The battle against fungi:lessons in antifungal stewardship from COVID 19 times

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).</p

Essential and Forgotten antibiotics:an inventory in low- and middle-income countries

Background: The World Health Organization Essential Medicines List (WHO-EML) includes ‘access’ antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of ‘forgotten’ antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications. Objective: To investigate which WHO-EML ‘access’ and ‘forgotten’ antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs). Methods: The Scientific Committee used a consensus procedure to select 26 WHO-EML ‘access’ and 15 ‘forgotten’ antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market. Results: Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML ‘access’ antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 ‘access’ antibiotics were approved in more than two-thirds of countries. Among the 15 ‘forgotten’ antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23–35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries. Conclusions: WHO-EML ‘access’ antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the ‘forgotten’ antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria

1 - Introducción

At the end of 2019, a new zoonotic coronavirus originated in China, which was called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). This virus first generated the denomination by the World Health Organization (WHO) of a Public Health Emergency of International Concern (PHEIC), and later of pandemic. The impact of this COVID-19 pandemic has affected the entire world. Latin America has not been the exception, and with this this Consensus, which brings together the work of experts from different countries in the region, gathered in the Pan American Association of Infectious Diseases (API), seeks to serve as a guide, especially for those countries in which to date have not developed clear guidelines, especially in the diagnosis and treatment of the disease, but also in other epidemiological and preventive aspects. This consensus is divided into parts. This one, corresponds to the first, Introduction.A finales del año 2019 se originó en China un nuevo coronavirus, zoonótico, que fue denominado como el coronavirus del síndrome agudo respiratorio severo 2 (SARS-CoV-2), causante de la enfermedad por coronavirus 2019 (COVID-19). Este virus generó inicialmente la denominación por parte de la Organización Mundial de la Salud (OMS) de Emergencia Sanitaria de Preocupación Internacional (ESPI), y posteriormente de pandemia. El impacto de esta pandemia por COVID-19 ha afectado todo el mundo. América Latina no ha sido la excepción, y con ello el presente Consenso, que reúne el trabajo de expertos de diferentes países de la región, congregados en la Asociación Panamericana de Infectología (API), busca servir de guía, especialmente para aquellos países en los cuales no se han desarrollado a la fecha lineamientos claros, especialmente en el diagnóstico y tratamiento de la enfermedad, pero también en otros aspectos epidemiológicos y preventivos. El presente consenso está dividido en partes. Esta, corresponde a la primera, Introducción

1 - Introducción

At the end of 2019, a new zoonotic coronavirus originated in China, which was called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). This virus first generated the denomination by the World Health Organization (WHO) of a Public Health Emergency of International Concern (PHEIC), and later of pandemic. The impact of this COVID-19 pandemic has affected the entire world. Latin America has not been the exception, and with this this Consensus, which brings together the work of experts from different countries in the region, gathered in the Pan American Association of Infectious Diseases (API), seeks to serve as a guide, especially for those countries in which to date have not developed clear guidelines, especially in the diagnosis and treatment of the disease, but also in other epidemiological and preventive aspects. This consensus is divided into parts. This one, corresponds to the first, Introduction.A finales del año 2019 se originó en China un nuevo coronavirus, zoonótico, que fue denominado como el coronavirus del síndrome agudo respiratorio severo 2 (SARS-CoV-2), causante de la enfermedad por coronavirus 2019 (COVID-19). Este virus generó inicialmente la denominación por parte de la Organización Mundial de la Salud (OMS) de Emergencia Sanitaria de Preocupación Internacional (ESPI), y posteriormente de pandemia. El impacto de esta pandemia por COVID-19 ha afectado todo el mundo. América Latina no ha sido la excepción, y con ello el presente Consenso, que reúne el trabajo de expertos de diferentes países de la región, congregados en la Asociación Panamericana de Infectología (API), busca servir de guía, especialmente para aquellos países en los cuales no se han desarrollado a la fecha lineamientos claros, especialmente en el diagnóstico y tratamiento de la enfermedad, pero también en otros aspectos epidemiológicos y preventivos. El presente consenso está dividido en partes. Esta, corresponde a la primera, Introducción

Macro level influences on strategic responses to the COVID-19 pandemic – an international survey and tool for national assessments

Background Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. Methods A cross-sectional electronic survey of health and non-health care professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains – Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. Results 928 respondents from 66 countries (57% health care professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Conclusions The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling

Clinical management of severe infections caused by carbapenem-resistant Gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations.

OBJECTIVES: Optimal treatment of carbapenem-resistant Gram-negative (CR-GNB) infections is uncertain due to the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. METHODS: A 36-items-questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball-sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. RESULTS: 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in High-Income-Countries vs 59% (194/283) in Upper-Medium-Income-Countries and 30% (118/196) in Lower-Middle-Income-Countries/Lower-Income-Countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) of in vitro-synergism. CONCLUSIONS: Management of CR-GNB infections is far from being standardized. Strategic public health focussed randomised controlled trials are urgently required to inform evidence-based treatment guidelines

A one health framework to estimate the cost of antimicrobial resistance

Abstract Objectives/purpose The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level. Methods GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level. Results The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies. Conclusion In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C