H5N1

WHO: New report calls for urgent action to avert antimicrobial resistance crisis

A news release: New report calls for urgent action to avert antimicrobial resistance crisis. Excerpt:

UN, international agencies and experts today released a groundbreaking report demanding immediate, coordinated and ambitious action to avert a potentially disastrous drug-resistance crisis.   

If no action is taken - warns the UN Ad hoc Interagency Coordinating Group on Antimicrobial Resistance who released the report – drug-resistant diseases could cause 10 million deaths each year by 2050 and damage to the economy as catastrophic as the 2008-2009 global financial crisis. By 2030, antimicrobial resistance could force up to 24 million people into extreme poverty.    

Currently, at least 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis. More and more common diseases, including respiratory tract infections, sexually transmitted infections and urinary tract infections, are untreatable; lifesaving medical procedures are becoming much riskier, and our food systems are increasingly precarious.    

The world is already feeling the economic and health consequences as crucial medicines become ineffective. Without investment from countries in all income brackets, future generations will face the disastrous impacts of uncontrolled antimicrobial resistance.   

Recognizing that human, animal, food and environmental health are closely interconnected, the report calls for a coordinated, multisectoral “One Health” approach.    

It recommends countries:  

• prioritize national action plans to scale-up financing and capacity-building efforts; 

•  put in place stronger regulatory systems and support awareness programs for responsible and prudent use of antimicrobials by professionals in human, animal and plant health; 

• invest in ambitious research and development for new technologies to combat antimicrobial resistance; 

• urgently phase out the use of critically important antimicrobials as growth promoters in agriculture.

See also this report in The Guardian.

Finnish researchers use CRISPR gene editing to fight antibiotic resistance in bacteria

Via Yle Uutiset: Finnish researchers use CRISPR gene editing to fight antibiotic resistance in bacteria.

Scientists at the University of Jyväskylä have developed bacteria that spread a genetic mutation which can destroy microorganisms' ability to be antibiotic-resistant.  

The research group headed by academy research fellow Matti Jalasvuori aims to develop probiotic bacteria that re-sensitise already resistant bacteria to antibiotics. 

According to Jalasvuori there are two ways that bacteria become resistant: either through the use of antibiotics or through the exchange of resistant genes between bacteria. The latter is possible even if the bacteria have not been exposed to antibiotics.  

"Especially among notorious hospital pathogens, such as E. coli and K. pneumoniae, resistance genes are usually a part of mobile genetic elements that readily transfer from one bacterium to another", said Jalasvuori.  

This gene transfer, however, can also be turned against bacteria. Jalasvuori’s group has developed modified bacteria that disseminate DNA-sequences called CRISPR-elements, which in turn destroy resistance genes in bacterial cells.  

CRISPR-elements can be transferred into, for example, gut flora with harmless probiotic bacteria.  

“In the future, this approach could help prevent antibiotic-resistant bacteria from accumulating in certain environments, such as farms,” Jalasvuori added.  

Jane and Aatos Erkko Foundation has awarded the research group a grant worth 255,000 euros for investigating the transfer of such elements.  

It was reported last month that thousands of people in Finland are diagnosed yearly with urinary tract infections caused by drug-resistant E. coli bacteria.

The scary shortage of infectious-disease doctors

Via The New York Times, an op-ed: The Scary Shortage of Infectious-Disease Doctors. Is this also true of countries with reasonable health-insurance systems? Excerpt:

Many have heard of the rise of drug-resistant infections. But few know about an issue that’s making this threat even scarier in the United States: the shortage of specialists capable of diagnosing and treating those infections. 

Infectious diseases is one of just two medicine subspecialties that routinely do not fill all of their training spots every year in the National Resident Matching Program (the other is nephrology). Between 2009 and 2017, the number of programs filling all of their adult-infectious-disease training positions dropped by more than 40 percent. 

This could not be happening at a worse time. Antibiotic-resistant microbes, known as superbugs, are pinballing around the world, killing hundreds of thousands of people every year. The Times recently reported on Candida auris, a deadly new fungus that has infected hospital patients in Illinois, New Jersey and New York. 

Everyone who works in health care agrees that we need more infectious-disease doctors, yet very few actually want the job. What’s going on?  

The problem is that infectious-disease specialists care for some of the most complicated patients in the health care system, yet they are among the lowest paid. It is one of the only specialties in medicine that sometimes pays worse than being a general practitioner. At many medical centers, a board-certified internist accepts a pay cut of 30 percent to 40 percent to become an infectious-disease specialist. 

 This has to do with the way our insurance system reimburses doctors. Medicare assigns relative value units to the thousands of services that doctors provide, and these units largely determine how much physicians are paid. The formula prioritizes invasive procedures over intellectual expertise.

The problem is that infectious-disease doctors don’t really do procedures. It is a cognitive specialty, providing expert consultation, and insurance doesn’t pay much for that. 

For example, I recently diagnosed a case of fungal pneumonia. To arrive at this diagnosis took hours: first, speaking with the patient’s primary care doctor and pulmonologist, followed by a long stretch reviewing chest X-rays and other imaging studies with a radiologist, before examining the cells in the patient’s lung tissue under a microscope to confirm the diagnosis and report back to the anxious patient and family. Most of this work was done free. 

A generation ago, most well-rounded doctors knew what to do when a patient developed a fever. Not anymore. New threats like Candida auris pop up all the time, and to identify a deadly pathogen, we often have to use a sophisticated technique called matrix-assisted laser desorption ionization time-of-flight mass spectrometry. As the name suggests, it requires a bit of expertise.

Back in the day, there were only a handful of reliable antibiotics to choose from. But as more bugs have emerged, and more have become resistant to standard treatments, we’ve had to develop new drugs to fight them. The good news is that in 2018, the Food and Drug Administration approved a cadre of new antibiotics to confront the rising threat of superbugs, including eravacycline, plazomicin and omadacycline, and we can expect even more this year. But very few physicians know how to use these powerful new drugs. Many don’t even know how to pronounce them.  

Infectious-disease specialists are often the only health care providers in a hospital — or an entire town — who know when to use all of the new antibiotics (and when to withhold them). These experts serve as an indispensable cog in the health care machine, but if trends continue, we won’t have enough of them to go around. 

The terrifying part is that most patients won’t even know about the deficit. Your doctor won’t ask a specialist for help because in some parts of the country, the service simply won’t be available. She’ll just have to wing it.

Culture of secrecy shields hospitals with outbreaks of drug-resistant infections

Via The New York Times: Culture of Secrecy Shields Hospitals With Outbreaks of Drug-Resistant Infections. Excerpt from a disturbing report:

In January, the Centers for Disease Control and Prevention sent out an urgent public alert about a deadly bacteria, resistant to virtually every known antibiotic, that sickened more than a dozen Americans who had elective surgery at Grand View Hospital in Tijuana, Mexico. 

But when similar outbreaks take place at hospitals on American soil, the C.D.C. makes no such public announcement. That is because under its agreement with states, the C.D.C. is barred from publicly identifying hospitals that are battling to contain the spread of dangerous pathogens.  

The rise of a deadly drug-resistant fungus called Candida auris, a focus of a New York Times report last weekend, has raised fresh questions about the secrecy enveloping infectious outbreaks at American medical institutions.

Patient advocates say hospitals and health authorities are often slow to alert the public about drug-resistant germs, potentially endangering patients. 

“They might not get up and go to another hospital, but patients and their families have the right to know when they are at a hospital where an outbreak is occurring,” said Lisa McGiffert of the Patient Safety Action Network. “That said, if you’re going to have hip replacement surgery, you may chose to go elsewhere.” 

Kevin Kavanagh, board chairman of the advocacy group Health Watch USA, contrasted the C.D.C.’s handling of the infections in Tijuana with a 2016 outbreak of a different drug-resistant pathogen, known as carbapenem-resistant Enterobacteriaceae, or CRE, at a rural hospital in Kentucky. It was not until early 2018 that the C.D.C. issued a report on that outbreak — and even then, the agency did not name the hospital where it occurred.  

CRE sometimes kills up to half of people infected. No deaths were reported in the Kentucky outbreak, but at least two dozen patients at the hospital were colonized with the bug, meaning they were not sick but could have spread it to others.

The report identified a cleaning cart as a possible source for the spread of the pathogen, which had traveled between the hospital’s emergency room and its surgical ward. 

The C.D.C. declined to comment, but in the past officials have said their approach to confidentiality is necessary to encourage the cooperation of hospitals and nursing homes, which might otherwise seek to conceal infectious outbreaks.  

Those pushing for increased transparency say they are up against powerful medical institutions eager to protect their reputations, as well as state health officials who also shield hospitals from public scrutiny.

ECDC country visit to Norway to discuss antimicrobial resistance issues

ECDC has published ECDC country visit to Norway to discuss antimicrobial resistance issues. The summary:

An ECDC country visit team conducted an assessment mission during the period 12–16 March 2018 to discuss antimicrobial resistance (AMR) issues in Norway. The overall objective of the mission was to provide an observation-based assessment of the situation in Norway regarding prevention and control of AMR through prudent use of antibiotics and infection control.

Data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) show that the proportion of AMR in bacteria from bloodstream infections in Norwegian patients is consistently below the EU/EEA average and often among the lowest in Europe. Nevertheless, although considerably below the EU/EEA average, resistance to broad-spectrum antibiotics such as third-generation cephalosporins has been increasing over the past 10 years. This is the result of  emergence of strains that produce an extended-spectrum beta-lactamase (ESBL), combined with increasing consumption of broad-spectrum antibiotics in healthcare.

Antimicrobials in acute and long-term care

An editorial in Eurosurveillance: Antimicrobials in acute and long-term care: a point in time along the way to improved use. Excerpt:

Antimicrobial use is the most important modifiable factor contributing to resistance. One key strategy against antimicrobial resistance that has the potential to improve patient outcomes is to optimise antimicrobial use. Understanding how antimicrobials are being used informs stewardship efforts in acute care, long-term care and outpatient settings. 

In the acute care setting, stewardship programs encompass tracking and reporting aggregate antimicrobial use metrics, such as days of therapy or defined daily doses. Benchmarking use within and across facilities is helpful in identifying where action is needed. Antimicrobial use point prevalence surveys (PPS) complement the aggregate metrics by providing information on patient-level use, such as indication and site of infection during the specified time period. 

This approach is able to reveal more targeted quality improvements and enables comparisons of antimicrobial use at the national, regional or local level. PPS may be particularly useful for resource-limited hospitals and long-term care facilities (LTCF) with restricted capabilities for capturing use data on a continual basis. Since PPS evaluate antimicrobial use during a single time period, they need to be repeated at regular intervals to monitor trends over time. 

On the occasion of the European Antibiotic Awareness Day on 18 November, this issue of Eurosurveillance is dedicated to several studies presenting results from European PPS based on the European Centre for Disease Prevention and Control (ECDC) healthcare-associated infections (HAI) and antimicrobial use protocol for acute care hospitals and the HAI and antimicrobial use protocol for LTCF.

Papua New Guinea is rich in resources but poor in health

Via The New York Times: Papua New Guinea Is Rich in Resources but Poor in Health. Excerpt:

PORT MORESBY, Papua New Guinea — Polio was vanquished by the Pacific nation of Papua New Guinea 18 years ago. Now, as world leaders gather there for the Asia-Pacific Economic Cooperation summit meeting this week, polio has returned — on top of raging drug-resistant epidemics of tuberculosis, malaria and H.I.V., and deadly flash points of preventable diseases like whooping cough and measles.  

All over the country, there are symptoms of a profound public health emergency; young and old are getting sick and dying unnecessarily, while facilities lack basic medicines and equipment. 

Doctors and experts say the unfolding crisis is the realization of their worst fears after years of deterioration and neglect.  

“We were expecting something like this,” Dr. Anup Gurung, a public health specialist with the World Health Organization, said of the polio outbreak at a news conference in the capital, Port Moresby, in September. 

He pointed to the erosion of vaccination rates, which are down to 30 percent in some parts of the country. “It’s like someone lit a paper castle where everything is on fire,” he said. 

Officials in Papua New Guinea hope that hosting the Asia-Pacific Economic Cooperation, or APEC, meeting in Port Moresby will elevate the country’s international profile, but the health crisis has become an embarrassment for a nation with an abundance of gold, copper, silver, oil and gas. 

Public frustration with the summit spending has already led to two national strikes. The collapse of health services has been a focus of the protests. 

The return of polio is a clear indicator of the failures, with Papua New Guinea accounting for 21 of 109 cases found globally this year. 

The Papua New Guinea outbreak is vaccine-derived, which means that weakened live virus excreted by vaccinated children has mutated and escaped into the rapidly increasing unprotected population. Dr. Gurung blamed “the steady breakdown of the health system” for the country’s polio emergency.  

Local and international experts point to three interlinked causes of the country’s health crisis: the collapse of the medical supply chain; changing relations with the country’s biggest aid donor, Australia; and rampant corruption. 

Getting medicines, equipment and other supplies around Papua New Guinea has always been challenging. The country has few roads, formidable geography and a widely dispersed population, with about 80 percent living in rural and remote locations.  

That improved with assistance from Australia, but the Australian government withdrew from the arrangement in protest in 2013 after Papua New Guinea awarded the national medicine supply contract to a local company that Julie Bishop, then the Australian foreign minister, said had no accreditation and “a history of supplying substandard drugs.” 

The company, Borneo Pacific, won the contract — worth 32 million Australian dollars, or $23 million — despite its bid being millions of dollars higher than those of reputable international organizations. At the time, the Medical Society of Papua New Guinea said the deal would “lead to the deaths of many Papua New Guineans.”  

Reports from health facilities across the country indicate those fears have been borne out. (Borneo Pacific did not respond to requests for comment.)

WHO: Countries step up to tackle antimicrobial resistance

WHO has published Countries step up to tackle antimicrobial resistance. Excerpt:

Countries are making significant steps in tackling antimicrobial resistance (AMR), but  serious gaps remain and require  urgent action, according to a report released today by the Food and Agriculture Organization of the United Nations (FAO), World Organisation for Animal Health (OIE) and the World Health Organization (WHO).

The report charts progress in 154 countries and reveals wide discrepancies. Some, including many European countries, have been working on  AMR policies in human and animal sectors for more than 4 decades. Others have only recently started to take action to contain this growing threat. Progress in developing and implementing plans is greater in high-income than low-income countries but all countries have scope for improvement. No country  reports sustained capacity at scale in all areas.  

The report looks at surveillance, education, monitoring and regulating consumption and use of antimicrobials in human health, animal health and production, as well as plants and the environment – as recommended in the Global Action Plan published in 2015. 

Promising findings include 105 countries with a surveillance system in place for reporting drug-resistant infections in human health and 68 countries with a system for tracking consumption of antimicrobials. In addition, 123 countries reported that they have policies to regulate the sale of antimicrobials, including the requirement of a prescription for human use – a key measure to tackle overuse and misuse of antimicrobials. 

But implementation of these policies varies  and unregulated medicines are still available in places such as street markets, with no limits on how they are used. Medicines are very often sold over the counter and no prescription is requested. This puts human and animal health at risk, potentially contributing to the development of antimicrobial resistance. 

The report highlights areas,  particularly in the animal and food sectors, where there is an urgent need for more investment and action. For example, only 64 countries report that they follow FAO-OIE-WHO recommendations to limit the use of critically important antimicrobials for growth promotion in animal production. Of these, 39 are high-income countries, with the majority in WHO’s European Region. 

By contrast, only 3 countries from WHO’s African Region and 7 countries from the WHO Region of the Americas have taken this important step to reduce the emergence of antimicrobial resistance.

Comparative efficacy of treatments for Clostridium difficile infection

Via The Lancet Infectious Diseases: Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis. The abstract:

Background 

Several new treatments for Clostridium difficile infections have been investigated. We aimed to compare and rank treatments for non-multiply recurrent infections with C difficile in adults. 

Methods 

We did a random effects network meta-analysis within a frequentist setting to obtain direct and indirect comparisons of trials. We searched MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for published and unpublished trials from the creation of these databases until June 30, 2017. We included randomised controlled trials of treatments for non-multiply recurrent infections with confirmed C difficile in adults (at least 18 years) that reported both primary cure and recurrence rates, and we used the Cochrane Risk of Bias tool to appraise trial methods. 

For our analysis, we extracted the total numbers of patients with primary cure and recurrence from published and unpublished reports. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhoea minus the number with recurrence or death. 

Findings 

Of 23 004 studies screened, 24 trials, which comprised 5361 patients and 13 different treatments, were included in the analysis. The overall quality of evidence was rated as moderate to low. For sustained symptomatic cure, fidaxomicin (odds ratio 0·67, 95% CI 0·55–0·82) and teicoplanin (0·37, 0·14–0·94) were significantly better than vancomycin. Teicoplanin (0·27, 0·10–0·70), ridinilazole (0·41, 0·19–0·88), fidaxomicin (0·49, 0·35–0·68), surotomycin (0·66, 0·45–0·97), and vancomycin (0·73, 0·56–0·95) were better than metronidazole. Bacitracin was inferior to teicoplanin (0·22, 0·06–0·77) and fidaxomicin (0·40, 0·17–0·94), and tolevamer was inferior to all drugs except for LFF571 (0·50, 0·18–1·39) and bacitracin (0·67, 0·28–1·58). Global heterogeneity of the entire network was low (Cochran's Q=15·70; p=0·47).  

Interpretation 

Among the treatments for non-multiply recurrent infections by C difficile, the highest quality evidence indicates that fidaxomicin provides a sustained symptomatic cure most frequently. Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C difficile.

Fighting drug resistance with graphene

Via HealthNews.Africa: To tackle drug resistant bacteria, scientists turn to the world's strongest material. Excerpt:

The prevalence of antimicrobial resistant bacteria, caused by the indiscriminate application and overuse of antibiotics, has been a global issue threatening human health for several decades. Antimicrobial resistance is projected to cause the death of approximately 300 million people in the next 35 years. To prevent these deaths, researchers are seeking and putting forward alternative ways to fight bacteria.  

While efforts are geared towards introducing new drugs, a recent study published in Burns & Trauma is turning the world’s attention to a composite of the world’s strongest known material, known as graphene. 

According to the study, graphene oxide-quaternary ammonium nanocomposite is a promising antimicrobial agent for infected wound management and antibacterial wound dressing.  

Graphene shot to fame due to its extraordinary mechanical strength, optical transmittance, electrical conductivity and high specific area properties. It is the world’s strongest known material. 

The researchers posited that its excellent optical transmittance enables graphene to serve as the ideal liquid crystal display material for computer, TV and cell phone display screens. It is also known as the material with the best electrical conductivity, which can replace silicon to produce supercomputers that run faster and have lower energy consumption. 

In the biomedical fields, graphene and its deviates exhibit excellent antibacterial activity against a wide range of bacteria.

“Recent advances in nanomaterials have allowed for a considerable number of applications of graphene in antibacterial sciences. Its antibacterial properties have been attributed to the combined mechanisms of bacterial membrane perturbation caused by sharp edges and oxidative stress induction. Graphene-based composite antibacterial materials have therefore become a hot topic in scientific research,” said Tengfei Liu, co-author of the research paper. 

According to him, their study focuses on the application of graphene oxide-quaternary ammonium nanocomposite (GO-QAS) for wound repair and infection control. 

Liu noted that the GO-QAS nanocomposite exhibits excellent biocompatibility and synergistic antibacterial ability against multidrug resistant bacteria through not only mechanical membrane perturbation (including wrapping, bacterial membrane insertion, and bacterial membrane perforation), but also oxidative stress induction. 

“Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and accelerated the healing process of infected wounds by promoting re-epithelialization and granulation tissue formation. In the future, GO-QAS nanocomposite could be applied as a promising antimicrobial agent for infected wound management and antibacterial wound dressing synthesis,” Liu said.