Antimicrobial Resistance – Links to papers /resources

*** For any stewardship/education sessions – this post will serve as a resource for links to the evidence quoted- I’ll try and keep it up-to-date as I can***

“Hi, I’d really like an overview on where we are with antibiotic resistance!”  – recommend the CDC overview- colorful, diagramatic, comprehensive

“Hi, tell me about Carbapenem-Resistant Enterobacteriaceae (CRE)  and why everyone thinks this is seriously bad stuff” – great review in the Mayo Clinic Proceedings – Vasoo et al 2015

****Selection and transmission of resistance*****

Sub-lethal doses of antibiotic can select for resistance (eg wastewater…)  Gulberg  2011
Sublethal doses of biocide can select for resistance Forbes 2014
Resistance spread by the bacteriophage network – Modi 2013
Rapid spread of carbapenem resistance between multiple species (Klebsiella, Enterobacter, Serratia, E.coli… )  caused by jump of plasmid to multiple species – Mathers 2011, Conlan 2012 and  then jumping to high-fitness strains, evolving and spreading further.
Nepal MDR Klebsiella outbreak featuring horizontal gene transfer –Chung 2015
Antibiotic levels in wastewater above serum therapeutic levels –Larsson 2007
The widely-quoted correlation between antibiotic use on a population level and antibiotic resistance –Albrich 2004
Antibiotic resistance genes in cave microbiome Bhullar 2012
Is there a link between resistance in food-animals and resistance in humans? Examples:
Lazarus2015 Systematic review– plenty of studies saying probably, yes
More under the cut….

Plasmid-mediated transmission a likely mechanism – Wang 2015

A summary of the “evidence for” –  the link between animal antibiotic use and human ESBL infection – report written by the Soil Association here.

As I feel I should offer a balance of views I’ll also give you an “evidence against” report by the National Office of Animal Health here, (who gave evidence to the House of Lords Select Committee). I personally don’t agree with many of the statements (resistance increasing is old, new antibiotics coming,  selective picking of evidence, lack of evidence using incomplete methods =/= lack of occurrence), but will leave you to consider your own views.

The CDC position is that there is a significant link.

****Antibiotic-gut-resistance axis *****

Giving antibiotics orally had significant effects on the gut microbiota and resistance carriage in mouse model, Giving IV- very little effect. Zhang 2013
The long term effects of antibiotics on diversity of the microbiome –Dethlefsen 2010
Intestinal dominance associated with bloodstream infection in haematology patients –Taur 2012
Gut colonisation with ESBLs in high-risk patients – Biehl 2014
The human gut resistome – Shaik 2015
Commensal enterococci can actively kill multidrug-resistant enterococci – Gilmore 2015

Gut-carriage of resistance genes reflect country-specific antibiotic use in human and animals Forslund 2013

***Do we really know what we’re doing ? Antibiotics may increase risk of infection by depleting the host ‘protective’ microbiome*****

Antibiotic depletion of mouse host microbiome may reduce Influenza A immune response – Ichinohe PNAS 2011
Antibiotics – stop killing the beneficial bacteria – Commentary- Blaser, Nature2011
Antibiotic treatment of diarrhoea in children reduces time until recurrence – Rogawski 2015

Antibiotic treatment of asymptomatic bacteruria can increase risk of subsequent UTI – Cai 2012

Antibiotic use increases risk of Crohn’s disease – Shaw 2011 and discussed here

Major position papers/overviews, more molecular biology, changing prescribing – continued….

UK Chief Medical Officer Report 2011 Vol 2: Antimicrobial Resistance

Review on Antimicrobial Resistance 2014 – Report commissioned by UK Government

World Health Organisation – Resistance factsheet 

The CDC overview – very nice, shiny infographics.

Use of antibiotics in agriculture –Soil Association report 

Others want to do their bit – Antibiotic Resistance Coalition (including farming, consumer, developing world groups)  Declaration on Antibiotics 2014

Some good writing:

Antibiotic Resistance is a Social Problem – Smith 2015

Viewpoint:  “We lived with arrogant optimism that we had conquered infections[…] How wrong we were! Bacteria have finally reclaimed their premier status and superiority and won the war against humans. They are literally mocking our intellect, knowledge and antibiotic weaponry”-  Abdul Ghafur, Consultant in Infectious Diseases and Clinical Mycology, Apollo Hospital, Chennai.Viewpoint   Article here.

Resistance Data:

EARSS – European Resistance Data, interactive maps 

Into the molecular biology of resistance:
A paper which, though very dense and wordy makes an excellent point comprehensively – we need to stop thinking about the spread of resistance being about bacterial species, and start looking at the unit of transmission – be it strain, plasmid, transposon..Antibiotic resistance shaping the population biology of bacteria.Baquero 2013

An extensive paper covering environmental pollution: Martinez- Environmental pollution by antibiotics and by antibiotic-resistance determinants 

Faecal Transplantation

Case report of obesity associated with faecal transplantation Alang 2015 (think- take with a pinch of salt… but interesting given well-reported correlations between microbiota and obesity – see Turnbaugh 2009)

Mice given faecal transplants take on the behaviour of  their donor – Collins 2013

Refractory C diff in pt with VRE resolved with faecal transplant – Jang 2015

Faecal transplants -first reported use in 4th Century in China for gastrointestinal infection -Zhang 2012

Changing Prescribing:

UK Department of Health guidance on changing prescribing 

Charani E et al. Understanding the Determinants of Antimicrobial Prescribing Within Hospitals: The Role of “Prescribing Etiquette” Clin Infect Dis 2013 –
Harbarth et al – sociocultural determinants of prescribing (France vs Germany)

National MRSA rates run along with fair play of national football teams: a cross-national data analysis of the European Football Championship, 2008. (great use of pseudostats)

Michie S, van Stralen M, West R The behavior change wheel: A new method for characterising and designing behaviour change interventions. Implementation Science 2011 – study of a public health intervention aimed at increasing vaccination rates – Nyhan et al – more information does not necessarily change behaviour! – Climate change : not a matter of education
Example of behaviour change interventions with clear messages:
Bao et al PLOSone 2015  – Massive reduction in antibiotic use in China 2010-14 (Intervention: noncompliance = disciplinary proceedings including loss of career).
Microbiome and effects on behaviour  (mice take on the behaviour of their microbiome donors)  – Collins et al 2013

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