Nine decades of antibiotics: how many years of antibiotic resistance? A story with two endings… Jon Otter, PhD FRCPath Imperial College London j.otter@imperial.ac.uk @jonotter Blog: www.ReflectionsIPC.com Slides: www.jonotter.net

ReAct.

But I would like to sound one note of warning…There may be a danger, though, in underdosage. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant. Here is a hypothetical illustration. Mr X has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs X dies. Who is primarily responsible for Mrs X’s death? Why Mr X whose negligent use of penicillin changed the nature of the microbe. Moral: If you use penicillin, use enough. Alexander Fleming, Nobel Lecture, December 11 1945.

ReAct.

AMR bacteria

MRSA

Key milestones in MRSA epidemiology

MRSA bacteraemia, England 2001-2013 4 5 6 Mandatory reporting, 2001 ‘Gettting ahead of the curve’, 2002 ‘Winning ways’, 2003 ‘Towards cleaner hospitals’, 2004 ‘Cleanyourhands’, 2004 Targets introduced, 2004 Cleanliness improvement, 2005 ‘Going further faster’, 2006 Root cause analysis, 2006 Revised national guidelines, 2006 Deep clean, 2007 Screening elective admissions, 2008 Universal screening, 2010 8 9 10 3 7 1 2 11 12 13

Local reductions: MRSA

Does hand hygiene explain the “MRSA miracle”? ‘The Cleanyourhands campaign was associated with sustained increases in hospital procurement of alcohol rub and soap, which the results suggest has an important role in reducing rates of some healthcare associated infections.’ Stone et al. BMJ 2012;344:e3005.

Why no reduction in MSSA bacteraemia…? Stone et al. BMJ 2012;344:e3005.

MRSA bacteraemia, England 2001-2013 4 5 6 Mandatory reporting, 2001 ‘Gettting ahead of the curve’, 2002 ‘Winning ways’, 2003 ‘Towards cleaner hospitals’, 2004 ‘Cleanyourhands’, 2004 Targets introduced, 2004 Cleanliness improvement, 2005 ‘Going further faster’, 2006 Root cause analysis, 2006 Revised national guidelines, 2006 Deep clean, 2007 Screening elective admissions, 2008 Universal screening, 2010 8 9 10 3 7 1 2 11 12 13

% invasive S. aureus isolates resistant to meticillin. MRSA in Europe, 2016 % invasive S. aureus isolates resistant to meticillin. EARS-Net 2018.

% invasive S. aureus isolates resistant to meticillin. MRSA in Europe, 2000 to 2016 % invasive S. aureus isolates resistant to meticillin. EARS-Net 2018.

CPE

National trends: mandatory surveillance in England

The emerging threat of CPE Pathogen CPE MRSA VRE C. difficile Resistance +++ + +/- Resistance genes Multiple Single n/a Species HA vs CA HA & CA HA At-risk pts All Unwell Old Virulence ++ Environment

Rising threat from MDR-GNR % of all HAI caused by GNRs. % of ICU HAI caused by GNRs. Non-fermenters Acinetobacter baumannii Pseudomonas aeruginosa Stenotrophomonas maltophilia Enterobacteriaceae Klebsiella pneumoniae Escherichia coli Enterobacter cloacae CPO CPE Hidron et al. Infect Control Hosp Epidemiol 2008;29:966-1011. Peleg & Hooper. N Engl J Med 2010;362:1804-1813.

Extended-spectrum beta-lactams Creating a monster Enterobacteriaceae ESBLs CPE Extended-spectrum beta-lactams Carbapenems

CPE Rapid spread £ AMR Clinical impact

% invasive K. pneumoniae isolates resistant to carbapenems CRE in Europe, 2016 % invasive K. pneumoniae isolates resistant to carbapenems EARS-Net 2018.

Emergence of CRE in Europe, 2005-2016 EARS-Net 2018.

What drives the European ‘north-south divide’? Antibiotic use Infection control staffing Single room availability National debt 1. ECDC Point Prevalence Survey, 2013. 2, National debt as a percentage of GDP. "Eurostat public debt GDP" by Eurostat. Licensed under Attribution via Wikimedia Commons.

What drives the European ‘north-south divide’? Correlation between MRSA rate in BSIs and an indicator for fair play from the European Football Championships (red or yellow cards / 100 min)1 Correlation between national chocolate consumption and rate of Nobel prize winners.2 Meyer et al. Infection 2012 in press. Messerli FH. New Engl J Med 2012;367:1562-4.

Emergence of CRE in the UK ESPAUR 2017.

The tip of the iceberg… 0.5%1 x 186,393 = 932 (!) 0.1%2 x 186,393 = 186 0.1% x 15.892m* = 15,892 * Admissions to NHS acute hospitals, Financial Year 14/15. NHS Confederation, Key Statistics on the NHS, Taking our carriage rate of CRE – 0.5% and applying it to our yearly patient admissions, means we can see close to 900 CRE positive patients 0.1% which is a conservative estimate, apply that, and its 186 0.1 is the conservative estimate, applying that to all NHS hospitals, 16,000 pos patients, currently reporting around1600, 10 fold underestimate of CRE positive patients Mookerjee et al. ECCMID 2016. Otter et al. J Antimicrob Chemother 2016;71:3556-356.

CRE in the USA NHSN / NNIS data; MMWR 2013;62:165-170.

10 decades of antibiotics (the happy ending) 06 April 2028 Jon Otter, PhD FRCPath Imperial College London j.otter@imperial.ac.uk @jonotter Blog: www.ReflectionsIPC.com Slides: www.jonotter.net

Prevention is better than cure Reduced antibiotic use Improved diagnostics Surveillance for action Phages and vaccines Highlight high cost of AMR New antibiotics Public awareness Pay and recognition for AMR folk Based on Laxminarayan et al. Lancet Infect Dis 2013;13:1057-1098, and Review on AMR.

Emergence of CRE in Europe, 2005-2028 EARS-Net 2028.

10 decades of antibiotics (the other ending) 06 April 2028 Jon Otter, PhD FRCPath Imperial College London j.otter@imperial.ac.uk @jonotter Blog: www.ReflectionsIPC.com Slides: www.jonotter.net

Prevention is better than cure Reduced antibiotic use Improved diagnostics Surveillance for action Phages and vaccines Highlight high cost of AMR New antibiotics Public awareness Pay and recognition for AMR folk Based on Laxminarayan et al. Lancet Infect Dis 2013;13:1057-1098, and Review on AMR.

Emergence of CRE in Europe, 2005-2028 EARS-Net 2028.

How do you feel about the next decade of AMR? Based on a survey of 52 respondents on Twitter and 82 on www.reflectionsipc.com

Nine decades of antibiotics: how many years of antibiotic resistance? A story with two endings… Jon Otter, PhD FRCPath Imperial College London j.otter@imperial.ac.uk @jonotter Blog: www.ReflectionsIPC.com Slides: www.jonotter.net