ASA 2017 Adelaide.
This year the concept of One Health was a major focus. Professor Stefan Schwarz, Institute of Microbiology and Epizootics, Berlin, presented one of the plenary sessions titled "One Health Aspects of Antimicrobial Resistance in Gram Negative Bacteria and Enterococci." Professor Schwarz explained the One Health Triad, which consists of People, Environment and Animals; recognising that human health is interconnected to the health of animals and the environment. Interdisciplinary collaborations and communications are necessary to solve health care, especially the most critical area of continuing antimicrobial resistance. The main drivers are the integration between humans and animals (companion, farm and wild); increasing population size, increasing meat consumption, leading to a greater use of resources and corresponding waterway pollution; expanding human population into new habitats, where people are potentially exposed to new viruses and organisms as the human population encroaches on wildlife areas; climate changes bringing tropical diseases to new geographical areas--it is estimated that up to 75% of emerging or re-emerging diseases are either zoonotic or vector-borne e.g. Dengue virus, West Nile virus, Chikungunya virus, Zika virus. Furthermore global trade and travel can potentially turn local outbreaks into pandemics. For further reading on One Health, visit www.onehealthinitiative.com.
Carbapenemase-producing organisms (CPO) are still top 'bad boys' of the WHO-listed antimicrobial resistant threats. The mortality rate from serious infections caused by CPO is the same as for Ebola! It is predicted that by 2050, at least 10 million people will die annually from antibiotic resistant infections. Professor Timothy Walsh (Cardiff University, Wales) gave an excellent Howard Florey oration, "UN Agenda on Antimicrobial Resistance: Dream or Scream?" In 2009, Prof Walsh and his team where the first to discover the New Delhi Metallo-[beta]-Lactamase (NDM) in India, and he is a leading researcher in this field. He discussed his involvement with the BARNARDS project, funded by the Gates foundation, which aims to investigate the problem of antibiotic resistant infections, and to determine possible solutions, in neonates in low income countries such as Nigeria, Pakistan, Bangladesh and Ethiopia.
Tim spoke about the difficulties in setting up a laboratory in places that often don't have adequate sanitation systems, trying to get supplies through corrupt officials and working in countries with civil unrest. Other confounding problems include the easy availability of antibiotics across-the-counter, huge amounts of antibiotics included in farm animal supplements, especially in poultry and pig farming, and a lack of infection control programmes. Antibiotic resistant organisms, including MRSA, ESBLs and CPO have been found in a variety of companion and farm animals around the world. In some countries contaminated animal manure is then sprayed onto crops!
The emerging issue of colistin resistance, due to the mobile plasmid-mediated lipid-A transferase gene mcr-1, was discussed by a number of presenters. Professor Stefan Schwarz explained that colistin has been around since the 1950s, but went out of favour in 1980s due to nephrotoxicity and neurotoxicity. Colistin is currently used for cystic fibrosis patients and gut decontamination but there has been a recent resurgence of use as part of treatment regimens for infections caused by carbapenem resistant organisms. It is used in huge quantities in poultry and pig farming. Chromosomal resistance to colistin has been known for years and some Enterobacteriaceae are intrinsically resistant e.g. Proteus, Serratia. This type of resistance is not a big threat as spread would have to be via a clonal outbreak. However of more concern is the mcr-1 gene, which was found in E.coli in 2015 (incidentally by Professor Timothy Walsh!). This mobile resistant element is mostly carried on a self-conjugating plasmid without other resistance markers (it can form its own circular mobile element and move between plasmid and chromosome), but has also been found in larger plasmids, carrying a variety of resistance markers. Of course these attributes make for excellent opportunities for co-selection and persistence! mcr-1 has been found globally and more commonly in animal strains (with such large colistin consumption, it's no wonder).
Dr Andrew Ginn, Westmead Hospital, Sydney, discussed the results of their study, looking at the colistin MIC of 4555 Enterobacteriaceae (excluding those intrinsically resistant species), from 2007 to 2016. They found 96 (2.1%) strains resistant to colistin. PCR and sequencing confirmed that two E.coli isolates harboured mcr-1. Both strains were found in patients with UTI, but were isolated two years apart, with no geographical connection, and neither patient had recent travel history. The strains were distinct sequence types and plasmids, but the plasmids were identical to those that have been found in Asia. It is possible that the strains were transmitted by migratory birds.
Another area covered by several presenters was the human microbiota or microbiome (microbiota usually refers to the community of organisms/viruses/parasites present, whereas the microbiome refers to the collective microbial genetic pool). Microbiome studies have grown exponentially in the last few years as next generation sequencing systems have become faster and cheaper. The Human Microbiome Project, which was completed in 2003, cost nearly 3 billion dollars; compared to current costs of <$1000. Microbiome research is helping to better understand the development and spread of resistance, especially the interplay between the environment, humans and agriculture (back to the One Health theme again). The first Plenary Session was presented by Dr Geraint Rogers, Flinders University, Adelaide, a molecular microbiologist and microbial ecologist. His talk was titled "Antimicrobial Resistance and the Human Microbiome". Dr Rogers discussed how new studies have shown that early antibiotic use in children can have lifelong consequences for immune response (e.g. weakened response to vaccines), development of diabetes, obesity risk, and future mental health issues (reference= Nat Immunol. 2014 Apr;15(4):307-10. doi: 10.1038/ni.2847). In adults, antibiotic use can also affect lipid and glucose metabolism, immune regulation, CNS function, nutrition, and prevention of infection. Antibiotic pressure leads to selection, mutation and adaptation of the microbiota. This is often systemic. The antibiotics with the greatest 'antibiotic risk index' includes cephalosporins, carbapenems, quinolones and clindamycin. The Royal Adelaide Hospital has a research programme, developing faecal microbiota transplants for people who have had many courses of antibiotics as well as recurrent Clostridium difficile infections.
Professor Anton Peleg, Director of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, continued the microbiome topic with a symposium session titled "The gut as a resistance reservoir". Anton described how humans are composed of 10x as many bacterial cells as human cells; with the highest density in the gut. These gut bacteria play a critical role in human health, including nutrition, immunity, and protection against pathogenic organisms. Associations or commonalities between gut health and human health have been found with a variety of diseases including inflammatory bowel disease, type 2 diabetes, obesity, colorectal cancer, liver cirrhosis and rheumatoid arthritis. The gut is under constant flux from the environment and other selective pressures, creating a huge 'resistome pool'. Anton also reiterated that the impact of antibiotics early on in life appears to lead to less bacterial diversity and less stability of flora. At the time of antibiotic use e.g for [beta]-lactams, there is a big increase in the number of organisms in the gut expressing plasmid mediated resistance, and these can remain in the gut for months afterwards. Metagenomics are now being used to characterise the antimicrobial resistance reservoir of the gut--PCR can be used to target specific genes, or functional metagenomics can be used to find specific plasmids and express in a host strain, or next generation sequencing can be used to align to known resistance genes.
Moving away from the gut, but still with the microbiome topic, Dr Alkis Psaltis, Department of Otolaryngology, Queen Elizabeth Hospital, Adelaide, spoke about the microbiome of the upper airways. Chronic rhino sinusitis affects 10-20% of the population, across all age groups, with symptoms including pain, discharge, poor smell, and nasal blockage. It is a debilitating condition that results in poor life functionality for many people. The cause is largely unknown but could be due to bacteria (with biofilm formation in the nasal/sinus epithelium), fungal, allergic reactions or polyps. A dysbiosis of the normal sinus flora can lead to chronic rhino sinusitis. Dr Psaltis is investigating ways to reverse this dysbiosis including snot transplants!
There were many more interesting and informative presentations during this three day meeting. If you are interested in all things antimicrobial, the next ASA meeting will be held in Sydney, February 2018 (www.asainc.net.au). I totally recommend attending!
Canterbury Health Laboratories, Christchurch
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|Title Annotation:||Australian Society of Antimicrobials|
|Publication:||New Zealand Journal of Medical Laboratory Science|
|Date:||Aug 1, 2017|
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