL. The most studied diseases were cancer (36 studies) and malnutrition (24 studies). There were few studies focused on specific age-group populations, with only 38 studies (33%) focused on adults 65 years and older and only 4 studies focused on pediatric patients. Regional variation in QoLQ use was observed, with EQ-5D used more frequently in Europe and SF-36 more commonly used in North America. CONCLUSIONS: Use of QoLQ to measure HRQoL is well established in the literature; both general and disease-specific instruments are now available for use. We advise further studies to examine potential benefits of using both general and disease-specific QoLQ to better understand the impact of nutritional interventions on HRQoL.
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Qualidade de Vida , Humanos , Transtornos de Deglutição , Europa (Continente) , DesnutriçãoRESUMO
Metastasis is the primary cause of death for most breast cancer (BC) patients who succumb to the disease. During the hematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are microenvironmental and systemic processes contributing to cancer regulation. We have recently published that red blood cells (RBCs) that accompany circulating tumor cells have prognostic value in metastatic BC patients. RBC alterations are related to several diseases. Although the principal known role is gas transport, it has been recently assigned additional functions as regulatory cells on circulation. Hence, to explore their potential contribution to tumor progression, we characterized the proteomic composition of RBCs from 53 BC patients from stages I to III and IV, compared with 33 cancer-free controls. In this work, we observed that RBCs from BC patients showed a different proteomic profile compared to cancer-free controls and between different tumor stages. The differential proteins were mainly related to extracellular components, proteasome, and metabolism. Embryonic hemoglobins, not expected in adults' RBCs, were detected in BC patients. Besides, lysosome-associated membrane glycoprotein 2 emerge as a new RBCs marker with diagnostic and prognostic potential for metastatic BC patients. Seemingly, RBCs are acquiring modifications in their proteomic composition that probably represents the systemic cancer disease, conditioned by the tumor microenvironment.
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Neoplasias da Mama , Células Neoplásicas Circulantes , Adulto , Humanos , Feminino , Neoplasias da Mama/metabolismo , Células Neoplásicas Circulantes/metabolismo , Proteômica , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Biomarcadores Tumorais/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Prestação Integrada de Cuidados de Saúde , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Reoperação , Estudos RetrospectivosRESUMO
BACKGROUND: Escherichia coli is the most common cause of bacteremia in high-income countries. To enable the development and implementation of effective prevention strategies, a better understanding of the current epidemiology of invasive E. coli infections is needed. METHODS: A systematic review of literature published between 1 January 2007 and 31 March 2018 on the burden and epidemiology of E. coli bacteremia in populations that include adults in high-income countries was conducted. Meta-analysis was performed for descriptive purposes. RESULTS: During the studied time interval, the estimated incidence rate of E. coli bacteremia was 48 per 100 000 person-years, but this increased considerably with age: rates per 100â 000 person-years wereâ >100 in 55-to-75-year-olds andâ >300 in 75-to-85-year-olds. Overall, E. coli accounted for 27% of documented bacteremia episodes: 18% if hospital acquired, 32% if community-onset healthcare associated, and 33% if community acquired. The estimated case fatality rate was 12%. Approximately 44% of episodes were community acquired, 27% community-onset healthcare associated, and 27% hospital acquired. Urinary tract infection (UTI) was the primary source for 53% of episodes. CONCLUSIONS: This systematic review confirms the substantial burden of E. coli bacteremia in older adults and justifies the implementation of community-level programs to prevent E. coli bacteremia and ideally UTI in this age group.
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Bacteriemia , Infecções Comunitárias Adquiridas , Infecções por Escherichia coli , Infecções Urinárias , Idoso , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Escherichia coli , Infecções por Escherichia coli/epidemiologia , Humanos , Infecções Urinárias/epidemiologiaRESUMO
PURPOSE: Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive ExPEC disease in patients undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), O-serotype distribution and antibiotic resistance profiles of associated E. coli isolates. MATERIALS AND METHODS: Adult men (≥18 years) undergoing TRUS-PNB were enrolled. The TRUS-PNB procedure was performed according to local standard of care, including preferences of prophylactic antibiotics. Clinical and microbiological data were collected. RESULTS: Of the 4,951 patients (mean age 66.9 years) enrolled 4,935 (99.7%) underwent TRUS-PNB (95.1% received prophylactic antibiotics); 98.9% completed the study. Overall incidence of invasive ExPEC disease was 0.67% (33/4,935 patients; 95% CI 0.46-0.94); highest incidence was in the U.S. (0.97%, 14/1,446; 95% CI 0.53-1.62). Prevalence of the 10 selected O-serotypes O1, O2, O4, O6, O8, O15, O16, O18, O25 and O75 was 52.0% (95% CI 31.3-72.2). E. coli isolates showed highest resistance rates to levofloxacin and ciprofloxacin (76%; 95% CI 54.8-90.6 for both). Among fluoroquinolone-resistant ExPEC isolates, prevalence of the 10 selected O-serotypes was 60%. CONCLUSIONS: This study provides an estimate of microbiologically confirmed invasive ExPEC disease incidence following TRUS-PNB. Information on E. coli O-serotype distribution and associated antibiotic resistance profiles from invasive ExPEC disease cases in the first 30 days following TRUS-PNB may help guiding antibiotic use and inform development of a prophylactic ExPEC vaccine.
Assuntos
Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli Extraintestinal Patogênica/isolamento & purificação , Biópsia Guiada por Imagem , Próstata/patologia , Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Idoso , Antibioticoprofilaxia , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Estudos Prospectivos , SorotipagemRESUMO
Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) is a real global health threat. Environmental reservoirs of resistance gene determinats, such as effluents of hospital wastewaters, are acquiring increased relevance in the selection of plasmid-encoded carbapenemase genes. The presence of Hg in environmental reservoirs may exert a positive selective pressure on tolerant bacteria, favoring the co-transfer of carbapenemase genes and mer operons. In our study, 63 CP-Kp isolates were screened for mer operons by whole genome sequencing (MySeq). Conjugation assays were performed with 24 out of 63 CP-Kp isolates harboring the mer operon. Ten transconjugants (Tc-Kp) were selected with Hg. Plasmid DNA of Tc-Kp was extracted and sequenced using single-molecule real-time (SMRT) technology (PacBio, Sequel II system) with later annotation. Plasmid analysis revealed that Tc-Kp from blaIMP-like (n = 3) showed a single plasmid belonging to IncC group with two complete mer operon next to blaIMP-like. Tc-Kp from blaVIM-1 (n = 2) harbored two plasmids, one with blaVIM-1 in an IncL, and mer operon was in an IncFIB plasmid. Tc-Kp from blaOXA-48-like (n = 5) showed 2 plasmids. blaOXA-48-like was found in an IncL plasmid, whereas mer operon was (i) in an IncR plasmid associated with blaCTX-M-15 in 3 Tc-Kp-OXA-48-like, (ii) in an IncC plasmid associated with blaCMY-2 in 1 Tc-Kp-OXA-48-like, (iii) and in an IncFIB plasmid associated with blaCTX-M-15 in 1 Tc-Kp-OXA-48-like. This is, to our knowledge, the first study to describe in K. pneumoniae producing plasmid-encoded carbapenemase, the potential impact of Hg in the co-transfer of mer operons and carbapenemase genes located in the same or different plasmids. KEY POINTS: ⢠Environmental reservoirs are playing an important role in the selection of carbapenemase genes. ⢠Conjugation assays, selecting with Hg, obtained 10 transconjugants with carbapenemase genes. ⢠mer operons were located in the same or different plasmids than carbapenemase genes.
Assuntos
Infecções por Klebsiella , Mercúrio , Proteínas de Bactérias , Células Clonais , Humanos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Óperon , Plasmídeos/genética , beta-Lactamases/genéticaRESUMO
Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and no available molecular targets. CTCs derived xenografts (CDX) have demonstrated to be a promising tool for understanding cancer biology. In our study, a CDX from a TNBC patient was developed for the first time. After CDX characterization, WNT signaling was found as the main mechanism related with this tumor biology and potential CTCs markers were identified and subsequently validated in TNBC patients. In this cohort high levels of MELK expression were associated with poorer survival rates. Overall, our study demonstrates that CTCs from TNBC are tumorigenic and CDXs are a useful model to obtain valuable information about the tumor.
Assuntos
Transplante de Neoplasias , Células Neoplásicas Circulantes/patologia , Transplante Heterólogo , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Animais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Camundongos SCID , Células Tumorais Cultivadas , Via de Sinalização Wnt/fisiologiaRESUMO
The genetic regulation underlying the effect of arsenic (As(III)) on the model symbiosis Medicago-Ensifer was investigated using a combination of physiological (split-roots), microscopy and genetic (microarrays, qRT-PCR and composite plants) tools. Nodulation was very sensitive to As(III) (median inhibitory dose (ID50) = 20 µM). The effect on root elongation and on nodulation was local (nonsystemic). A battery of stress (salt, drought, heat shock, metals, etc.)-related genes were induced. Glutathione played a pivotal role in tolerance/detoxification, together with secondary metabolites ((iso)flavonoids and phenylpropanoids). However, antioxidant enzymes were not activated. Concerning the symbiotic interaction, molecular evidence suggesting that rhizobia alleviate As stress is for the first time provided. Chalcone synthase (which is involved in the first step of the legume-rhizobia cross-talk) was strongly enhanced, suggesting that the plants are biased to establish symbiotic interactions under As(III) stress. In contrast, 13 subsequent nodulation genes (involved in nodulation factors (Nod factors) perception, infection, thread initiation and progression, and nodule morphogenesis) were repressed. Overexpression of the ethylene responsive factor ERN in composite plants reduced root stress and partially restored nodulation, whereas overexpression of the early nodulin ENOD12 enhanced nodulation both in the presence and, particularly, in the absence of As, without affecting root elongation. Several transcription factors were identified, which could be additional targets for genetic engineering aiming to improve nodulation and/or alleviate root stress induced by this toxic.
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Arsênio/toxicidade , Perfilação da Expressão Gênica , Medicago truncatula/genética , Medicago truncatula/microbiologia , Sinorhizobium/fisiologia , Simbiose/genética , Transcriptoma/genética , Arsenitos/toxicidade , Análise por Conglomerados , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Medicago truncatula/efeitos dos fármacos , Medicago truncatula/crescimento & desenvolvimento , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nodulação/efeitos dos fármacos , Nodulação/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Simbiose/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
The usefulness of the standard chemical oxygen demand (COD) test for water characterization is offset to some extent by its requirement for highly toxic or expensive Cr, Ag, and Hg species. In addition, oxidation of the target samples by chromate requires a 2-3 h heating step. We have downscaled this method to obtain a reduction of up to ca. 80% in the use and generation of toxic residues and a time reduction of up to ca. 67%. This also translates into considerable energy savings by reducing the time required for heating as well as costly labour time. Such reductions can be especially important for analytical laboratories with heavy loads of COD analyses. Numerical results obtained with the standard COD method for laboratory KHP samples (potassium hydrogen phthalate) show an average relative error of 1.41% vs. an average of 2.14% obtained with the downsized or small-scale version. The average % standard deviation when using the former is 2.16% vs. 3.24% obtained with the latter. When analysing municipal wastewater samples, the relative error is smaller for the proposed small-scale method than for the standard method (0.05 vs. 0.58, respectively), and the % std. dev. is 1.25% vs. 1.06%. The results obtained with various industrial wastewaters show good agreement with those obtained using the standard method. Chloride ions do not interfere at concentrations below 2000 mg Nacl/L. This highly encouraging proof-of-concept offers a potentially alternative greener approach to COD analysis.
Assuntos
Análise da Demanda Biológica de Oxigênio , Química VerdeRESUMO
During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.
Assuntos
Disruptores Endócrinos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Feminino , Animais , Desenvolvimento Infantil/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Recém-NascidoRESUMO
OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSION: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Neoplasias Hematológicas , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/imunologia , Masculino , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Idoso , Pessoa de Meia-Idade , RNA Viral/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Interferon gama/sangue , Interferon-alfa/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Dexametasona/uso terapêutico , Dexametasona/administração & dosagemRESUMO
OBJECTIVE: Klebsiella oxytoca can cause nosocomial infections, affecting vulnerable newborns. There are few studies describing nosocomial outbreaks in the neonatal intensive care units (NICU). In this study, a systematic review of the literature was carried out to know the main characteristics of these outbreaks and the evolution of one is described. METHODS: We conducted a systematic review in the Medline database up to July 2022, and present a descriptive study of an outbreak with 21 episodes in the NICU of a tertiary hospital, between September 2021 and January 2022. RESULTS: 9 articles met the inclusion criteria. The duration of outbreaks was found to be variable, of which 4 (44.4%) lasted for a year or more. Colonization (69%) was more frequent than infections (31%) and the mortality rate was 22.4%. In studies describing sources, the most frequent was the environmental origin (57.1%). In our outbreak there were 15 colonizations and 6 infections. The infections were mild conjunctivitis without sequelae. Molecular typing analysis made it possible to detect 4 different clusters. CONCLUSIONS: There is an important variability in the evolution and results of the published outbreaks, highlighting a greater number of colonized, use of PFGE (pulsed-field gel electrophoresis) techniques for molecular typing and implementation of control measures. Finally, we describe an outbreak in which 21 neonates were affected with mild infections, resolved without sequelae and whose control measures were effective.
RESUMO
In 2014-2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, four hospitals submitted twenty-nine VIM-1- and CTX-M-15-producing K. pneumoniae ST15 isolates to our laboratory. Seven representatives of each XbaI PFGE pulsotype were sequenced using short- and long-read technologies. RAST, CGE databases, and Pathogenwatch were used for resistance determinants and capsule-type analysis. Plasmid comparison was performed with Easyfig2.1. Phylogenetic analysis included other contemporary ST15 isolates from Spain. The 29 isolates were clustered into seven different pulsotypes. The selected genomes, from three hospitals in two different provinces, were clustered together (fewer than 35 alleles) and differed by more than 100 alleles from other ST15 isolates obtained in the region. These seven isolates harbored one IncR plasmid (200-220 kb) with a common backbone and four regions flanked by IS26: one contained blaVIM-1, another contained blaCTX-M-15, the third contained blaOXA-1, and the fourth harbored heavy-metal-tolerance genes. The two initial plasmids, from two different centers, were identical, and rearrangement of four regions was observed in the five subsequent plasmids. Our findings showed the first intercenter dissemination of IncR plasmids carrying blaVIM-1, blaCTX-M-15, and metal-tolerance genes mediated by a new lineage of K. pneumoniae ST15. Two different capture events of the blaVIM-1 gene or different IS26-mediated plasmid rearrangements from a common ancestor may explain plasmid variations.
RESUMO
OBJECTIVES: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined. METHODS: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected. Whole-genome sequencing was used to characterise the resistome; multi-locus sequence typing was used to investigate phylogeny. RESULTS: Among the 199 cases of documented bacteraemia, 40 (20%) and 20 (10%) were caused by MDR Klebsiella pneumoniae and Enterobacter hormaechei, respectively. Of these, 23 (38.5%) were early neonatal infections (≤3 days of life). Twelve different sequence types (STs) were observed among K. pneumoniae isolates, the most prevalent being ST1805 (n = 10) and ST307 (n = 8). Twenty-one K. pneumoniae isolates (53%) possessed the blaCTX-M-15 gene, six of which co-produced OXA-48; two, NDM-7; and two, OXA-48 and NDM-7. The blaOXA-48 gene was present in 11 K. pneumoniae isolates (27.5%); blaNDM-1, in 13 (32.5%); and blaNDM-7, in 4 (10.0%). Eighteen E. hormaechei isolates (90.0%) produced an extended-spectrum ß-lactamase (ESBL). Three were SHV-12 producers that co-produced CMY-4 and NDM-1, and 15 were CTXM-15 producers, of which 6 co-produced OXA-48. Twelve different STs belonging to three different E. hormaechei subspecies were observed, with one to four isolates. K. pneumoniae and E. hormaechei isolates belonging to the same ST had less than 20 single nucleotide polymorphism differences and were found throughout the study period, highlighting their endemic presence in the neonatal intensive care unit. CONCLUSION: Thirty percent of neonatal sepsis cases (23 early and 37 late) were caused by highly drug-resistant carbapenemase- and/or ESBL-producing Enterobacterales.
Assuntos
Bacteriemia , Infecções por Klebsiella , Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Unidades de Terapia Intensiva Neonatal , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Tipagem de Sequências Multilocus , Sepse Neonatal/epidemiologia , Sepse Neonatal/tratamento farmacológico , Marrocos/epidemiologia , beta-Lactamases/genética , Klebsiella pneumoniae/genética , Sepse/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológicoRESUMO
This study evaluated the usefulness of the three-dimensional representation of electrocardiogram traces (3DECG) to reveal acute and gradual changes during a full session of hemodiafiltration (HDF) in end-stage renal disease (ESRD) patients. Fifteen ESRD patients were included (six men, nine women, age 46 ± 19 years old). Serum electrolytes, blood pressure, heart rate, and blood urea nitrogen (BUN) were measured before and after HDF. Continuous electrocardiograms (ECGs) obtained by Holter monitoring during HDF were used to produce the 3DECG. Several major disturbances were identified by 3DECG images: increase in QRS amplitude (47%), decrease in T-wave amplitude (33%), increase in heart rate (33%), and occurrence of arrhythmia (53%). Different arrhythmia types were often concurrent and included isolated supraventricular premature beats (N = 5), atrial fibrillation or atrial bigeminy (N = 2), and isolated premature ventricular beats (N = 6). Patients with decrease in T-wave amplitude had higher potassium and BUN (both before HDF and total removal) than those without decrease in T-wave amplitude (P < 0.05). Concurrent acute and gradual ECG changes during HDF are identified by the 3DECG, which could be useful as a preventive and prognostic method.