scholarly journals Clinical Evolution of New Delhi Metallo-β-Lactamase (NDM) Optimizes Resistance under Zn(II) Deprivation

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Guillermo Bahr ◽  
Luisina Vitor-Horen ◽  
Christopher R. Bethel ◽  
Robert A. Bonomo ◽  
Lisandro J. González ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Health Care Systems ◽  
Catalytic Efficiency ◽  
Catalytic Performance ◽  
System Response ◽  
New Delhi ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Care Systems

ABSTRACTCarbapenem-resistantEnterobacteriaceae(CRE) are rapidly spreading and taking a staggering toll on all health care systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family of carbapenemases are the Zn(II)-dependent β-lactamases, known as metallo-β-lactamases (MBLs). Among them, the New Delhi metallo-β-lactamase (NDM) has experienced the fastest and widest geographical spread. While other clinically important MBLs are soluble periplasmic enzymes, NDMs are lipoproteins anchored to the outer membrane in Gram-negative bacteria. This unique cellular localization endows NDMs with enhanced stability upon the Zn(II) starvation elicited by the immune system response at the sites of infection. Since the first report of NDM-1, new allelic variants (16 in total) have been identified in clinical isolates differing by a limited number of substitutions. Here, we show that these variants have evolved by accumulating mutations that enhance their stability or the Zn(II) binding affinityin vivo, overriding the most common evolutionary pressure acting on catalytic efficiency. We identified the ubiquitous substitution M154L as responsible for improving the Zn(II) binding capabilities of the NDM variants. These results also reveal that Zn(II) deprivation imposes a strict constraint on the evolution of this MBL, overriding the most common pressures acting on catalytic performance, and shed light on possible inhibitory strategies.

Measuring environmental performance in hospitals: a framework and process

2016 ◽  
Vol 20 (2) ◽  
pp. 52-64 ◽  
Author(s):  
Andreia Pasqualini Blass ◽  
Sergio E. Gouvea da Costa ◽  
Edson Pinheiro de Lima ◽  
Lilian Adriana Borges
Keyword(s):  
Literature Review ◽  
Environmental Performance ◽  
Health Care Systems ◽  
Field Studies ◽  
Content Type ◽  
Care Systems ◽  
Assessment And Monitoring ◽  
Environmental Performance Assessment ◽  
Review Current ◽  
New Framework

Purpose This paper aims to propose a new framework to define relevant and meaningful indicators for monitoring and assessing environmental performance to improve health-care systems and operations. Design/methodology/approach A comprehensive literature review followed by field studies conducted with ten hospitals in the southern region of Brazil underlined the scarcity of consistent frameworks applied in practice to measure, monitor and improve environmental performance. A new framework was developed and proposed to address this issue. The proposed framework is operationalized through a “process approach” and evaluated in terms of feasibility (Can the process be followed?), usability (Is the approach easily followed?) and utility (Are the results useful for managers?). Findings The paper proposes a framework and a process to evaluate the environmental performance in hospitals. Practical implications The proposed framework represents meaningful guidance to managers for strategy formalization, goal setting and environmental performance assessment and monitoring. Originality/value The paper proposes a systematic framework for measuring environmental performance in hospitals drawn from the literature review, current legislation and best practices reported in literature.

Feminine? Masculine? Androgynous leadership as a necessity in COVID-19

2020 ◽  
Vol 35 (7/8) ◽  
pp. 607-617
Author(s):  
Stacy Blake-Beard ◽  
Mary Shapiro ◽  
Cynthia Ingols
Keyword(s):  
Leadership Style ◽  
Health Care Systems ◽  
Leadership Skills ◽  
Leadership Traits ◽  
Political Leaders ◽  
Content Type ◽  
Care Systems ◽  
The Impact ◽  
The Relationship ◽  
Practical Implications

Purpose The purpose of this paper is to explore the relationship between leaders’ expressed traits and their impact on their country’s COVID-19 outcomes. Some leaders are over relying on masculine traits and dismissing feminine traits. An alternative – androgynous leadership – supports leaders in drawing from the full portfolio of behaviors. Design/methodology/approach This paper has a theoretical approach using an extensive review of the literature. Findings Leaders can take a number of actions to fully embrace androgynous leadership. These actions include building a diverse “tempered” team, communicating with respect, recognizing the impact of framing and moving from autopilot to realizing their best androgynous self. Research limitations/implications Research limitations include a critique of Bem’s framework as outdated and dichotomous; a categorization of feminine, masculine and neutral behaviors that is determined by the authors; and a focus on leadership style that does not take other dimensions, such as health-care systems, into account. Practical implications The authors propose that an “androgynous” leadership style has been used effectively by some political leaders around the globe in the COVID-19 crisis. The COVID-19 context has provided a laboratory for developing and building competence as androgynous leaders. Social implications The mental capacity to look at a situation, pause and explicitly select effective behavior is necessary, but oftentimes, it is not put into practice. By not drawing from a larger portfolio of androgynous behaviors, the opportunity for leaders to their best work is missed. Originality/value There is an acknowledgement of the benefits of the combination of masculine and feminine leadership traits. There are also clear recommendations supporting leaders in developing their androgynous leadership skills.

The making and sustaining of leaders in health care

2019 ◽  
Vol 33 (2) ◽  
pp. 241-262 ◽  
Author(s):  
Terry J. Boyle ◽  
Kieran Mervyn
Keyword(s):  
Health Care ◽  
Community Health ◽  
Health Care Services ◽  
Health Care Systems ◽  
Structured Interviews ◽  
Healthcare Provision ◽  
Triple Aim ◽  
Content Type ◽  
Care Services ◽  
Care Systems

Purpose Many nations are focussing on health care’s Triple Aim (quality, overall community health and reduced cost) with only moderate success. Traditional leadership learning programmes have been based on a taught curriculum, but the purpose of this paper is to demonstrate more modern approaches through procedures and tools. Design/methodology/approach This study evolved from grounded and activity theory foundations (using semi-structured interviews with ten senior healthcare executives and qualitative analysis) which describe obstructions to progress. The study began with the premise that quality and affordable health care are dependent upon collaborative innovation. The growth of new leaders goes from skills to procedures and tools, and from training to development. Findings This paper makes “frugal innovation” recommendations which while not costly in a financial sense, do have practical and social implications relating to the Triple Aim. The research also revealed largely externally driven health care systems under duress suffering from leadership shortages. Research limitations/implications The study centred primarily on one Canadian community health care services’ organisation. Since healthcare provision is place-based (contextual), the findings may not be universally applicable, maybe not even to an adjacent community. Practical implications The paper dismisses outdated views of the synonymity of leadership and management, while encouraging clinicians to assume leadership roles. Originality/value This paper demonstrates how health care leadership can be developed and sustained.

scholarly journals In Vivo Efficacy of Novel Monobactam LYS228 in Murine Models of Carbapenemase-Producing Klebsiella pneumoniae Infection

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
W. J. Weiss ◽  
M. E. Pulse ◽  
P. Nguyen ◽  
E. J. Growcott
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Development ◽  
Murine Models ◽  
Bacterial Burden ◽  
In Vivo Efficacy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Infection Models ◽  
Resistant Strains

ABSTRACT LYS228 has potent antibacterial activity against carbapenem-resistant strains of Enterobacteriaceae. LYS228 was efficacious in neutropenic thigh models established with Klebsiella pneumoniae producing KPC-2 or NDM-1; pretreatment with uranyl nitrate considerably shifted calculated static doses of LYS228. In murine ascending pyelonephritis, LYS228 reduced bacterial burden in kidney, urine, and bladder. The successful treatment of murine infection models established with carbapenem-resistant K. pneumoniae further supports the clinical development of LYS228.

scholarly journals Evaluation of the EDTA-Modified Carbapenem Inactivation Method for Detecting Metallo-β-Lactamase-Producing Pseudomonas aeruginosa

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Christian M. Gill ◽  
Maxwell J. Lasko ◽  
Tomefa E. Asempa ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Test Performance ◽  
New Delhi ◽  
Large Collection ◽  
Testing Methods ◽  
Prolonged Incubation ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Genotypic Profile

ABSTRACT The prevalence of carbapenem-resistant Pseudomonas aeruginosa is increasing. Identification of carbapenemase-producing P. aeruginosa will have therapeutic, epidemiological, and infection control implications. This study evaluated the performance of the EDTA-modified carbapenem inactivation method (eCIM) in tandem with the modified carbapenem inactivation method (mCIM) against a large collection of clinical P. aeruginosa isolates (n = 103) to provide clinicians a phenotypic test that not only identifies carbapenemase production but also distinguishes between metallo-β-lactamase and serine-carbapenemase production in P. aeruginosa. The mCIM test was performed according to Clinical and Laboratory Standards Institute guidelines, while the eCIM was conducted as previously described for Enterobacteriaceae. Test performance was compared to the genotypic profile as the reference. mCIM testing successfully categorized 91% (112/123) of P. aeruginosa isolates as carbapenemases or non-carbapenemase producers, with discordant isolates being primarily Guiana extended-spectrum (GES)-type producers. To increase the sensitivity of the mCIM for GES-harboring isolates, a double inoculum, prolonged incubation, or both was evaluated, with each modification improving sensitivity to 100% (12/12). Upon eCIM testing, all Verona integrin-encoded metallo-β-lactamases (VIM; n = 27) and New Delhi metallo-β-lactamases (NDM; n = 13) tested had 100% concordance to their genotypic profiles, whereas all Klebsiella pneumoniae carbapenemase (KPC; n = 8) and GES (n = 12) isolates tested negative, as expected, in the presence of EDTA. The eCIM failed to identify all imipenemase (IMP)-producing (n = 22) and Sao Paulo metallo-β-lactamase (SPM)-producing (n = 14) isolates. KPC-, VIM-, and NDM-producing P. aeruginosa were well defined by the conventional mCIM and eCIM testing methods; additional modifications appear required to differentiate GES-, IMP-, and SPM-producing isolates.

First evidences from “lean & safety” projects

2015 ◽  
Vol 7 (2/3) ◽  
pp. 245-259 ◽  
Author(s):  
Maria Crema ◽  
Chiara Verbano ◽  
Maria Laura Chiozza
Keyword(s):  
Design Methodology ◽  
Health Care Systems ◽  
Future Research ◽  
Successful Implementation ◽  
Key Factors ◽  
Content Type ◽  
Academic Literature ◽  
Integrated Methodology ◽  
Care Systems ◽  
Sustainable Health

Purpose – The purpose of this paper is to investigate the significant features that characterize these projects: organizational aspects, phases and activities, tools, techniques, practices and key factors for successful implementation. No studies in the academic literature have yet focused on the relation between healthcare lean management (HLM) and clinical risk management (CRM) to enhance multiple aspects of performance, although the possibility of implementing “lean & safety” projects has been highlighted. Design/methodology/approach – Two significant projects have been selected from the same Italian hospital in two different fields of application. Within- and cross-case analyses have been performed to obtain useful findings. Findings – The results suggest that HLM can provide support for CRM, and an integrated methodology should be considered. The first indications concerning how this new synergistic methodology may be developed are provided and these should stimulate future research, testing and exploiting the methodology in other contexts. Originality/value – From the results of this paper, guidelines for the implementation of a “lean & safety” project could be developed to improve the management of clinical processes pursuing multiple objectives. This study could contribute to the development of safer and more sustainable health care systems for the benefit of the entire community.

scholarly journals Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kasturi Banerjee ◽  
Michael P. Motley ◽  
Elizabeth Diago-Navarro ◽  
Bettina C. Fries
Keyword(s):  
Klebsiella Pneumoniae ◽  
Capsular Polysaccharide ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Reactive Properties

ABSTRACT Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.

scholarly journals Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Hea-Jin Jung ◽  
Eric R. Littmann ◽  
Ruth Seok ◽  
Ingrid M. Leiner ◽  
Ying Taur ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genetic Factors ◽  
Intestinal Lumen ◽  
Intestinal Colonization ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Gut Colonization ◽  
Colonization Factors

ABSTRACT A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp. Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-Kp. IMPORTANCE Klebsiella pneumoniae is a common cause of bloodstream infections in immunocompromised and hospitalized patients, and over the last 2 decades, some strains have acquired resistance to nearly all available antibiotics, including broad-spectrum carbapenems. The U.S. Centers for Disease Control and Prevention has listed carbapenem-resistant K. pneumoniae (CR-Kp) as an urgent public health threat. Dense colonization of the intestine by CR-Kp and other antibiotic-resistant bacteria is associated with an increased risk of bacteremia. Reducing the density of gut colonization by CR-Kp is likely to reduce their transmission from patient to patient in health care facilities as well as systemic infections. How CR-Kp expands and persists in the gut lumen, however, is poorly understood. Herein, we generated a highly saturated mutant library in a multidrug-resistant K. pneumoniae strain and identified genetic factors that are associated with dense gut colonization by K. pneumoniae. This study sheds light on host colonization by K. pneumoniae and identifies potential colonization factors that contribute to high-density persistence of K. pneumoniae in the intestine.

scholarly journals LncRNA KCNQ1OT1 attenuates sepsis-induced myocardial injury via regulating miR-192-5p/XIAP axis

2020 ◽  
Vol 245 (7) ◽  
pp. 620-630 ◽  
Author(s):  
Fangyuan Sun ◽  
Weifang Yuan ◽  
Hao Wu ◽  
Gang Chen ◽  
Yuxia Sun ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
Health Care Systems ◽  
Cardiac Injury ◽  
Convincing Evidence ◽  
Luciferase Reporter ◽  
H9c2 Cardiomyocytes ◽  
Care Systems

Myocardial dysfunction is a prime cause of death in sepsis. This study is to delve into the function of lncRNA KCNQ1OT1 in myocardial injury induced by sepsis. Sepsis-induced myocardial injury model in rat was initiated by intraperitoneally injecting of LPS (10 mg/kg) in vivo, and cardiomyocyte H9c2 was treated with LPS to mimic sepsis in vitro. KCNQ1OT1 and miR-192-5p expressions were detected by qRT-PCR. The cell viability was probed with CCK-8 experiment and the apoptosis of the cardiomyocytes was tested using flow cytometry analysis. Western blot was operated to determine apoptosis-related proteins expressions. ELISA was used to evaluate the levels of TNF-α, IL-6, and IL-1β. Bioinformatics analysis, RT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation experiment were utilized to detect the interrelation of genes. Herein, we proved that KCNQ1OT1 was considerably down-regulated, whereas miR-192-5p was markedly increased in myocardial tissues of septic rats. KCNQ1OT1 interrelated with miR-192-5p, and negatively modulated its expression levels. Overexpression of KCNQ1OT1 or the transfection of miR-192-5p inhibitors greatly facilitated the viability and impeded the apoptosis of H9c2 cardiomyocytes. miR-192-5p paired with the 3ʹUTR of XIAP, and repressed its protein expression, and XIAP was modulated positively by KCNQ1OT1. In conclusion, our work indicates that down-regulation of KCNQ1OT1 advances cardiac injury through regulating miR-192-5p/XIAP axis during sepsis. Impact statement Sepsis-induced cardiomyopathy remains to be a major challenge to health care systems around the globe. There are no known therapies currently available that can cure the disease. This study provides convincing evidence that KCNQ1OT1 could attenuate sepsis-mediated myocardial injury. We further demonstrate that the beneficial function of KCNQ1OT1 was achieved by regulating the miR-192-5p/XIAP axis. We therefore found a new mechanism of cardioprotective effect of KCNQ1OT1, one which also offers a novel theoretical basis for the therapy of sepsis-induced cardiomyopathy.

A pentaplex real-time PCR assay for rapid identification of major beta-lactamase genes KPC, NDM, CTX, CMY, and OXA-48 directly from bacteria in blood

2021 ◽  
Vol 70 (12) ◽  
Author(s):  
Taalin R. Hoj ◽  
Bradley McNeely ◽  
Kylie Webber ◽  
Evelyn Welling ◽  
William G. Pitt ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Real Time ◽  
Real Time Pcr ◽  
Type Species ◽  
New Delhi ◽  
Beta Lactamase ◽  
Content Type ◽  
Link Type ◽  
Carbapenem Resistant

Introduction. Antibiotic resistance, particularly in cases of sepsis, has emerged as a growing global public health concern and economic burden. Current methods of blood culture and antimicrobial susceptibility testing of agents involved in sepsis can take as long as 3–5 days. It is vital to rapidly identify which antimicrobials can be used to effectively treat sepsis cases on an individual basis. Here, we present a pentaplex, real-time PCR-based assay that can quickly identify the most common beta-lactamase genes ( Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX-M); cephamycin AmpC beta-lactamases (CMY); and Oxacillinase-48 (OXA-48)) from pathogens derived directly from the blood of patients presenting with bacterial septicemia. Aim. To develop an assay which can rapidly identify the most common beta-lactamase genes in Carbapenem-resistant Enterobacteriaceae bacteria (CREs) from the United States. Hypothesis/Gap Statement. Septicemia caused by carbapenem-resistant bacteria has a death rate of 40–60 %. Rapid diagnosis of antibiotic susceptibility directly from bacteria in blood by identification of beta-lactamase genes will greatly improve survival rates. In this work, we develop an assay capable of concurrently identifying the five most common beta-lactamase and carbapenemase genes. Methodology. Primers and probes were created which can identify all subtypes of Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX); cephamycin AmpC beta-lactamase (CMY); and oxacillinase-48 (OXA-48). The assay was validated using 13 isolates containing various PCR targets from the Centre for Disease Control Antimicrobial Resistance Isolate Bank Enterobacterales Carbapenemase Diversity Panel. Blood obtained from volunteers was spiked with CREs and bacteria were separated, lysed, and subjected to analysis via the pentaplex assay. Results. This pentaplex assay successfully identified beta-lactamase genes derived from bacteria separated from blood at concentrations of 4–8 c.f.u. ml−1. Conclusion. This assay will improve patient outcomes by supplying physicians with critical drug resistance information within 2 h of septicemia onset, allowing them to prescribe effective antimicrobials corresponding to the resistance gene(s) present in the pathogen. In addition, information supplied by this assay will lessen the inappropriate use of broad-spectrum antimicrobials and prevent the evolution of further antibiotic resistance.

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