Carbapenemase-producing organisms: a global scourge

The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid–based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control

When Antibiotics Fail: The Expert Panel on the Potential Socio-Economic Impacts of Antimicrobial Resistance in Canada

Antimicrobials are life savers in Canada, enabling modern healthcare and playing a central role in agriculture. They have reduced the economic, medical, and social burden of infectious diseases and are part of many routine medical interventions, such as caesarean sections, joint replacements, and tonsillectomies. As use of antimicrobials has increased, bacteria evolved to become resistant, resulting in drugs that are no longer effective at treating infections. Antimicrobial resistance (AMR) is increasing worldwide, and with widespread trade and travel, resistance can spread quickly, posing a serious threat to all countries. For Canada, the implications of AMR are stark. When Antibiotics Fail examines the current impacts of AMR on our healthcare system, projects the future impact on Canada’s GDP, and looks at how widespread resistance will influence the day-to-day lives of Canadians. The report examines these issues through a One Health lens, recognizing the interconnected nature of AMR, from healthcare settings to the environment to the agriculture sector. It is the most comprehensive report to date on the economic impact of AMR in Canada

A Call for Action: The Application of the International Health Regulations to the Global Threat of Antimicrobial Resistance

Stephen Harbarth and colleagues argue that the International Health Regulations (IHR) should be applied to the global health threat of antimicrobial resistance

The Macroeconomic Consequences of Renouncing to Universal Access to Antiretroviral Treatment for HIV in Africa: A Micro-Simulation Model

AIM: Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. METHODS: We used a micro-simulation model based on individuals aged 15-49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an "artificial" ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. RESULTS: Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm(3) CD4 cell counts. CONCLUSION: Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the long term. Renouncing or significantly delaying the achievement of this goal, due to "legitimate" short term budgetary constraints would be a misguided choice

Broadening the infection prevention and control network globally; 2017 Geneva IPC-think tank (part 3).

Background: Healthcare-associated infection (HAI) is a major challenge for patient safety worldwide, and is further complicated by antimicrobial resistance (AMR) due to excessive antimicrobial use in both humans and animals. Existing infection prevention and control (IPC) networks must be strengthened and adapted to better address the global challenges presented by emerging AMR. Methods: In June 2017, 42 international experts convened in Geneva, Switzerland, to discuss two key areas for strengthening the global IPC network: 1) broadening collaboration in IPC; and 2) how to bring the fields IPC and AMR control together. Results: The US Centers for Disease Prevention and Control, the European Centre for Disease Prevention and Control, and the World Health Organization (WHO) convened together with international experts to discuss collaboration and networks, demonstrating the participating organizations' commitment to close collaboration in IPC. The challenge of emerging AMR can only be addressed by strengthening this collaboration across international organisations and between public health and academia. The WHO SAVE LIVES: Clean Your Hands initiative is an example of a successful collaboration between multiple global stakeholders including academia and international public health organisations; it can be used as a model. IPC-strategies are included within the four pillars to combat AMR: surveillance, IPC, antimicrobial and diagnostic stewardship, research and development. The prevention of transmission of multidrug-resistant microorganisms is a patient safety issue, and must be strengthened in the fight against AMR. Conclusions: The working group determined that international organisations should take the lead in creating new networks, which will in turn attract academia and other stakeholders to join. At the same time, they should invest in bringing existing IPC and AMR networks under one umbrella. Transmission of multidrug-resistant microorganisms in hospitals and in the community threatens the success of antimicrobial stewardship programmes, and thus, research and development in IPC should be addressed as an enhanced global priority

Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2).

Background: The high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR? Methods: In June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene. Results: Research on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are coupled with reminders for healthcare professionals. Conclusions: The four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best practice in hand hygiene

Towards a New Political Economy of Behavioral Public Policy

The dominant normative framework in behavioral public policy postulates paternalistic intervention to increase individual utility, epitomized by the so-called nudge approach. In this article, an alternative political economy of behavioral public policy is proposed that sits within, or at least closely aside, the liberal economic tradition. In short, rather than impose utility maximization as the normative ideal, this framework proposes that policy makers provide an environment that is conducive to each person's own conception of a flourishing life, while at the same time regulating against behaviorally informed harms and for behaviorally induced, otherwise forgone, benefits

Extracellular signal-regulated kinase 1/2 activity is not required in mammalian cells during late G2 for timely entry into or exit from mitosis

Author Posting. © American Society for Cell Biology, 2006. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 17 (2006): 5227-5240, doi:10.1091/mbc.E06-04-0284.Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be required in mammalian cells for timely entry into and exit from mitosis (i.e., the G2-mitosis [G2/M] and metaphase-anaphase [M/A] transitions). However, it is unclear whether this involvement reflects a direct requirement for ERK1/2 activity during these transitions or for activating gene transcription programs at earlier stages of the cell cycle. To examine these possibilities, we followed live cells in which ERK1/2 activity was inhibited through late G2 and mitosis. We find that acute inhibition of ERK1/2 during late G2 and through mitosis does not affect the timing of the G2/M or M/A transitions in normal or transformed human cells, nor does it impede spindle assembly, inactivate the p38 stress-activated checkpoint during late G2 or the spindle assembly checkpoint during mitosis. Using CENP-F as a marker for progress through G2, we also show that sustained inhibition of ERK1/2 transiently delays the cell cycle in early/mid-G2 via a p53-dependent mechanism. Together, our data reveal that ERK1/2 activity is required in early G2 for a timely entry into mitosis but that it does not directly regulate cell cycle progression from late G2 through mitosis in normal or transformed mammalian cells.This research was supported by National Institutes of Health Grant GMS-40198 to C.L.R., by National Institutes of Health/National Cancer Institute Grant CA109182, and Samuel Waxman Cancer Research Foundation grants to J.A.A.-G

Kinetochore fiber formation in animal somatic cells : dueling mechanisms come to a draw

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosoma 114 (2005): 310-318, doi:10.1007/s00412-005-0028-2.The attachment to and movement of a chromosome on the mitotic spindle is mediated by the formation of a bundle of microtubules (MTs) that tethers the kinetochore on the chromosome to a spindle pole. The origin of these “kinetochore fibers” (K-fibers) has been investigated for over 125 years. As noted in 1944 by Schrader, there are only three possible ways to form a K-fiber: either it a) grows from the pole until it contacts the kinetochore; b) grows directly from the kinetochore; or c) it forms as a result of an interaction between the pole and the chromosome. Since Schrader’s time it has been firmly established that K-fibers in centrosome-containing animal somatic cells form as kinetochores capture MTs growing from the spindle pole (route a). It is now similarly clear that in cells lacking centrosomes, including plants and many animal oocytes, K-fibers “self-assemble” from MTs generated by the chromosomes (route b). Can animal somatic cells form K-fibers in the absence of centrosomes by the “self-assembly” pathway? In 2000 the answer to this question was shown to be a resounding “yes”. With this result, the next question became whether the presence of a centrosome normally suppresses K-fiber self-assembly, or if this route works concurrently with centrosome-mediated K-fiber formation. This question, too, has recently been answered: observations on untreated live animal cells expressing GFP-tagged tubulin clearly show that kinetochores can nucleate the formation of their associated MTs in the presence of functional centrosomes. The concurrent operation of these two “dueling” routes for forming K-fibers in animals helps explain why the attachment of kinetochores and the maturation of K-fibers occur as quickly as it does on all chromosomes within a cell.The work is sponsored by NIH grant GMS 40198