Are we facing a superbug apocalypse? 21ST CENTURY MEDICINE LECTURE SERIES: TODAY S RESEARCH, TOMORROW S HEALTHCARE Tackling infections, locally and globally www.sydney.edu.au/mbi Are we facing a superbug apocalypse? - the Antibiotic Paradox Don't it always seem to go That you don't know what you've got till it's gone Joni Mitchell (1970), Big Yellow Taxi From IDSA Capitol Hill talk by Brad Spellberg May 11 2010. www.idsociety.org/content.aspx?id=4810 fast forward to 2013 A post-antibiotic era means, in effect, an end to modern medicine as we know it Sep 28, 2013 US: 4.6% of global population, 46% of global ab market CDC: resistant organisms infections in >2 million, 23,000 deaths in US each year.. Some interventions, like hip replacements, organ transplants, cancer chemotherapy and care of preterm infants, would become far more difficult or even too dangerous to undertake Dr. Margaret Chan, director general WHO. March 16, 2012
Figure 1 Total outpatient antibiotic use in 26 European countries in 2002 AUS 132 days in hospital, 82 in ICU 12 operative procedures Blood stream infections: Enterobacter cloacae x 1 Enterobacter cloacae (ESBL) x 1 MRSA x 2 Pseudomonas aeruginosa x 2 A.baumannii (MRAB) x 2 Klebsiella pneumoniae (ESBL) x 1 Enterococcus faecalis x 1 Providencia sp x 1 Candida parapsilosis (yeast) x 1 Outcome measure 1: ICU: Patient survival = success ++ Outcome measure 2: ID/Micro: 130d: ICU, Burns. MRO exposure ++ Antibiotic use ++ = infection control disaster The Lancet Volume 365, Issue 9459 2005 579-587 the etiquette of antibiotic prescribing individual patient care approach just in case it is infection (defensive prescribing) risk of individual failure >> long-term loss of efficacy more antibiotics, longer duration, broader is safer vs. societal approach attempts to conserve antibiotics, stewardship avoid collateral selection (resistant organisms, C.difficile, ) against law of entropy? >50% antibiotic use in hospitals repeatedly shown to be inappropriate antibiotic resistance is Darwinian, BUT few new drugs in the development pipeline eg. 15/18 major pharma suppliers have left antibiotic field * Bartlett JG, Clin Infect Dis, 2013 http://www3.weforum.org/docs/wef_globalrisks_report_2013.pdf
one slide crash course about Superbugs??!! some bacteria are antibiotic susceptible but virulent, some are resistant but cause infection only in a small minority bacteria are part of our commensal flora. Staph on skin, E.coli as part of gut flora Gram (E.coli) also in other niches: animals, food, environment bacteria transfer genetic material very efficiently codes for resistant enzymes protect bacteria from antibiotics the more antibiotics inhibited, the more multiresistant some confer extreme resistance & risk of untreatable infection: ESBLs; CREs (NDM, KPC) THE BLACK PLAGUE Spread by merchants and travelers, the plague killed > 1/3 of Europe s population within 5 years eg. Staph eg. E.coli, Klebsiella https://qed.princeton.edu/index.php/user:peak/transclude CREs 2007 NYC 21% Klebsiella KPC+ NDM-1+ 2008 NDM-1: 2009-2011 Red Plague? KPC+ 1996 KPC+ 2003
Klebsiella pneumoniae in blood cultures resistant to 3rd Gen Cephalosporins (cefotaxime/ceftriaxone) Trends in MRSA and ESBL E.Coli bacteremia in Europe. Extrapolated EARSS nos for 2003 2009, and trajectories based on regression analysis for 2010 2015. 2011 2005 2.5 x 30 day & 2.9 x hospital mortality ESBL+ E.coli MRSA Data from EARSS, http://www.ecdc.europa.eu/activities/surveillance/ears-net/ de Kraker MEA, Davey PG, Grundmann H, PLoS Med 8(10) 2011. Resistant infections associated with higher rates of death, illness and prolonged hospital stay India makes ~ 1/3 world s antibiotics ($12.4 billion) 5,000+ manufacturers of generic antibiotics 23% of city dwellers have no toilets 2012 WHO report In 2007 ~45,000 cipro doses released daily downstream of Hyderabad sewage plant Jason Gale, Bloomberg Press, May 8, 2012 >100 million NDM-1 +ve in India Walsh et al, Lancet ID, 2011 Pakistan hospitals: 37% CRE+ Nahid F. J Inf Public Health 2013 171 environment swabs - 51/171 (29.8%) NDM-1+ 50 water samples - 2/50 (4%) NDM-1+ India has lost the war against the toughest forms of antibiotic resistance, largely because of poor sanitation, unregulated use of antibiotics and an absence of drug resistance monitoring
Ecology of food-borne organisms c/o Seamus Fanning, UCD Institute of Food and Health, Dublin Environment Rivers Land mass Streams Animal feeds offal drinking water Animals Cattle Poultry manure spreading Sheep Pigs farm effluents abattoirs processors meat handling processing consumption sea sewage Humans Urban swimming Rural Hospitalised contact Civilization is the distance man has placed between himself and his (or his animals ) excreta ~ Brian Aldiss, adapted mostly for growth promotion, despite no data for efficacy As we start to understand the gut microbiome, are we creating genetically modified animals? Source: PEW Charitable Trust ESBL rates in various types of meat - Netherlands 2011 Overdevest I. Emerg Infect Dis 2011 Solutions Smart companies and smart governments: leadership / governance / political will incentives to pharma diagnostics, rewarding innovation Behavioural: promote the special / fragile nature of antibiotics identify personal and societal triggers to behaviour change Structural: hospitals (eg. infection control), sanitation Organisational: engagement with all identified specialities, interest groups International: resistance does not respect borders Legislative: worldwide ban on non-therapeutic use in animals Sustained: the world has a short attention span
University of Sydney, Feb 7-8, 2011 Competition for government commitment Antibiotic resistance an intangible problem c/w obesity, cardiac disease, mental illness like climate change? seen as someone else s problem to tackle, even within medical specialities role of outside factors - can local investment turn things around without international commitment AMRSC, MBI Medical J Austr 2011. 194:281-3 Human infections one health research domains and themes multidisciplinary infection management and control Zoonotic infections Animal infections Field to laboratory to bedside Infection control and biosecurity Surveillance and response Policy and communication Education and outreach Environment and sustainability Plant and soil health exploring the role that universities can play in linking science to social and political action, stimulating innovation and access, and supporting research to shape the response to the challenges of antimicrobial resistance Behavioural aspects and drivers of antibiotic use Stewardship interventions hospital, community, veterinary Antibiotic use guidelines at local and national level Infection control initiatives Resistance surveillance Diagnostics: molecular detection of infection, resistance targets; New antimicrobial compounds Genetics of antibiotic resistance Biomarkers to differentiate viral from bacterial infection One health partnerships: veterinary and medicine International partnerships: education, capacity building The Broad Street Pump {in problems of antibiotic use}.. as in state affairs, by foreseeing them at a great distance, the evils which might arise from them are soon cured; - but when from want of foresight, they are suffered to increase to such a height that they are perceptible to everyone, there is no longer any remedy Niccolo Machiavelli in The Prince (1513)