H5N1

Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Via The Lancet: Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. This is very disturbing, because it's probably an underestimate. Excerpt from the long summary:

In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. 

For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). 

Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. 

Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. 

Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. 

Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths.

WHO: Antimicrobial Resistance, Hypervirulent Klebsiella pneumoniae - Global situation

A WHO Disease Outbreak News report: Antimicrobial Resistance, Hypervirulent Klebsiella pneumoniae - Global situation. Excerpt:

Situation at a glance

In early 2024, the Global Antimicrobial Resistance and Surveillance System on Emerging Antimicrobial Resistance Reporting (GLASS-EAR) issued a request for information to assess the current global situation given the increased identification of isolates of hypervirulent Klebsiella pneumoniae (hvKp) sequence type (ST) 23 carrying resistant genes to the carbapenem antibiotics – carbapenemase genes. 

K. pneumoniae strains that can cause severe infections in healthy individuals and have been identified with increasing frequency in recent years are considered hypervirulent compared to classical strains because of their ability to infect both healthy and immunocompromised individuals and because of their increased tendency to produce invasive infections.The presence of hvKp ST23 was reported in at least one country in all six WHO Regions. 

The emergence of these isolates with resistance to last-line antibiotics like carbapenems necessitates the administration of alternative antimicrobial treatment, which may not be available in many contexts. 

WHO recommends that Member States progressively increase their laboratory diagnostic capacity to allow for the early and reliable identification of hvKp, as well as reinforce laboratory capacities in molecular testing and detection and analyses of relevant virulence genes in addition to resistance genes. 

The assessment of risk at the global level is moderate given the challenges with surveillance, lack of information on laboratory testing rates, track and scale of community transmission, the gap in the available data on infections, hospitalization, and the overall burden of the disease.

Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis

Via The Lancet: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The summary:

Background  

Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.  

Methods  

We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. 

Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. 

Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level.   

Findings         

On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. 

The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.  

Interpretation  

To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat.

With all eyes on Covid-19, drug-resistant infections crept in

Via The New York Times: With All Eyes on Covid-19, Drug-Resistant Infections Crept In.

As Covid-19 took hold over the last year, hospitals and nursing homes used and reused scarce protective equipment — masks, gloves, gowns. This desperate frugality helped prevent the airborne transfer of the virus. 

But it also appears to have helped spread a different set of germs — drug-resistant bacteria and fungi — that have used the chaos of the pandemic to grow opportunistically in health care settings around the globe. 

These bacteria and fungi, like Covid-19, prey on older people, the infirm and those with compromised immune systems. They can cling tenaciously to clothing and medical equipment, which is why nursing homes and hospitals before the pandemic were increasingly focused on cleaning rooms and changing gowns to prevent their spread. 

That emphasis all but slipped away amid an all-consuming focus on the coronavirus. In fact, experts warn, the changes in hygiene and other practices caused by the Covid-19 fight are likely to have contributed to the spread of these drug-resistant germs.  

“Seeing the world as a one-pathogen world is really problematic,” said Dr. Susan S. Huang, an infectious disease specialist at the University of California at Irvine Medical School, noting that the nearly singular focus on the pandemic appears to have led to more spread of drug-resistant infection. “We have every reason to believe the problem has gotten worse.”  

A few data points reinforce her fears, including isolated outbreaks of various drug-resistant infections in Florida, New Jersey and California, as well as in India, Italy, Peru and France. Overall figures have been hard to track because many nursing homes and hospitals simply stopped screening for the germs as resources were diverted to Covid-19.  

When even modest screening picked up again early in the summer, the results suggested that certain drug-resistant organisms had taken root and spread. Particularly troublesome have been growing case counts of a fungus called Candida auris, which authorities had tried to fight before the pandemic with increased screening, isolation of infected patients and better hygiene.

BC’s top doctor wrote a book about fighting viruses in 2009

The Tyee has published my article: BC’s Top Doctor Wrote a Book about Fighting Viruses in 2009. Excerpt:

Soap and Water & Common Sense: The Definitive Guide to Viruses, Bacteria, Parasites, and Disease By Dr. Bonnie Henry House of Anansi, 2009. 

Dr. Bonnie Henry’s news conferences have become a part of daily life in B.C. When they attend her briefings, Premier John Horgan, Health Minister Adrian Dix, and Public Safety Minister Mike Farnworth fade into the background, at a safe distance from her and one another. They speak chiefly to endorse what their chief medical officer says. The contrast with Trump’s press conferences is impossible to miss. 

It certainly helps that Dr. Henry can deliver alarming news in a calm tone of voice, without relying on technical jargon; we pay attention, we absorb the news, but we don’t freak out. Treated like adults, we respond like adults.  

Those same communication skills are evident throughout her 2009 book Soap and Water & Common Sense, written years before she became B.C.’s provincial health officer. The book is now available with a new introduction, written in March, and the content itself is still very timely: while our healthcare system is fighting COVID-19, other diseases are going to exploit their opportunity.

Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019

A rapid communication to Eurosurveillance: Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. The abstract:

From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.

ECDC: Surveillance of antimicrobial resistance in Europe 2018

ECDC has published Surveillance of antimicrobial resistance in Europe 2018. Excerpt from the executive summary: 

As in previous years, the AMR situation in Europe displays wide variations depending on bacterial species, antimicrobial group and geographical region. For several bacterial species–antimicrobial group combinations, a north-to-south and west-to-east gradient is evident. In general, lower resistance percentages were reported by countries in the north while higher percentages were reported in the south and east of Europe. The high variability in AMR across EU/EEA countries reinforces the scope for significant reductions through investments to strengthen current best practice.   

In 2018, more than half of the Escherichia  coli isolates reported to EARS-Net and more than a third of the Klebsiella pneumoniae isolates were resistant to at least one antimicrobial group under regular surveillance, and combined resistance to several antimicrobial groups was frequent. Resistance percentages were generally higher in K. pneumoniae than in E. coli. While carbapenem resistance remained rare in E. coli, several countries reported carbapenem resistance percentages above 10% for K. pneumoniae. 

Carbapenem resistance was also common in Pseudomonas  aeruginosa and Acinetobacter species, and at higher percentages compared with K. pneumoniae. For all four gram-negative bacteria, the countries reporting the highest carbapenem resistance percentages were also among the countries reporting the highest resistance percentages for other antimicrobial groups. For most gram-negative bacterial species–antimicrobial group combinations, changes in resistance percentages between 2015 and 2018 were moderate, and resistance remained at previously reported high levels.  

For Streptococcus pneumoniae, the resistance situation appeared stable, but with large inter-country variations. For Staphylococcus aureus, the decline in the percentage of methicillin-resistant (i.e. MRSA) isolates reported in previous years continued in 2018. Nevertheless, MRSA remains an important pathogen in the EU/EEA, as the levels of MRSA were still high in several countries, and combined resistance to other antimicrobial groups was common. 

Drug resistance likely to kill 400,000 Canadians by 2050, report predicts

Via CBC: Drug resistance likely to kill 400,000 Canadians by 2050, report predicts. Excerpt:

Superbugs are likely to kill nearly 400,000 Canadians and cost the economy about $400 billion in gross domestic product over the next 30 years, warns a landmark report. 

An expert panel cautions in "When antibiotics fail: The growing cost of antimicrobial resistance in Canada" that the percentage of bacterial infections resistant to treatment is likely to grow from 26 per cent in 2018 to 40 per cent by 2050.

This increase is expected to cost Canada 396,000 lives, $120 billion in hospital expenses and $388 billion in gross domestic product over the next three decades. 

"This is almost as big, if not bigger, than climate change in a sense because this is directly impacting people. The numbers are just staggering," Brett Finlay, a University of British Columbia microbiology professor who chaired the panel, said in an interview. "It's time to do something now."  

The Public Health Agency of Canada commissioned the report on the socio-economic impacts of antimicrobial resistance and the Council of Canadian Academies assembled the independent panel. The 268-page document released Tuesday represents the most comprehensive picture to date of the country's resistance rate, as well as its costs to the health system and economy.

Antimicrobial resistance occurs when micro-organisms, including bacteria, viruses and fungi, evolve to resist the drugs that would otherwise kill them. Unnecessary antimicrobial use in humans and agriculture exacerbates the problem, and widespread international travel and trade help resistant bacteria spread around the world. 

The most common antimicrobials are antibiotics, which treat infections caused by bacteria. The report focuses on resistant bacteria, but uses the broader term antimicrobial because surveillance data tend to be collected under this heading.  

Canada slow to act 

An investigation by The Canadian Press last year revealed Canada has been sluggish to act on the growing threat. At that time, the government did not know how many Canadians were dying of resistant infections and it had not produced a plan that lays out responsibilities for provinces and territories.  

A pan-Canadian action plan has still not materialized, but the new report estimates an annual death toll in Canada. The panel used the current resistance rate of 26 per cent to calculate resistant infections contributed to over 14,000 deaths in 2018, and of those, 5,400 were directly attributable to the infections — only slightly less than those caused by Alzheimer's disease. 

The panel's economists used a more cautious model to project the impacts than a well-known international report by British economist Jim O'Neill, which predicted up to 10 million global deaths annually by 2050.

The Canadian report's findings on the economic and social toll of antimicrobial resistance are stark. Currently, the problem costs the national health-care system $1.4 billion a year, and by 2050, that figure is projected to grow to $7.6 billion, the report says. The cost to GDP is expected to jump from $2 billion to up to $21 billion annually.

International travel as source of a hospital outbreak with an unusual methicillin-resistant Staphylococcus aureus clonal complex 398, Denmark, 2016

Eurosurveillance has published International travel as source of a hospital outbreak with an unusual meticillin-resistant Staphylococcus aureus clonal complex 398, Denmark, 2016. The abstract:

In May 2016, an unusual outbreak with the Panton-Valentine leukocidin-positive human variant of methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 occurred among mothers and infants in the maternity unit of a Danish hospital. MRSA sharing genotypic and phenotypic characteristics was confirmed in 36 cases, including 26 patients, nine household members and a healthcare worker (HCW) who had contact with all the patients. The national MRSA database contained 37 seemingly unlinked MRSA cases whose isolates shared the same genotypic and phenotypic characteristics as the outbreak strain. 

Whole genome sequencing showed that three of these isolates clustered together with the 36 outbreak isolates, suggesting spread outside the hospital. The HCW and 21 of 37 cases from the national MRSA database had links to south-eastern Asia, where the outbreak strain is endemic. These findings suggest that the HCW acquired the outbreak strain while travelling in south-eastern Asia and then introduced it into the hospital; from there, it spread within the patients’ households and into the community. 

Screening of travellers returning from countries with high levels of MRSA could be an important intervention to prevent spread of these bacteria into hospitals via patients or HCWs.

ECDC: Response plan to control and manage the threat of multi- and extensively drug-resistant gonorrhoea in Europe

ECDC has published Response plan to control and manage the threat of multi- and extensively drug-resistant gonorrhoea in Europe. The executive summary:

Gonorrhoea is the second most notified sexually transmitted infection in the European Union and European Economic Area (EU/EEA) after chlamydia. The overall trend between 2008-2017 among 20 of the 28 EU/EEA countries consistently reporting, showed an increase in the number of notified gonorrhoea cases. In addition, over the past decades, Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to several antimicrobial classes. 

Six years after the initial ECDC Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe, the threat of untreatable gonorrhoea remains. ECDC reviewed the response plan and the 2019 update strives to further support EU Member States to develop and implement national strategies and interventions to control the threat of multidrug-resistant and extensively drug-resistant gonorrhoea in a multidisciplinary approach by outlining the suggested public health response to this threat with several vital components. 

Preventing the emergence and spread of AMR in N. gonorrhoeae is just one aspect of gonorrhoea control: as part of comprehensive management strategies including appropriate treatment, diagnostics and testing algorithms (e.g., three-site testing in men who have sex with men), test of cure, notification and treatment of partners, enhanced focus on risk groups and STI prevention measures, including advocating for increased condom use.