1. Nine decades of antibiotics: how many years of antibiotic resistance?
A story with two endings…
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
Slides:

2. ReAct.

4. 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

6. ReAct.

7. AMR bacteria

8. MRSA

9. Key milestones in MRSA epidemiology

10. MRSA bacteraemia, England 2001-20134 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

11. Local reductions: MRSA

12. 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.

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

14. MRSA bacteraemia, England 2001-20134 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

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

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

17. CPE

18. National trends: mandatory surveillance in England

19. 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

20. 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:
Peleg & Hooper. N Engl J Med 2010;362:

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

22. CPE
Rapid spread
AMR
Clinical impact

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

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

25. 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.

26. 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:

27. Emergence of CRE in the UK
ESPAUR 2017.

28. The tip of the iceberg…
0.5%1 x 186,393 = 932 (!) 0.1%2 x 186,393 = % x m* = 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:

29. CRE in the USA
NHSN / NNIS data; MMWR 2013;62:

30. 10 decades of antibiotics (the happy ending)
06 April 2028
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
Slides:

31. 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: , and Review on AMR.

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

33. 10 decades of antibiotics (the other ending)
06 April 2028
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
Slides:

34. 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: , and Review on AMR.

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

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

37. Nine decades of antibiotics: how many years of antibiotic resistance?
A story with two endings…
Jon Otter, PhD FRCPath
Imperial College London
@jonotter
Blog:
Slides: