Antimicrobial resistance and the need for stewardship Dr Nick Brown RCP Acute Medicine conference, 16 April 2018
Fleming s laboratory, St Mary s Hospital, London (Photo N M Brown )
It is not difficult to make microbes resistant to penicillin in the Laboratory and the same thing has occasionally happened in the body. 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 under dose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant. Alexander Fleming Nobel Lecture, 11 December 1945
Darwinian survival of the fittest Antibiotics kill susceptible bacteria; resistant ones survive Level of antibiotic use affects the prevalence of resistance Resistant organism in susceptible population Susceptible cells killed by antibiotic Resistant progeny grow Slide: US Centers for Disease Control & Prevention (CDC)
The more you use antibiotics, the less effective they become!
70 Years of Antibiotics and Resistance Development of new antibiotic Emergence of resistance 6 Lets Talk Antibiotic Resistance
House of Lords Committee on Science and Technology - Seventh Report This enquiry has been an alarming experience, which leaves us convinced that resistance to antibiotics and other anti-infective agents constitutes a major threat to public health, and ought to be recognised as such more widely than it is at present. Lord Soulsby of Swaffham Prior Chairman 17 March 1998 http://www.parliament.the-stationery-office.co.uk
Proportion of carbapenem resistant Klebsiella pneumoniae in participating countries 2009 EARS-NET data available online
Proportion of carbapenem resistant Klebsiella pneumoniae in participating countries 2010 EARS-NET data available online
Proportion of carbapenem resistant Klebsiella pneumoniae in participating countries 2011 EARS-NET data available online
Proportion of carbapenem resistant Klebsiella pneumoniae in participating countries 2014 EARS-NET data available online
The resistance ratchet keeps turning Pathogen Established problems Emerging threats E. faecium VRE, HLGR, Amp-R Linezolid-R, Dapto-R, Tige-R S. aureus MRSA Vanco-R, Linezolid-R, Dapto-R Klebsiella ESBLs Carbapenemases, Colistin-R Acinetobacter MDR, Carbapenemases Tige-R, Colistin-R Pseudomonas MDR, except Colistin Carbapenemases, Colistin-R Enterobacter AmpC, ESBLs Carbapenemases E. coli Cipro-R, ESBLs Carbapenemases 5 of 7 ESKAPEEs are Gram-negative Increasing reliance on carbapenems Rising incidence of carbapenem resistance The resistance issue for the next 5-10 years Slide: Neil Woodford, AMRHAI VRE=vancomycin resistant enterococci; HLGR=high level gentamicin resistant; Amp=ampicillin; MRSA=methicllin resistant Staphylococcus aureus; ESBL=extended spectrum beta-lactamase; MDR=multidrug resistant; cipro=ciprofloxacin; Dapto=daptomycin; Tige=tigecycline
Antibiotic use benefits the individual and Society HIV/AIDs related infection Neonatal infection Diarrhoea Pneumonia Tuberculosis STDs: Chlamydia Gonorrhoea Surgery: essential, elective, cosmetic Puerperal fever Trauma: war, accidents Cancers Cardiovascular Transplants Joint replacements: hips, knees prostheses Pneumonia Otitis media Tonsillitis Inherited disorders: CF COPD Bronchitis 0 10 20 30 40 50 60+ Age (years) Adapted from White, A : Boston, 2006
If we don't take action, then we may all be back in an almost 19th century environment (CMO Dame Sally Davies 11 Mar 2013) A post-antibiotic era means, in effect, an end to modern medicine as we know it (WHO DG Margaret Chan - 14 Mar 2012)
Impact of antimicrobial resistance on world GDP (trillions US$) Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. The Review on Antimicrobial Resistance Chaired by Jim O Neill December 2014
Antimicrobial resistance already contributes to 25,000 deaths per year in the EU The loss to EU healthcare and productivity is estimated to be 1.5bn per year The are only around 40 candidate antibiotics in clinical development. Only 6 are expected to be licenced before 2024 In contrast, over 170 diabetes drugs and 700 cancer drugs are in various stages of development https://www.newstatesman.com/sites/default/files/ns_msd_supplement_nov_2017.pdf
Infection prevention and control Prevent no infection, no need for antibiotics Stewardship Protect use antibiotics appropriately Stimulate new drugs Promote develop new treatments and diagnostics Research Address knowledge gaps Awareness Public understanding International collaboration A global problem Surveillance Know and react http://www.gov.uk
Antibiotic use in Europe Goossens et al Lancet 2005
Correlation between penicillin use and prevalence of resistance in Streptococcus pneumoniae Goossens et al Lancet 2005
Goals of Antimicrobial Stewardship Improve patient outcome Improve patient safety minimize unintended consequences of antimicrobials Reduce resistance Reduce healthcare costs without adversely impacting quality of care
80% of antibiotics are prescribed in general practice Simpson et al. J. Antimicrob. Chemother. 2007;59:292-6; ESPAUR Annual Report 2015
http://fingertips.phe.org.uk/profile/amr-local-indicators/data#page/0
http://fingertips.phe.org.uk/profile/amr-local-indicators/data#page/0
Trends in prescribing of antibacterials in General Practice in England Changes 2007-2012 Primary Care dispensing data: Health and Social Care Information Centre and NHSBSA
As ciprofloxacin & cephalosporin use has decreased so has resistance Antibiotic resistance data from E.coli in blood cultures 2004 2013 % blood culture isolates resistant Ciprofloxacin Cephalosporin Livermore et al. Lancet Infectious Diseases 2013
Percentage Review of antibiotics at 48-72h 30 25 20 15 10 5 Percentage of antibiotic prescriptions reviewed within 72 hours with a stop decision documented Percentage of antibiotic prescriptions continued without a review date or duration Percentage of antibiotic prescriptions continued with a review date or duration Percentage of antibiotic prescriptions switched from the IV to oral route during the 72 hour review 0 2017/18 Q1 2017/18 Q2 2017/18 Q3 Source: ESPAUR Report 2017, CQUIN data and PHE AMR fingertips
Limitations of current antibiotic prescribing Remains empirical Diagnostic uncertainty compounded by antibiotic resistance Potential consequences: Wrong organism targeted Wrong antimicrobial agent selected Unnecessary exposure to side effects Expenditure without benefit Adapted from Finch, EU Interdepartmental conference 2005
To Dip or Not To Dip a patient centred approach to improve the UTI management in the care homes Results Jul-Dec 2015 NHS Bath and North East Somerset CCG 56% reduction in the proportion of residents who had an antibiotic for a UTI 67% reduction in the number of antibiotic prescriptions 82% reduction in the number of residents prescribed antibiotic prophylaxis Unplanned hospital admissions for UTI, urosepsis and AKI reduced in nursing home population following implementation Beech E. Oral presentation at Federation of Infection Societies (FIS) conference November 2017
Over the counter purchase of antibiotics without prescription No. pharmacies visited Athens, Greece No. dispensing ciprofloxacin 102 54 Information from Matthew Dryden, Peter Hawkey and John Wain 30
1 March 2015 Last updated at 02:30