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1.
JMIR Res Protoc ; 13: e64433, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39208425

RESUMO

BACKGROUND: Gay, bisexual, and other men who have sex with men living with HIV (GBMSM-LWH) in the United States bear a heavy burden of bacterial sexually transmitted infections (STIs). Timely diagnosis and treatment are key to prevention. Only a few studies have combined home specimen self-collection for bacterial STI screening with live audio and video (AV) conferencing. None have focused on GBMSM-LWH or incorporated motivational interviewing (MI), a client-centered, strengths-based counseling approach that seeks to support individuals to create positive behavioral change. OBJECTIVE: Our study seeks to investigate the feasibility and acceptability of an MI-based telehealth intervention that integrates home specimen self-collection from different anatomical sites of possible exposure and MI delivered via live AV conferencing to engage sexually active GBMSM-LWH in bacterial STI screening. METHODS: Participants are being recruited from across the United States via advertising on mobile dating apps and social networking sites and via peer referral. Phase 1 involves piloting the delivery of an innovative telehealth intervention for bacterial STI screening to 75 GBMSM-LWH. Our intervention includes three components: (1) a pretest live AV conferencing session involving an MI-guided discussion to elicit awareness of bacterial STIs; fill any knowledge gaps; bolster the perceived importance of regularly testing for gonorrhea, chlamydia, and syphilis; and build self-efficacy for specimen self-collection; (2) home self-collection and return via mail of a urine sample (for gonorrhea and chlamydia testing), a throat swab (for gonorrhea and chlamydia testing), a rectal swab (for gonorrhea and chlamydia testing), and a finger-stick blood sample (for syphilis testing); and (3) a posttest live AV conferencing session involving an MI-guided discussion to prepare participants for receiving test results and formulate personalized action plans for seeking treatment (if warranted) and repeat testing. Descriptive statistics and progression ratios will be calculated, and potential variations in our intervention's feasibility and acceptability will be numerically summarized and graphically visualized. Phase 2 involves elucidating attitudes, facilitators, and barriers related to engaging in each intervention component via semistructured in-depth interviews with a purposive subsample of 20 participants who complete progressively smaller subsets of the pretest session, specimen return for bacterial STI testing, and the posttest session. Thematic analysis will be used to identify, analyze, and report patterns in the data. Quantitative and qualitative data will be integrated at the design, methods, interpretation, and reporting levels. RESULTS: Study procedures were approved by the Institutional Review Board at the University of Michigan in September 2023. Participant recruitment began in April 2024. CONCLUSIONS: Our study will advance multiple goals of the STI National Strategic Plan for the United States for 2021 to 2025, specifically those pertaining to preventing new STIs; accelerating progress in STI research, technology, and innovation; and reducing STI-related health disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT06100250; https://www.clinicaltrials.gov/study/NCT06100250. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64433.


Assuntos
Estudos de Viabilidade , Entrevista Motivacional , Doenças Bacterianas Sexualmente Transmissíveis , Telemedicina , Adulto , Humanos , Masculino , Homossexualidade Masculina/psicologia , Programas de Rastreamento/métodos , Programas de Rastreamento/psicologia , Entrevista Motivacional/métodos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Minorias Sexuais e de Gênero/psicologia , Doenças Bacterianas Sexualmente Transmissíveis/diagnóstico , Doenças Bacterianas Sexualmente Transmissíveis/prevenção & controle , Estados Unidos/epidemiologia
2.
Int J STD AIDS ; : 9564624241273830, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138867

RESUMO

BACKGROUND: South Asian gay, bisexual, and other men who have sex with men (GBM) in the United States have been persistently overlooked in HIV research and programming. To address this limitation, this article describes their HIV-related knowledge, risk perception, and minority stressors, with a focus on identifying variations between American-born individuals and immigrants. METHODS: Participants were recruited from April-July 2022 through social media advertising and peer referral and surveyed about their sociodemographic and HIV-related behavioral characteristics. Previously validated scales were used to assess their HIV-related knowledge, risk perception, disclosure of sexual identity, experienced homophobia, and perceived racism within the sexual and gender minority community. Mann-Whitney-Wilcoxon tests were conducted to compare those born in the United States and those born abroad. RESULTS: Of the 112 participants, 26 (23.21%) were American-born individuals and 86 (76.79%) were immigrants. Despite similar levels of sexual risk behaviors, such as having multiple male sex partners, engaging in condomless anal sex, and using alcohol or drugs immediately before or during sex, immigrants had lower levels of HIV-related knowledge (p = .0480) and risk perception (p = .0114) compared to American-born individuals. Immigrants were also less likely to have disclosed their sexual identity to family, friends, and society compared to American-born individuals (p = .0004). No differences were identified with respect to experiences of homophobia (p = .2303) or perceptions of racism (p = .4011). CONCLUSION: Comprehensive HIV prevention efforts that address the social and cultural norms of South Asian GBM in the United States are needed.

5.
J Bone Jt Infect ; 9(1): 87-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601005

RESUMO

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

6.
Conserv Biol ; : e14249, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488313

RESUMO

Conservationists increasingly position conservation that is mutually beneficial to people and biodiversity on the promise of empowerment of people through participatory discourse, metrics, processes, and outcomes. Empowerment represents multidimensional concepts and theories that permeate the interlinking levels of power, from the psychological to the political, and social scales in which conservation operates. The multifaceted nature of empowerment makes it challenging to understand, pursue, and evaluate as a central philosophical commitment and goal-oriented practice in conservation. Moreover, definitional and methodological uncertainty may disempower interested and affected groups because they can foster conceptual assumptions that reinforce institutionalized barriers to systemic changes. Despite these complexities, there are no targeted reviews of empowerment in conservation. We conducted a scoping review of the conservation literature to synthesize the meanings and uses of empowerment in the field. We reviewed 121 of the most cited conservation articles that invoked or assessed empowerment from 1992 to 2017 to document geographic, conceptual, and methodological trends in the scales and theories of empowerment deployed by conservationists. Research claiming or assessing empowerment through conservation often focused on communities in the Global South. Most studies relied on qualitative and mixed methods (78%) collected largely from male or non-Indigenous participants. Few studies (30%) defined the 20 types of empowerment they referenced. Fewer studies (3%) applied empowerment theories in their work. Our findings show that empowerment discourse of local and Indigenous communities permeates the discourse of people-centered conservation. Yet, overreliance on empowerment's rhetorical promise and minimal engagement with theory (e.g., postcolonial theory) risks disempowering people by obscuring empowerment's foundational value to conservation and communities and oversimplifying the complex realities of people-centered conservation. Lasting change could come from more meaningful engagement with empowerment, including coproducing definitions and measures with and for disempowered social groups to tackle widespread power disparities in conservation today.


El alcance del empoderamiento para la conservación y las comunidades Resumen Con frecuencia los conservacionistas posicionan a la conservación como benéfica para las personas y la biodiversidad mediante discursos, medidas, procesos y resultados participativos que prometen el empoderamiento de la gente. El empoderamiento representa conceptos y teorías multidimensionales que permean los niveles interconectados de poder, desde el psicológico al político, y las escalas sociales en las que opera la conservación. La naturaleza multifacética del empoderamiento complica que se entienda, se dé seguimiento y se evalúe como un compromiso filosófico central y una práctica orientada hacia las metas dentro de la conservación. Además, la incertidumbre metodológica y de definición pueden restar autoridad a los grupos interesados o afectados pues pueden promover suposiciones conceptuales que refuerzan las barreras institucionales de los cambios sistémicos. A pesar de estas complejidades, no existen revisiones focalizadas del empoderamiento en la conservación. Realizamos una revisión de alcance de la literatura de conservación para sintetizar los significados y usos de la palabra empoderamiento en este campo. Revisamos 121 de los artículos sobre conservación más citados que invocaron o evaluaron el empoderamiento entre 1992 y 2017 para documentar las tendencias geográficas, conceptuales y metodológicas en las escalas y teorías del empoderamiento usadas por los conservacionistas. La mayoría de los artículos que afirmaban o evaluaban el empoderamiento por medio de la conservación se enfocaron en comunidades del Sur Global. La mayoría de los estudios dependieron de métodos cualitativos y mixtos (78%) tomados principalmente de participantes masculinos o no indígenas. Pocos estudios (30%) definieron los 20 tipos de empoderamiento que referenciaron. Todavía menos estudios (3%) aplicaron las teorías de empoderamiento a su trabajo. Nuestros descubrimientos muestran que el discurso de empoderamiento de las comunidades locales e indígenas permea el discurso de la conservación centrada en la gente. Sin embargo, depender en exceso de la promesa retórica del empoderamiento e involucrarse en lo mínimo con la teoría (p. ej.: teoría postcolonial) arriesga que la gente se pierda autoridad al oscurecer el valor fundamental que tiene el empoderamiento para la conservación y las comunidades y simplificar sobremanera las realidades complejas de la conservación centrada en las personas. El cambio duradero podría venir de involucrarse de forma más significativa con el empoderamiento, lo que incluye la coproducción de definiciones y medidas con y para los grupos sociales no empoderados para resolver la disparidad de poder que existe hoy en día en la conservación.

7.
Future Microbiol ; 19: 61-72, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180334

RESUMO

Rapidly detecting and identifying pathogens is crucial for appropriate antimicrobial therapy in patients with sepsis. Conventional diagnostic methods have been a great asset to medicine, though they are time consuming and labor intensive. This work will enable healthcare professionals to understand the bacterial community better and enhance their diagnostic capacity by using novel molecular methods that make obtaining quicker, more precise results possible. The authors discuss and critically assess the merits and drawbacks of molecular testing and the added value of these tests, including the shift turnaround time, the implication for clinicians' decisions, gaps in knowledge, future research directions and novel insights or innovations. The field of antimicrobial molecular testing has seen several novel insights and innovations to improve the diagnosis and management of infectious diseases.


Sepsis is a life-threatening reaction to an infection. This infection is normally caused by a bacteria. Identifying the bacteria that has caused the infection is very important to choosing the best treatment. This is usually done using molecular testing. This article discusses the advantages and disadvantages of molecular testing, which tests are available and the value of these tests in clinical practice, the implication of molecular tests for clinicians' decisions and the gaps in our knowledge. It also discusses future innovations in molecular testing.


Assuntos
Anti-Infecciosos , Sepse , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/microbiologia , Bactérias/genética , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Fatores de Tempo
11.
Eur J Clin Microbiol Infect Dis ; 42(2): 169-176, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36474096

RESUMO

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.


Assuntos
Artrite Infecciosa , Kingella kingae , Criança , Adulto , Humanos , Estudos Retrospectivos , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Reação em Cadeia da Polimerase , Líquido Sinovial/microbiologia , Kingella kingae/genética
12.
Urogynecology (Phila) ; 28(8): 506-517, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256964

RESUMO

IMPORTANCE: The rate of genitourinary tract injury (GUTI) following pelvic organ prolapse (POP) surgery is presently ill-defined and based on relatively small trials with short follow-up time. Given the potential for higher risk of injury with POP, a better understanding of this type of injury is important for patient counseling. OBJECTIVES: The objective of this study was to identify the incidence and risk factors of GUTI related to POP surgery. STUDY DESIGN: Women undergoing POP surgery between 2010 and 2019 were identified using Current Procedural Terminology codes in the Premier Healthcare Database. The primary outcome was GUTI, defined as bladder or ureteral injury, and vesicovaginal or ureterovaginal fistula within 1 year of surgery. Genitourinary tract injury was identified using International Classification of Diseases and Current Procedural Terminology codes. Patients were divided into those with and without GUTI. Differences between groups were evaluated using the Student t test, Wilcoxon rank-sum test, and Fisher exact test as appropriate. Multivariable logistic regression was used to evaluate the independent predictors of GUTI. RESULTS: One hundred thirty-nine thousand one hundred fifty-eight surgical procedures for POP were captured between 2010 and 2019. The rate of GUTI was 1.10%: 0.48% bladder, 0.64% ureteral injuries, and 0.01% fistulas. The most significant variables associated with any GUTI were as follows: adhesiolysis (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.07-6.51), blood transfusion (aOR, 3.67; 95% CI, 1.34-10.04), and low-volume surgeons (<12 cases per year) (aOR, 1.68; 95% CI, 1.60-1.77), nonurologic or gynecologic surgeon specialty (aOR, 1.62; 95% CI, 1.49-2.00), and uterosacral suspension (aOR, 1.30; 95% CI, 1.13-1.49). CONCLUSIONS: The rate of GUTI following POP surgery is lower than has previously been reported. Surgeon experience and specialty and surgical approach may affect GUTI incidence.


Assuntos
Prolapso de Órgão Pélvico , Fístula Urinária , Feminino , Humanos , Incidência , Prolapso de Órgão Pélvico/epidemiologia , Fatores de Risco , Fístula Urinária/etiologia , Bexiga Urinária
13.
Antimicrob Agents Chemother ; 66(8): e0021622, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35856662

RESUMO

Modern medicine is threatened by the rising tide of antimicrobial resistance, especially among Gram-negative bacteria, where resistance to ß-lactams is most often mediated by ß-lactamases. The penicillin and cephalosporin ascendancies were, in their turn, ended by the proliferation of TEM penicillinases and CTX-M extended-spectrum ß-lactamases. These class A ß-lactamases have long been considered the most important. For carbapenems, however, the threat is increasingly from the insidious rise of a class D carbapenemase, OXA-48, and its close relatives. Over the past 20 years, OXA-48 and "OXA-48-like" enzymes have proliferated to become the most prevalent enterobacterial carbapenemases across much of Europe, Northern Africa, and the Middle East. OXA-48-like enzymes are notoriously difficult to detect because they often cause only low-level in vitro resistance to carbapenems, meaning that the true burden is likely underestimated. Despite this, they are associated with carbapenem treatment failures. A highly conserved incompatibility complex IncL plasmid scaffold often carries blaOXA-48 and may carry other antimicrobial resistance genes, leaving limited treatment options. High conjugation efficiency means that this plasmid is sometimes carried by multiple Enterobacterales in a single patient. Producers evade most ß-lactam-ß-lactamase inhibitor combinations, though promising agents have recently been licensed, notably ceftazidime-avibactam and cefiderocol. The molecular machinery enabling global spread, current treatment options, and the development pipeline of potential new therapies for Enterobacterales that produce OXA-48-like ß-lactamases form the focus of this review.


Assuntos
Inibidores de beta-Lactamases , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Enterobacteriaceae , Humanos , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamases/genética
14.
Genome Med ; 13(1): 182, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34784976

RESUMO

BACKGROUND: Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. METHODS: CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. RESULTS: An 8-h CMg workflow was 92% sensitive (95% CI, 75-99%) and 82% specific (95% CI, 57-96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of ß-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. CONCLUSION: CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.


Assuntos
COVID-19/patologia , Infecção Hospitalar/transmissão , Metagenômica , Antibacterianos/uso terapêutico , COVID-19/virologia , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Corynebacterium/genética , Corynebacterium/isolamento & purificação , Infecção Hospitalar/microbiologia , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Humanos , Unidades de Terapia Intensiva , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/isolamento & purificação , Análise de Sequência de DNA , beta-Lactamases/genética
15.
J Med Microbiol ; 70(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33861190

RESUMO

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus.Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation.Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.


Assuntos
Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , Coinfecção/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , COVID-19/microbiologia , Coinfecção/microbiologia , Estado Terminal , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Inglaterra/epidemiologia , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
16.
J Glob Antimicrob Resist ; 22: 826-831, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32712381

RESUMO

BACKGROUND: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.


Assuntos
Infecção Hospitalar , Infecções por Bactérias Gram-Negativas , Estudos de Casos e Controles , Estado Terminal , Infecção Hospitalar/epidemiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Estudos Retrospectivos , Singapura , Medicina Estatal
17.
Antimicrob Agents Chemother ; 64(10)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32690645

RESUMO

Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-ß-lactamase (MBL) enzymes are a particular concern and are increasingly disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem resistance in vivo, under zinc limitation, than in vitro Owing to their unique structure and function and their diversity, MBLs pose a particular challenge for drug development. They evade all recently licensed ß-lactam-ß-lactamase inhibitor combinations, although several stable agents and inhibitor combinations are at various stages in the development pipeline. These potential therapies, along with the epidemiology of producers and current treatment options, are the focus of this review.


Assuntos
Antibacterianos , beta-Lactamases , Antibacterianos/uso terapêutico , Ásia , Bactérias Gram-Negativas , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamases/genética
18.
mSphere ; 5(3)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522780

RESUMO

Using live microbes as therapeutic candidates is a strategy that has gained traction across multiple therapeutic areas. In the skin, commensal microorganisms play a crucial role in maintaining skin barrier function, homeostasis, and cutaneous immunity. Alterations of the homeostatic skin microbiome are associated with a number of skin diseases. Here, we present the design of an engineered commensal organism, Staphylococcus epidermidis, for use as a live biotherapeutic product (LBP) candidate for skin diseases. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. We therefore constructed an auxotrophic strain of S. epidermidis that requires exogenously supplied d-alanine. The S. epidermidis NRRL B-4268 Δalr1 Δalr2 Δdat strain (SEΔΔΔ) contains deletions of three biosynthetic genes: two alanine racemase genes, alr1 and alr2 (SE1674 and SE1079), and the d-alanine aminotransferase gene, dat (SE1423). These three deletions restricted growth in d-alanine-deficient medium, pooled human blood, and skin. In the presence of d-alanine, SEΔΔΔ colonized and increased expression of human ß-defensin 2 in cultured human skin models in vitro. SEΔΔΔ showed a low propensity to revert to d-alanine prototrophy and did not form biofilms on plastic in vitro. These studies support the potential safety and utility of SEΔΔΔ as a live biotherapeutic strain whose growth can be controlled by d-alanine.IMPORTANCE The skin microbiome is rich in opportunities for novel therapeutics for skin diseases, and synthetic biology offers the advantage of providing novel functionality or therapeutic benefit to live biotherapeutic products. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. This study presents the design and in vitro evidence of a skin commensal whose growth can be controlled through d-alanine. The basis of this strain will support future clinical studies of this strain in humans.


Assuntos
Alanina/metabolismo , Terapia Biológica/métodos , Pele/microbiologia , Staphylococcus epidermidis/crescimento & desenvolvimento , Staphylococcus epidermidis/genética , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Humanos , Microbiota/efeitos dos fármacos , Simbiose
19.
Laryngoscope ; 129(4): 852-857, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30570749

RESUMO

OBJECTIVES/HYPOTHESIS: To investigate whether radiologist-produced imaging reports containing the terms mastoiditis or mastoid opacification clinically correlate with physical examination findings of mastoiditis. Additionally, to investigate whether and how often otolaryngology was unnecessarily consulted and inappropriate antibiotic therapy was initiated. STUDY DESIGN: Retrospective chart review within a large community hospital setting. METHODS: A retrospective review of 160 patients who had imaging tests performed for nonotolaryngology indications from January 2011 to March 2017 at our facility. Indications, patient demographics, otolaryngology consultations, and new antibiotics started were recorded. Physical examinations were documented. RESULTS: Physical examination revealed that only 14 of 160 patients (8.8%) had clinical evidence of otologic disease. However, of the 160 patients meeting the inclusion criteria, 18 (11.3%) received an otolaryngology consultation, and 18 (11.3%) had antibiotics started. Eleven of the 18 patients in each group (61.1%) had a normal physical examination, two (11.1%) had serous otitis media, one (5.6%) had chronic otitis media, and four (22.2%) had acute otitis media. No patients were found to have clinical mastoiditis. χ2 analysis revealed no significance in the radiologic diagnosis of mastoiditis versus mastoid opacification in relation to physicians requesting otolaryngology consultations (P = .241) or starting patients on antibiotics (P = .951). CONCLUSIONS: This study highlights the prevalence of incidental but clinically insignificant opacification of the mastoid cavity. We believe that nonotolaryngology physicians are, overall, competent to correlate such radiologic findings clinically and to prevent unnecessary consultations and inappropriate treatment, which add significant costs to our overstretched healthcare system. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:852-857, 2019.


Assuntos
Otopatias/diagnóstico por imagem , Mastoidite/diagnóstico por imagem , Otolaringologia/estatística & dados numéricos , Radiografia/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Competência Clínica/estatística & dados numéricos , Otopatias/complicações , Feminino , Humanos , Masculino , Processo Mastoide/diagnóstico por imagem , Mastoidite/etiologia , Pessoa de Meia-Idade , Otite Média/complicações , Otite Média/diagnóstico por imagem , Exame Físico/estatística & dados numéricos , Estudos Retrospectivos , Procedimentos Desnecessários/estatística & dados numéricos , Adulto Jovem
20.
Lancet Infect Dis ; 18(12): e368-e378, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30172580

RESUMO

Mitigating the risks of antibiotic resistance requires a horizon scan linking the quality with the quantity of data reported on drivers of antibiotic resistance in humans, arising from the human, animal, and environmental reservoirs. We did a systematic review using a One Health approach to survey the key drivers of antibiotic resistance in humans. Two sets of reviewers selected 565 studies from a total of 2819 titles and abstracts identified in Embase, MEDLINE, and Scopus (2005-18), and the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and WHO (One Health data). Study quality was assessed in accordance with Cochrane recommendations. Previous antibiotic exposure, underlying disease, and invasive procedures were the risk factors with most supporting evidence identified from the 88 risk factors retrieved. The odds ratios of antibiotic resistance were primarily reported to be between 2 and 4 for these risk factors when compared with their respective controls or baseline risk groups. Food-related transmission from the animal reservoir and water-related transmission from the environmental reservoir were frequently quantified. Uniformly quantifying relationships between risk factors will help researchers to better understand the process by which antibiotic resistance arises in human infections.


Assuntos
Bactérias/efeitos dos fármacos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/veterinária , Farmacorresistência Bacteriana , Microbiologia Ambiental , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Transmissão de Doença Infecciosa , Feminino , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
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