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2.
BMJ Med ; 3(1): e000731, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184567

RESUMEN

Objectives: To describe the effect of multimorbidity on adverse patient centred outcomes in people attending emergency department. Design: Population based cohort study. Setting: Emergency departments in NHS Lothian in Scotland, from 1 January 2012 to 31 December 2019. Participants: Adults (≥18 years) attending emergency departments. Data sources: Linked data from emergency departments, hospital discharges, and cancer registries, and national mortality data. Main outcome measures: Multimorbidity was defined as at least two conditions from the Elixhauser comorbidity index. Multivariable logistic or linear regression was used to assess associations of multimorbidity with 30 day mortality (primary outcome), hospital admission, reattendance at the emergency department within seven days, and time spent in emergency department (secondary outcomes). Primary analysis was stratified by age (<65 v ≥65 years). Results: 451 291 people had 1 273 937 attendances to emergency departments during the study period. 43 504 (9.6%) had multimorbidity, and people with multimorbidity were older (median 73 v 43 years), more likely to arrive by emergency ambulance (57.8% v 23.7%), and more likely to be triaged as very urgent (23.5% v 9.2%) than people who do not have multimorbidity. After adjusting for other prognostic covariates, multimorbidity, compared with no multimorbidity, was associated with higher 30 day mortality (8.2% v 1.2%, adjusted odds ratio 1.81 (95% confidence interval (CI) 1.72 to 1.91)), higher rate of hospital admission (60.1% v 20.5%, 1.81 (1.76 to 1.86)), higher reattendance to an emergency department within seven days (7.8% v 3.5%, 1.41 (1.32 to 1.50)), and longer time spent in the department (adjusted coefficient 0.27 h (95% CI 0.26 to 0.27)). The size of associations between multimorbidity and all outcomes were larger in younger patients: for example, the adjusted odds ratio of 30 day mortality was 3.03 (95% CI 2.68 to 3.42) in people younger than 65 years versus 1.61 (95% CI 1.53 to 1.71) in those 65 years or older. Conclusions: Almost one in ten patients presenting to emergency department had multimorbidity using Elixhauser index conditions. Multimorbidity was strongly associated with adverse outcomes and these associations were stronger in younger people. The increasing prevalence of multimorbidity in the population is likely to exacerbate strain on emergency departments unless practice and policy evolve to meet the growing demand.

3.
J Aquat Anim Health ; 36(3): 275-280, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39150020

RESUMEN

OBJECTIVE: A female Rio Cauca caecilian Typhlonectes natans (estimated as between 10 and 18 years of age) housed at the Smithsonian National Zoological Park in Washington, D.C., developed progressive severe coelomic effusion over a 4-week period. The coelomic effusion was diagnosed via radiographs and ultrasound, and a sample of the fluid was obtained for analysis, which revealed a low-protein transudate suggestive of inflammation. As the coelomic effusion progressed, the caecilian became tachypneic, hyporexic, and lethargic. The caecilian was started on antibiotics and a diet trial, but signs continued despite therapy. METHODS: An exploratory celiotomy was performed, which revealed adipose tissue torsion with local lymphangiectasia and a presumptive biliary cyst. Surgical correction was unable to be achieved due to concern for fatal hemorrhage, as the vasculature associated with the torsion was severely distended. Due to the severity of the torsion and associated risks, the caecilian was euthanized intraoperatively and subsequently necropsied for histologic evaluation. RESULT: After reviewing the caecilian's presentation and the progression of disease, it is suspected that the severe coelomic effusion was secondary to lymphangiectasia, which occurred subsequent to the adipose tissue torsion. CONCLUSION: This is the first reported case of adipose tissue torsion and associated clinical disease in an aquatic caecilian and should be a differential for progressive coelomic effusion in this species.


Asunto(s)
Tejido Adiposo , Animales , Femenino , Tejido Adiposo/patología , Anomalía Torsional/veterinaria , Anomalía Torsional/cirugía , Anomalía Torsional/patología , Linfedema/veterinaria , Linfedema/patología , Animales de Zoológico
4.
ISME J ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39030691

RESUMEN

Arthropods, such as houseflies, play a significant role on the dissemination of antimicrobial resistance (AMR); however, their impact has often been overlooked in comparison to other AMR vectors. Understanding the contribution of arthropods to the spread of AMR is critical for implementing robust policies to mitigate the spread of AMR across "One Health" sectors. Herein, we investigated the in-situ transfer of a gfp-labelled AMR plasmid (IncA/C carrying a mcr-8 gene, pA/C_MCR-8) in the gut microbiota of housefly (Musca domestica) by applying single-cell sorting, 16S rRNA gene amplicon sequencing, and whole genome sequencing. Our findings demonstrate that the pA/C_MCR-8 positive E. coli donor strain is capable of colonizing the gut microbiome of houseflies and persists in the housefly intestine for five days, however, no transfer was detectable above the detection threshold of 10-5 per cell. The conjugative plasmid, pA/C_MCR-8 demonstrated a high transfer frequency ranging from 4.1 × 10-3 to 5.0 × 10-3 per cell in vitro, and exhibited transfer across various bacterial phyla, primarily encompassing Pseudomonadota and Bacillota. Phylogenic analysis has revealed that Providencia stuartii, a human opportunistic pathogen, was a notable recipient of pA/C_MCR-8. The conjugation assays further revealed that newly formed P. stuartii transconjugants readily transfer pA/C_MCR-8 to other clinically relevant pathogens (e.g. Klebsiella pneumoniae). Our findings indicate the potential transfer of AMR plasmids from houseflies to human opportunistic pathogens and further advocates the adoption of a One Health approach in developing infection control policies that address AMR across clinical settings.

5.
Intensive Care Med ; 50(6): 890-900, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38844640

RESUMEN

PURPOSE: Factors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not. METHODS: This is a cohort study including all women delivering in Scottish hospitals between 01/01/2005 and 31/12/2018, using national healthcare databases. The primary exposure was intensive care unit (ICU) admission, while secondary exposures included high dependency unit admission. Outcomes included hospital readmission (1-year post-hospital discharge, 1-year mortality, psychiatric hospital admission, stillbirth, and neonatal critical care admission). Multivariable Cox and logistic regression were used to report hazard ratios (HR) and odds ratios (OR) of association between ICU admission and outcomes. RESULTS: Of 762,918 deliveries, 1449 (0.18%) women were admitted to ICU, most commonly due to post-partum hemorrhage (225, 15.5%) followed by eclampsia/pre-eclampsia (133, 9.2%). Over-half (53.8%) required mechanical ventilation. One-year hospital readmission was more frequent in women admitted to ICU compared with non-ICU populations [24.5% (n = 299) vs 8.9% (n = 68,029)]. This association persisted after confounder adjustment (HR 1.93, 95% confidence interval [CI] 1.33, 2.81, p < 0.001). Furthermore, maternal ICU admission was associated with increased 1-year mortality (HR 40.06, 95% CI 24.04, 66.76, p < 0.001), stillbirth (OR 12.31, 95% CI 7.95,19.08, p < 0.001) and neonatal critical care admission (OR 6.99, 95% CI 5.64,8.67, p < 0.001) after confounder adjustment. CONCLUSION: Critical care admission increases the risk of adverse short-term and long-term maternal, pregnancy and neonatal outcomes. Optimizing long-term post-partum care may benefit maternal critical illness survivors.


Asunto(s)
Readmisión del Paciente , Humanos , Femenino , Embarazo , Adulto , Readmisión del Paciente/estadística & datos numéricos , Cuidados Críticos/estadística & datos numéricos , Cuidados Críticos/métodos , Estudios de Cohortes , Unidades de Cuidados Intensivos/estadística & datos numéricos , Escocia/epidemiología , Resultado del Embarazo/epidemiología , Recién Nacido , Enfermedad Crítica/mortalidad , Complicaciones del Embarazo/epidemiología , Mortalidad Materna/tendencias , Admisión del Paciente/estadística & datos numéricos
6.
N Engl J Med ; 391(8): 722-735, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38869931

RESUMEN

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).


Asunto(s)
Anemia , Lesiones Traumáticas del Encéfalo , Transfusión de Eritrocitos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anemia/sangre , Anemia/etiología , Anemia/terapia , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Enfermedad Crítica , Depresión/etiología , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Escala de Consecuencias de Glasgow , Hemoglobinas/análisis , Calidad de Vida
7.
Nat Commun ; 15(1): 5498, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38944647

RESUMEN

IncX3 plasmids carrying the New Delhi metallo-ß-lactamase-encoding gene, blaNDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying blaNDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying blaNDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary ß-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the blaNDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of blaNDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of blaNDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds.


Asunto(s)
Antibacterianos , Pollos , Conjugación Genética , Escherichia coli , Plásmidos , beta-Lactamasas , Animales , Plásmidos/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Pollos/microbiología , Humanos , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Sistemas de Secreción Tipo IV/genética , Sistemas de Secreción Tipo IV/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Amoxicilina/farmacología , Regiones Promotoras Genéticas/genética , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/transmisión , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Intestinos/microbiología
8.
Chem Sci ; 15(25): 9620-9629, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38939155

RESUMEN

Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant S. aureus; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in S. aureus. This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development.

10.
Heliyon ; 10(7): e28052, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596009

RESUMEN

Background: Carbapenem resistance is epidemic worldwide, these last resort antimicrobials are listed in the WHO 'watch group' with higher resistance potential. During the years 2017-18 Pakistan Antimicrobial Resistance Surveillance System reported an increase in carbapenem resistance. However, a comprehensive information on prevalence and molecular epidemiology of carbapenem resistance in Pakistan is not available. This systematic review and meta-analysis is aimed to report the current carbapenem resistance situation in Pakistan and its treatment options. Methods: In this systematic review and meta-analysis, we investigated the pooled prevalence (PPr) of carbapenem resistance in Enterobacteriaceae and non-Enterobacteriaceae by organizing available data, from Web of Science and PubMed by April 2, 2020, in various groups and subgroups including species, years, provinces, extended spectrum ß-lactamase production, clinical presentation, carbapenemase and metallo-ß-lactamase production, and New Delhi metallo-ß-lactamase (NDM) prevalence. Literature review was updated for the studies publisehd by December 07, 2023. Moreover, we descriptively reviewed the molecular epidemiology of carbapenem resistance in Enterobacteriaceae and non-Enterobacteriaceae in Pakistan. Lastly, we statistically explored different treatment options available for carbapenem resistant infections. We used R package 'metafor' for performing meta-analysis and influence diagnostics and determining treatment options. Results: From two academic databases Web of Science and PubMed we identified 343 studies. Eighty-eight studies were selected for the systematic review and meta-analysis. Seventy-four studies were selected for phenotypic analysis, 36 for genotypic analysis, and 31 for available treatment options. PPr-ID of 12% [0.12 (0.07, 0.16)] was observed for phenotypic carbapenem resistance in Enterobacteriaceae with more prevalence recorded in Klebsiella pneumoniae 24% [0.24 (0.05, 0.44)] followed by 9% [0.09 (-0.03, 0.20)] in Escherichia coli. During the last two decades we observed a striking increase in carbapenem resistance PPr i.e., from 0% [0.00 (-0.02, 0.03)] to 36% [0.36 (0.17, 0.56)]. blaNDM with PPr 15% [0.15 (0.06, 0.23)] in naive isolates was found to be the fundamental genetic determinant for carbapenem resistance in Enterobacteriaceae in Pakistan. Polymyxin B, colistin, tigecycline, and fosfomycin were identified as the suggested treatment options available for multidrug resistant infections not responding to carbapenems. Various studies reported carbapenem resistance from human, animal, and environment sources. Conclusion: In conclusion, we found that NDM-1 producing carbapenem resistant Enterobacteriaceae are increasing in Pakistan. Meta-analysis showed that metallo-ß-lactamases producing E. coli ST405 and K. pneumoniae sequence type11 are the major resistant clones. Number of reported studies in various subgroups and inconsistency in following CLSI guidelines are the potential limitations of this meta-analysis. A National antimicrobial resistance (AMR) surveillance strategy based on One Health is urgently needed to check any future AMR crisis in Pakistan.

11.
Emerg Microbes Infect ; 13(1): 2337678, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38629492

RESUMEN

Despite carbapenems not being used in animals, carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-ß-lactamase-producing CRE (NDM-CRE), are prevalent in livestock. Concurrently, the incidence of human infections caused by NDM-CRE is rising, particularly in children. Although a positive association between livestock production and human NDM-CRE infections at the national level was identified, the evidence of direct transmission of NDM originating from livestock to humans remains largely unknown. Here, we conducted a cross-sectional study in Chengdu, Sichuan Province, to examine the prevalence of NDM-CRE in chickens and pigs along the breeding-slaughtering-retail chains, in pork in cafeterias of schools, and in colonizations and infections from children's hospital and examined the correlation of NDM-CRE among animals, foods and humans. Overall, the blaNDM increases gradually along the chicken and pig breeding (4.70%/2.0%) -slaughtering (7.60%/22.40%) -retail (65.56%/34.26%) chains. The slaughterhouse has become a hotspot for cross-contamination and amplifier of blaNDM. Notably, 63.11% of pork from the school cafeteria was positive for blaNDM. The prevalence of blaNDM in intestinal and infection samples from children's hospitals was 21.68% and 19.80%, respectively. whole genome sequencing (WGS) analysis revealed the sporadic, not large-scale, clonal spread of NDM-CRE along the chicken and pig breeding-slaughtering-retail chain, with further spreading via IncX3-blaNDM plasmid within each stage of whole chains. Clonal transmission of NDM-CRE is predominant in children's hospitals. The IncX3-blaNDM plasmid was highly prevalent among animals and humans and accounted for 57.7% of Escherichia coli and 91.3% of Klebsiella pneumoniae. Attention should be directed towards the IncX3 plasmid to control the transmission of blaNDM between animals and humans.


Asunto(s)
Infecciones por Enterobacteriaceae , Enterobacteriaceae , Niño , Humanos , Animales , Porcinos , Enterobacteriaceae/genética , Estudios Transversales , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Pollos , Escherichia coli/genética , beta-Lactamasas/genética , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/veterinaria , Klebsiella pneumoniae/genética , Plásmidos
12.
BMJ Open ; 14(4): e081637, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580355

RESUMEN

INTRODUCTION: An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. METHODS AND ANALYSIS: This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. ETHICS AND DISSEMINATION: All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. TRIAL REGISTRATION NUMBER: NCT03653832.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Enfermedad Crítica , Humanos , Enfermedad Crítica/terapia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Unidades de Cuidados Intensivos , Cuidados Críticos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Nat Commun ; 15(1): 3654, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688912

RESUMEN

The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens. However, knowledge remain limited about the contribution made by environmental stress on the evolution of bacterial AMR by modulating horizontal acquisition of AMR plasmids and other mobile genetic elements. Here we combined experimental evolution, whole genome sequencing, reverse genetic engineering, and transcriptomics to examine if the evolution of chromosomal AMR to triclosan (TCS) disinfectant has correlated effects on modulating bacterial pathogen (Klebsiella pneumoniae) permissiveness to AMR plasmids and phage susceptibility. Herein, we show that TCS exposure increases the evolvability of K. pneumoniae to evolve TCS-resistant mutants (TRMs) by acquiring mutations and altered expression of several genes previously associated with TCS and antibiotic resistance. Notably, nsrR deletion increases conjugation permissiveness of K. pneumoniae to four AMR plasmids, and enhances susceptibility to various Klebsiella-specific phages through the downregulation of several bacterial defense systems and changes in membrane potential with altered reactive oxygen species response. Our findings suggest that unrestricted use of TCS disinfectant imposes a dual impact on bacterial antibiotic resistance by augmenting both chromosomally and horizontally acquired AMR mechanisms.


Asunto(s)
Bacteriófagos , Klebsiella pneumoniae , Plásmidos , Triclosán , Triclosán/farmacología , Plásmidos/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/virología , Bacteriófagos/genética , Bacteriófagos/fisiología , Farmacorresistencia Bacteriana Múltiple/genética , Mutación , Transferencia de Gen Horizontal , Secuenciación Completa del Genoma , Evolución Molecular , Antibacterianos/farmacología
15.
Nat Commun ; 15(1): 2758, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553439

RESUMEN

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.


Asunto(s)
Países en Desarrollo , Sepsis Neonatal , Recién Nacido , Humanos , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Hospitales , Antibacterianos/farmacología , Klebsiella pneumoniae/genética , Bacterias Gramnegativas/genética , Pruebas de Sensibilidad Microbiana
17.
ACS Appl Mater Interfaces ; 16(3): 4117-4125, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38194473

RESUMEN

3D integration of multiple microelectronic devices improves size, weight, and power while increasing the number of interconnections between components. One integration method involves the use of metal bump bonds to connect devices and components on a common interposer platform. Significant variations in the coefficient of thermal expansion in such systems lead to stresses that can cause thermomechanical and electrical failures. More advanced characterization and failure analysis techniques are necessary to assess the bond quality between components. Frequency domain thermoreflectance (FDTR) is a nondestructive, noncontact testing method used to determine thermal properties in a sample by fitting the phase lag between an applied heat flux and the surface temperature response. The typical use of FDTR data involves fitting for thermal properties in geometries with a high degree of symmetry. In this work, finite element method simulations are performed using high performance computing codes to facilitate the modeling of samples with arbitrary geometric complexity. A gradient-based optimization technique is also presented to determine unknown thermal properties in a discretized domain. Using experimental FDTR data from a GaN-diamond sample, thermal conductivity is then determined in an unknown layer to provide a spatial map of bond quality at various points in the sample.

18.
Lancet Microbe ; 5(1): e13-e23, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38006896

RESUMEN

BACKGROUND: The global spread of plasmid-borne carbapenem resistance is an ongoing public health challenge; however, the nature of such horizontal gene transfer events among complex bacterial communities remains poorly understood. We examined the in-situ transfer of the globally dominant New Delhi metallo-ß-lactamase (NDM)-5-positive IncX3 plasmid (denoted pX3_NDM-5) in hospital wastewater to simulate a real-world, One Health antimicrobial resistance context. METHODS: For this transmission study, we tagged pX3_NDM-5 with the green fluorescent protein gene, gfp, using a CRISPR-based method and transferred the plasmid to a donor Escherichia coli strain. Bacteria were extracted from a hospital wastewater treatment plant (Fujian Provincial Maternity and Children's Hospital, Fuzhou, China) as the bacterial recipient community. We mixed this recipient community with the E coli donor strain carrying the gfp-tagged plasmid, both with and without sodium hypochlorite (NaClO) as an environmental stressor, and conducted several culture-based and culture-independent conjugation assays. The conjugation events were observed microscopically and quantified by fluorescence-activated cell sorting. We analysed the taxonomic composition of the sorted transconjugal pool by 16S rRNA gene amplicon sequencing and assessed the stability of the plasmid in the isolated transconjugants and its ability to transfer back to E coli. FINDINGS: We show that the plasmid pX3_NDM-5 has a broad host range and can transfer across various bacterial phyla, including between Gram-negative and Gram-positive bacteria. Although environmental stress with NaClO did not affect the overall plasmid transfer frequency, it reduced the breadth of the transconjugant pool. The taxonomic composition of the transconjugal pool was distinct from that of the recipient communities, and environmental stress modulated the permissiveness of some operational taxonomic units towards the acquisition of pX3_NDM-5. Notably, pX3_NDM-5 transconjugants included the Gram-positive pathogen Enterococcus faecalis, and the plasmid could subsequently be reconjugated back to E coli. These findings suggest that E faecalis could act as a natural shuttle vector for the wide dissemination of pX3_NDM-5 plasmids. INTERPRETATION: Our culture-independent conjugation model simulates natural environmental conditions and challenges the established theory that Gram-negative and Gram-positive bacteria rarely exchange clinically important plasmids. The data show that plasmids disseminate more widely across genera and phyla than previously thought. These findings have substantial implications when considering the spread of antimicrobial resistance across One Health sectors. FUNDING: The Laboratory of Lingnan Modern Agriculture Project, the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province of China, and the Outstanding Young Research Talents Program of Fujian Agriculture and Forestry University.


Asunto(s)
Antiinfecciosos , Escherichia coli , Femenino , Embarazo , Niño , Humanos , Escherichia coli/genética , Aguas Residuales , ARN Ribosómico 16S/genética , Plásmidos/genética , Bacterias/genética , Hospitales
19.
Infect Control Hosp Epidemiol ; 45(4): 501-508, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38017626

RESUMEN

OBJECTIVE: To determine the effectiveness of dry hydrogen peroxide (DHP) in reducing environmental bioburden in occupied areas. DESIGN: Prospective environmental cohort study. SETTING: The study was conducted in 2 tertiary-care hospitals and 1 free-standing emergency department. INTERVENTION: Environmental air and surface sites were cultured before and after continuous deployment of DHP systems in targeted hospital areas. METHODS: In total, 1,554 surface and 1,036 air samples were collected from 74 patient areas among the 3 facilities on 3 consecutive days before DHP deployment and on days 14, 30, 60, and 90 after deployment. At each sampling time, 2 air samples were collected at each facility from 1 room without DHP, along with 2 outdoor samples from each facility. The impact of negative-pressure usage on the efficacy of DHP was also evaluated, with 1 hospital continuously using negative pressure, another utilizing it only in patient isolation scenarios, and another without negative pressure. RESULTS: In the 2 facilities without continuous negative pressure, exposure to DHP was associated with a significant reduction in surface bioburden, characterized as total colony-forming units (P = .019; P = .002). Significant associations between DHP exposure and reductions in airborne bacterial load at the 2 hospitals were observed (P ≤ .001; P = .041), and the free-standing emergency department experienced a reduction that did not achieve statistical significance (P = .073). CONCLUSIONS: Our findings confirm that DHP has the potential to reduce microbial air and surface bioburden in occupied patient rooms with standard ventilation parameters.


Asunto(s)
Peróxido de Hidrógeno , Aislamiento de Pacientes , Humanos , Estudios Prospectivos , Estudios de Cohortes , Hospitales
20.
Trends Microbiol ; 32(4): 365-378, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38008597

RESUMEN

Colistin is regarded as a last-line drug against serious infections caused by multidrug-resistant Gram-negative bacterial pathogens. Therefore, the emergence of mobile colistin resistance (mcr) genes has attracted global concern and led to policy changes for the use of colistin in food animals across many countries. Currently, the distribution, function, mechanism of action, transmission vehicles, origin of mcr, and new treatment strategies against MCR-producing pathogens have been extensively studied. Here we review the prevalence, structure and function of mcr, the fitness cost and persistence of mcr-carrying plasmids, the impact of MCR on host immune response, as well as the control strategies to combat mcr-mediated colistin resistance.


Asunto(s)
Colistina , Proteínas de Escherichia coli , Animales , Colistina/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Plásmidos/genética , Farmacorresistencia Bacteriana Múltiple/genética , Proteínas de Escherichia coli/genética , Pruebas de Sensibilidad Microbiana
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