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1.
Annu Rev Biochem ; 86: 567-583, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28654325

RESUMO

Multidrug resistance is a global threat as the clinically available potent antibiotic drugs are becoming exceedingly scarce. For example, increasing drug resistance among gram-positive bacteria is responsible for approximately one-third of nosocomial infections. As ribosomes are a major target for these drugs, they may serve as suitable objects for novel development of next-generation antibiotics. Three-dimensional structures of ribosomal particles from Staphylococcus aureus obtained by X-ray crystallography have shed light on fine details of drug binding sites and have revealed unique structural motifs specific for this pathogenic strain, which may be used for the design of novel degradable pathogen-specific, and hence, environmentally friendly drugs.


Assuntos
Antibacterianos/síntese química , Proteínas de Bactérias/química , Desenho de Fármacos , Ribossomos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Cristalografia por Raios X , Deinococcus/efeitos dos fármacos , Deinococcus/genética , Deinococcus/metabolismo , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Modelos Moleculares , Ribossomos/metabolismo , Ribossomos/ultraestrutura , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Thermus thermophilus/efeitos dos fármacos , Thermus thermophilus/genética , Thermus thermophilus/metabolismo
2.
Cell ; 169(5): 849-861.e13, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28502769

RESUMO

We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.


Assuntos
Evolução Biológica , Enterococcus/genética , Animais , Doenças Transmissíveis Emergentes/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Enterococcus/classificação , Enterococcus/citologia , Enterococcus/efeitos dos fármacos , Especiação Genética , Interações Hospedeiro-Patógeno , Larva/microbiologia , Mariposas/crescimento & desenvolvimento , Mariposas/microbiologia , Filogenia , RNA Ribossômico 16S/genética
3.
Nature ; 623(7985): 132-138, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853126

RESUMO

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.


Assuntos
COVID-19 , Infecção Hospitalar , Transmissão de Doença Infecciosa , Pacientes Internados , Pandemias , Humanos , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , COVID-19/transmissão , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Inglaterra/epidemiologia , Hospitais , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Quarentena/estatística & dados numéricos , SARS-CoV-2
4.
CA Cancer J Clin ; 70(6): 480-504, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32910493

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID-19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID-19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio-oncology and outlines key modifications in the approach to this ever-increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS-CoV-2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.


Assuntos
Antineoplásicos/efeitos adversos , COVID-19/complicações , Doenças Cardiovasculares/etiologia , Infecção Hospitalar/prevenção & controle , Neoplasias/complicações , Neoplasias/terapia , Antraciclinas/efeitos adversos , COVID-19/fisiopatologia , COVID-19/prevenção & controle , COVID-19/transmissão , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/terapia , Humanos , Inibidores de Proteassoma/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Radioterapia/efeitos adversos , Receptor ErbB-2/antagonistas & inibidores , Encaminhamento e Consulta , SARS-CoV-2 , Trastuzumab/efeitos adversos
5.
N Engl J Med ; 389(19): 1766-1777, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37815935

RESUMO

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).


Assuntos
Anti-Infecciosos Locais , Infecções Assintomáticas , Clorexidina , Infecção Hospitalar , Casas de Saúde , Povidona-Iodo , Humanos , Administração Cutânea , Administração Intranasal , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Banhos , Clorexidina/administração & dosagem , Clorexidina/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/terapia , Hospitalização/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Povidona-Iodo/administração & dosagem , Povidona-Iodo/uso terapêutico , Higiene da Pele/métodos , Infecções Assintomáticas/terapia
6.
PLoS Pathog ; 20(4): e1012075, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568937

RESUMO

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.


Assuntos
COVID-19 , Infecção Hospitalar , Microbiota , Humanos , SARS-CoV-2/genética , Bactérias , Microbiota/genética
7.
PLoS Genet ; 19(7): e1010646, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37498819

RESUMO

The Gram-negative bacterial pathogen Acinetobacter baumannii is a major cause of hospital-acquired opportunistic infections. The increasing spread of pan-drug resistant strains makes A. baumannii top-ranking among the ESKAPE pathogens for which novel routes of treatment are urgently needed. Comparative genomics approaches have successfully identified genetic changes coinciding with the emergence of pathogenicity in Acinetobacter. Genes that are prevalent both in pathogenic and a-pathogenic Acinetobacter species were not considered ignoring that virulence factors may emerge by the modification of evolutionarily old and widespread proteins. Here, we increased the resolution of comparative genomics analyses to also include lineage-specific changes in protein feature architectures. Using type IVa pili (T4aP) as an example, we show that three pilus components, among them the pilus tip adhesin ComC, vary in their Pfam domain annotation within the genus Acinetobacter. In most pathogenic Acinetobacter isolates, ComC displays a von Willebrand Factor type A domain harboring a finger-like protrusion, and we provide experimental evidence that this finger conveys virulence-related functions in A. baumannii. All three genes are part of an evolutionary cassette, which has been replaced at least twice during A. baumannii diversification. The resulting strain-specific differences in T4aP layout suggests differences in the way how individual strains interact with their host. Our study underpins the hypothesis that A. baumannii uses T4aP for host infection as it was shown previously for other pathogens. It also indicates that many more functional complexes may exist whose precise functions have been adjusted by modifying individual components on the domain level.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecção Hospitalar , Humanos , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Filogenia , Infecção Hospitalar/microbiologia , Infecções por Acinetobacter/microbiologia , Hospitais , Antibacterianos
8.
Clin Microbiol Rev ; 37(2): e0013523, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38421181

RESUMO

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/terapia , Fatores de Risco , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia , Antibacterianos/uso terapêutico , História do Século XXI
9.
N Engl J Med ; 386(24): 2283-2294, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35704480

RESUMO

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).


Assuntos
Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
10.
CA Cancer J Clin ; 68(5): 340-355, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29985544

RESUMO

Therapies in oncology have evolved rapidly over the last years. At the same pace, supportive care for patients receiving cancer therapy has also evolved, allowing patients to safely receive the newest advances in treatment in both an inpatient and outpatient basis. The recognition of the role of infection control and prevention (ICP) in the outcomes of patients living with cancer has been such that it is now a requirement for hospitals and involves multidisciplinary groups. Some unique aspects of ICP for patients with cancer that have gained momentum over the past few decades include catheter-related infections, multidrug-resistant organisms, community-acquired viral infections, and the impact of the health care environment on the horizontal transmission of organisms. Furthermore, as the potential for infections to cross international borders has increased, alertness for outbreaks or new infections that occur outside the area have become constant. As the future approaches, ICP in immunocompromised hosts will continue to integrate emerging disciplines, such as antibiotic stewardship and the microbiome, and new techniques for environmental cleaning and for controlling the spread of infections, such as whole-genome sequencing. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society.


Assuntos
Institutos de Câncer/normas , Hospedeiro Imunocomprometido , Controle de Infecções/métodos , Controle de Infecções/normas , Neoplasias/imunologia , Assistência Ambulatorial/normas , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Gestão de Antimicrobianos , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Dieta , Farmacorresistência Bacteriana Múltipla , Inocuidade dos Alimentos , Desinfecção das Mãos , Humanos , Isolamento de Pacientes , Estados Unidos , Viroses/prevenção & controle
11.
Proc Natl Acad Sci U S A ; 119(18): e2119396119, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35476524

RESUMO

Combatting Clostridioides difficile infections, a dominant cause of hospital-associated infections with incidence and resulting deaths increasing worldwide, is complicated by the frequent emergence of new virulent strains. Here, we employ whole-genome sequencing, high-throughput phenotypic screenings, and genome-scale models of metabolism to evaluate the genetic diversity of 451 strains of C. difficile. Constructing the C. difficile pangenome based on this set revealed 9,924 distinct gene clusters, of which 2,899 (29%) are defined as core, 2,968 (30%) are defined as unique, and the remaining 4,057 (41%) are defined as accessory. We develop a strain typing method, sequence typing by accessory genome (STAG), that identifies 176 genetically distinct groups of strains and allows for explicit interrogation of accessory gene content. Thirty-five strains representative of the overall set were experimentally profiled on 95 different nutrient sources, revealing 26 distinct growth profiles and unique nutrient preferences; 451 strain-specific genome scale models of metabolism were constructed, allowing us to computationally probe phenotypic diversity in 28,864 unique conditions. The models create a mechanistic link between the observed phenotypes and strain-specific genetic differences and exhibit an ability to correctly predict growth in 76% of measured cases. The typing and model predictions are used to identify and contextualize discriminating genetic features and phenotypes that may contribute to the emergence of new problematic strains.


Assuntos
Clostridioides difficile , Infecção Hospitalar , Clostridioides , Clostridioides difficile/genética , Variação Genética , Humanos , Biologia de Sistemas
12.
Proc Natl Acad Sci U S A ; 119(24): e2200830119, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35679344

RESUMO

The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.


Assuntos
Anti-Infecciosos , Cobre , Infecção Hospitalar , Nanopartículas Metálicas , Pele , Anti-Infecciosos/farmacologia , Cobre/farmacologia , Infecção Hospitalar/prevenção & controle , Escherichia coli/efeitos dos fármacos , Dedos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Porosidade , Pele/microbiologia
13.
Gut ; 73(4): 613-621, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38182137

RESUMO

OBJECTIVE: Contaminated duodenoscopes caused several hospital outbreaks. Despite efforts to reduce contamination rates, 15% of patient-ready duodenoscopes are still contaminated with gastrointestinal microorganisms. This study aimed to provide an overview of duodenoscope contamination over time, identify risk factors and study the effects of implemented interventions. DESIGN: Duodenoscope culture sets between March 2015 and June 2022 at a Dutch tertiary care centre were analysed. Contamination was defined as (1) the presence of microorganisms of oral or gastrointestinal origin (MGO) or (2) any other microorganism with ≥20 colony-forming units/20 mL (AM20). A logistic mixed effects model was used to identify risk factors and assess the effect of interventions, such as using duodenoscopes with disposable caps, replacing automated endoscope reprocessors (AER) and conducting audits in the endoscopy department. RESULTS: A total of 404 culture sets were analysed. The yearly contamination rate with MGO showed great variation, ranging from 14.3% to 47.5%. Contamination with AM20 increased up to 94.7% by 2022. For both MGO and AM20, the biopsy and suction channels were the most frequently contaminated duodenoscope components. The studied interventions, including audits, AER replacement and implementation of duodenoscopes with disposable caps, did not show a clear association with contamination rates. CONCLUSION: Duodenoscope contamination remains a significant problem, with high contamination rates despite several interventions. Reprocessing the biopsy and suction channels is especially challenging. Changes in the design of reusable duodenoscopes, such as enabling sterilisation or easily replaceable channels, are necessary to facilitate effective duodenoscope reprocessing and to eliminate the risk of duodenoscope-associated infections.


Assuntos
Infecção Hospitalar , Duodenoscópios , Humanos , Colangiopancreatografia Retrógrada Endoscópica , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Óxido de Magnésio , Estudos Retrospectivos , Centros de Atenção Terciária
14.
Clin Infect Dis ; 79(2): 412-419, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38442737

RESUMO

Over the past 10 years, there has been a rapid expansion in the use of extracorporeal membrane oxygenation (ECMO) in the care of patients with refractory cardiac or respiratory failure. Infectious diseases clinicians must reconcile conflicting evidence from limited studies as they develop practices at their own institutions, which has resulted in considerably different practices globally. This review describes infection control and prevention as well as antimicrobial prophylaxis strategies in this population. Data on diagnostics and treatment for patients receiving ECMO with a focus on diagnostic and antimicrobial stewardship is then examined. This review summarizes gaps in the current ECMO literature and proposes future needs, including developing clear definitions for infections and encouraging transparent reporting of practices at individual facilities in future clinical trials.


Assuntos
Infecção Hospitalar , Oxigenação por Membrana Extracorpórea , Controle de Infecções , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Gestão de Antimicrobianos , Adulto , Antibioticoprofilaxia , Doenças Transmissíveis
15.
Clin Infect Dis ; 78(1): 31-39, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37633257

RESUMO

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.


Assuntos
Bacteriemia , Infecção Hospitalar , Infecções por Klebsiella , Sepse , Humanos , Klebsiella pneumoniae , Infecção Hospitalar/epidemiologia , Mortalidade Hospitalar , Bacteriemia/microbiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Genômica
16.
Clin Infect Dis ; 78(2): 439-444, 2024 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-37463411

RESUMO

Many hospitals have stopped or are considering stopping universal admission testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and data suggesting surveillance testing is associated with fewer nosocomial infections. Preferences of diverse patient populations, particularly the hardest-hit communities, should be surveyed and used to inform prevention measures. Hospitals' ethical responsibility to protect patients from serious infections should predominate over concerns about costs, labor, and inconvenience. We call for more rigorous data on the incidence and morbidity of nosocomial SARS-CoV-2 infections and more research to help determine when to start, stop, and restart universal admission testing and other prevention measures.


Assuntos
COVID-19 , Infecção Hospitalar , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitalização
17.
Clin Infect Dis ; 78(5): 1204-1213, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38227643

RESUMO

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.


Assuntos
COVID-19 , Genoma Viral , Pessoal de Saúde , SARS-CoV-2 , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , Estudos Retrospectivos , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Análise de Rede Social , Busca de Comunicante , Genômica , Adulto Jovem , Adolescente , Criança , Idoso de 80 Anos ou mais , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Infecção Hospitalar/epidemiologia , Pré-Escolar
18.
Clin Infect Dis ; 79(1): 43-51, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38576380

RESUMO

BACKGROUND: Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. METHODS: We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. RESULTS: Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). CONCLUSIONS: Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico , Masculino , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Idoso , Staphylococcus aureus/isolamento & purificação , Países Baixos/epidemiologia , Diagnóstico por Imagem/métodos , Adulto , Infecção Hospitalar/microbiologia
19.
Clin Infect Dis ; 79(1): 60-69, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38527855

RESUMO

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator. RESULTS: DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar. CONCLUSIONS: Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.


Assuntos
Antibacterianos , Pneumonia Bacteriana , Pneumonia Associada à Ventilação Mecânica , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Antibacterianos/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Masculino , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Feminino , Estados Unidos , Ensaios Clínicos como Assunto , Infecção Hospitalar/tratamento farmacológico , Resultado do Tratamento , Pessoa de Meia-Idade , United States Food and Drug Administration , Idoso
20.
BMC Genomics ; 25(1): 727, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060939

RESUMO

BACKGROUND: Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. RESULTS: Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. CONCLUSIONS: This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Genótipo , Tipagem de Sequências Multilocus , Fenótipo , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Humanos , China , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Antibacterianos/farmacologia , Hospitais , Farmacorresistência Bacteriana Múltipla/genética , Infecção Hospitalar/microbiologia , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto
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