Panel stacking is a threat to consensus statement validity.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Whole genomes from bacteria collected at diagnostic units around the world 2020.

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Restricting access to antibiotics: The effectiveness of a 'no repeats' government policy intervention.

BACKGROUND: Australia has a high rate of antibiotic use. Government policy interventions are one strategy to optimise the use of antibiotics. On 1 April 2020, the Australian Government Department of Health introduced a policy intervention to increase the quality use of four antibiotics. OBJECTIVES: To assess if the government policy intervention improved the appropriate supply of the four antibiotics amoxicillin, amoxicillin-clavulanic acid, cefalexin and roxithromycin. METHOD: This study employed a retrospective cohort study design comparing a 10% sample (n = 345,018) of four antibiotics prescribed and dispensed in Australia during a three-month period (May, June, July) in 2019, and again in 2020 (after the policy intervention). The 10% sample of PBS data was obtained from the Australian Government Department of Health. Descriptive statistics, bivariate and multivariable logistic regression analysis were carried out. RESULTS: The results suggest the policy change improved the appropriate supply of original prescriptions in 2020 compared to 2019 OR = 1.75 (95% CI = 1.68-1.82, p < 0.001), and appropriate supply of repeat prescriptions OR = 1.56 (95% CI = 1.25-1.96, p < 0.001). In 2020, the proportion of appropriate supply of original prescriptions increased by an absolute difference of 1.8% (95% CI = 1.6-1.9%; P < 0.001), and appropriate supply of repeat prescriptions increased by 3.9% (95% CI = 2.2-5.5%; P < 0.001). The total number of antibiotic prescriptions prescribed and dispensed in 2019 (N = 219,960) reduced in 2020 (N = 125,058) after the policy intervention. CONCLUSION: The study provides evidence for the impact of a government policy intervention to improve the appropriate supply of antibiotics, although some of the reduction in antibiotic use was likely due to the concomitant COVID-19 pandemic. Further research is required to assess the impact of the intervention outside a pandemic.

An Old Defence Against New Infections: The Open-Air Factor and COVID-19.

Outdoors, the risks of transmission of COVID-19 and many other respiratory infections are low. Several environmental factors are known to reduce the viability of viruses and other infectious pathogens in the air. They include variations in temperature, relative humidity, solar ultraviolet radiation, and dilution effects. But one agent that reduces the viability of both viruses and bacteria outdoors, the germicidal open-air factor (OAF), has not been properly recognized for decades. This is despite robust evidence that the OAF can influence both the survival of airborne pathogens and the course of infections. The germicidal effects of outdoor air were widely exploited during the late 19th and early 20th centuries. Firstly, in the treatment of tuberculosis patients who underwent 'open-air therapy' in sanatoria; and secondly by military surgeons during the First World War. They used the same open-air regimen in specially designed hospital wards to disinfect and heal severe wounds among injured soldiers. It was also used on influenza patients during the 1918-19 pandemic. Later, in the 1950s, open-air disinfection and treatment of burns were proposed in the event of nuclear warfare. During the 1960s, the OAF briefly returned to prominence when biodefence scientists conducted experiments proving that open air has a potent germicidal effect. When this work ended in the 1970s, interest in the OAF again fell away, and it remains largely ignored. The COVID-19 pandemic has revived interest in understanding the transmission dynamics and survival of viruses in the air. The pandemic has also stimulated research in the science and practice of improved ventilation to control respiratory infections. Such work is incomplete without an appreciation of the inactivation of viruses and other pathogens by the OAF, but this needs further investigation as a matter of urgency. Research to better understand the conditions under which the OAF can be preserved indoors is urgently needed. We need to review building design with better regard to infection control and patient recovery. But we need to act without delay, as there is already sufficient evidence to show that public health generally would improve if more emphasis was placed on increased exposure to outdoor air.

The effect of eye protection on SARS-CoV-2 transmission: a systematic review.

BACKGROUND: The effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2. METHODS: We searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2. RESULTS: We screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, goggles, and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case-control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low. CONCLUSIONS: Current studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.

Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

COVID-19 and future pandemics: is isolation and social distancing the new norm?

The coronavirus, named SARS-CoV-2, is the cause of COVID-19. This virus spreads readily from person to person and predominantly to and from the respiratory route and through droplets. There are many different interventions that can be and are used to decrease successfully the risk and spread of COVID-19. Most of the principles underpinning these interventions relate to isolation and social distancing. These will need to be continued, at least in part, until safe and very effective vaccines become widely available and are delivered extensively and successfully globally. This new norm is isolation, plus social and physical distancing, and this new norm will likely be with us for some time to come. It will also be with us in any future pandemics, whether caused by bacteria or viruses, but especially when the causative pathogen spreads predominantly through the respiratory route. However, lockdowns and restrictions also cause many adverse but unintended economic, social and health consequences. Therefore, what is put into place needs to be proportionate to levels of risk of disease as well as spread, and which will vary in different localities and with time.

Identification and characterisation of fosfomycin resistance in Escherichia coli urinary tract infection isolates from Australia.

Of 1033 Escherichia coli urinary tract infection isolates collected from females >12 years of age in Australia in 2019, only 2 isolates were resistant to fosfomycin with a minimum inhibitory concentration (MIC) of >256 mg/L. Despite having different multilocus sequence types, the two isolates harboured an identical plasmid-encoded fosA4 gene. The fosA4 gene has previously been identified in a single clinical E. coli isolate cultured in Japan in 2014. Each fosfomycin-resistant isolate harboured two conjugative plasmids that possessed an array of genes conferring resistance to aminoglycosides, ß-lactams, macrolides, quinolones, sulfonamides and/or trimethoprim.

Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey.

BACKGROUND: Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI. METHODS: The study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog. RESULTS: In total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2-64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2-99.2%) and non-HCWs (80%-96.5%) would work with "minor" ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite. CONCLUSION: A future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine.

CON: COVID-19 will not result in increased antimicrobial resistance prevalence.

Antimicrobial resistance (AMR) is affected by many factors, but too much of our focus has been on antimicrobial usage. The major factor that drives resistance rates globally is spread. The COVID-19 pandemic should lead to improved infection prevention and control practices, both in healthcare facilities and the community. COVID-19 will also have ongoing and profound effects on local, national and international travel. All these factors should lead to a decrease in the spread of resistant bacteria. So overall, COVID-19 should lead to a fall in resistance rates seen in many countries. For this debate we show why, overall, COVID-19 will not result in increased AMR prevalence. But globally, changes in AMR rates will not be uniform. In wealthier and developed countries, resistance rates will likely decrease, but in many other countries there are already too many factors associated with poor controls on the spread of bacteria and viruses (e.g. poor water and sanitation, poor public health, corrupt government, inadequate housing, etc.). In these countries, if economies and governance deteriorate further, we might see even more transmission of resistant bacteria.

Risk factors for acquisition of multidrug-resistant Enterobacterales among international travellers: a synthesis of cumulative evidence.

BACKGROUND: Recent studies have shown that over 50% of people travelling to Southeast Asia return colonized with multidrug-resistant Enterobacterales (MRE) including carbapenemase-producing Enterobacterales. Importation of MRE by travellers and subsequent spread to family members, communities and healthcare facilities poses real risks that have not yet been adequately assessed. This systematic review and meta-analysis aims to quantify the risk factors and interventions for reducing the risk of MRE acquisition among international travellers. METHODS: A systematic search was conducted in PubMed, Web of Science and Scopus for analytical epidemiological studies containing data post-2000 that assessed the risk factors to acquire and/or interventions to reduce the risk of MRE acquisition in travellers. Two researchers independently screened all the studies and extracted the information, and disagreements were resolved through consensus. The proportions of MRE acquisition by the region of destination and the odds ratio (OR) for the different risk factors and/or interventions were pooled using the inverse variance heterogeneity model. RESULTS: A total of 20 studies (5253 travellers from high-income countries) were included in the meta-analysis. South Asia [58.7%; 95% confidence interval (CI), 44.5-72.5%] and Northern Africa (43.9%; 95% CI 37.6-50.3%) were the travel destinations with the highest proportion of MRE acquisition. Inflammatory bowel disease (OR 2.1; 95% CI 1.2-3.8), use of antibiotics (OR 2.4; 95% CI 1.9-3.0), traveller's diarrhoea (OR 1.7; 95% CI 1.3-2.3) and contact with the healthcare system overseas (OR 1.5; 95% CI 1.1-2.2) were associated with MRE colonization. Vegetarians (OR 1.4; 95% CI 1.0-2.0) and backpackers (OR 1.5; 95% CI 1.2-1.8) were also at increased odds of MRE colonization. Few studies (n = 6) investigated preventive measures and found that consuming only bottled water/beverages, meticulous hand hygiene and probiotics had no protective effect on MRE colonization. CONCLUSIONS: International travel is an important driver for MRE spread worldwide. Future research needs to identify effective interventions to reduce the risk of MRE acquisition as well as design strategies to reduce local transmission on return.