What does Antimicrobial Resistance
Mean for Human Health?
Robert Cunney
Temple Street Children’s University Hospital and
HSE/RCPI HCAI/AMR Clinical Programme
Sir Patrick Dun’s Hospital
Alexander Fleming
Howard Florey and Ernst Chain
Deaths due to infection among US soldiers
in four wars
Source: US Army Medical Department, Office of Medical History
Beneficial impact of antibiotics
• Average life span USA extended by 10 years
– Curing all forms cancer: extend by 3 years*
• Control of primary infectious diseases
• Control of opportunistic infections
– Allow cytotoxic chemotherapy, radical surgery etc.
*McDermott 1982, Johns Hopkins Med J 151: 302-12
Causes of death in Ireland,
1926 - 2006
Data source: Society of Actuaries in Ireland 2011
Bacterial cervical adenitis
• Common childhood
infection
• “Antibiotics should be
targeted against S. aureus
and group A
streptococcus, and should
include a 10-day course of
oral cephalexin (Keflex),
amoxicillin/clavulanate
(Augmentin), or
clindamycin (Cleocin).”*
*Dulin M, Leach L, Am Fam Physician. 2008 Nov 1;78(9):1097-1098
Image source: Meier J, Grimmer J, Am Fam Physician. 2014 Mar 1;89(5):353-358
The first antibiotic guideline?
“Penicillin should only be used if
there is a properly diagnosed
reason and, if it needs to be
used, use the highest possible
dose for the shortest time
necessary. Otherwise antibiotic
resistance will develop”
Alexander Fleming, 1945
Scale of Antibiotic Use
• >100,000 million kg antibiotics produced since
1941
– 50% human use
• 20% hospitals
• 80% community
– 50% agricultural use
• 20% therapeutic
• 80% prophylactic/growth promotion
– 75% questionable therapeutic value
Harrison and Lederberg, Antimicrobial Resistance 1998
Summary of resistance trends
(selected drug/bug combinations)
50%
ESBL-producing E. coli
45%
Multiple-Resistant
E. coli
Proportion resistance
40%
35%
ESBL-producing
Kleb. pneumoniae
30%
Multiple-Resistant
Kleb. pneumoniae
25%
20%
Multiple-Resistant
Pseud. aeruginosa
15%
10%
Meticillin-Resistant
Staph. aureus
5%
Vancomycin-Resistant
Enterococcus faecium
0%
Year
*2016 data are provisional to the end of Q2 only
EARS-Net data on Antimicrobial Resistance in Ireland, Q1-2 2016
Penicillin-Resistant
Strep. pneumoniae
Monitoring trends over time: changing epidemiology
Number of isolates reported
3000
2500
2000
1500
1000
500
0
Year
sau
eco
*2015 data is projected total assuming 100% coverage (instead of 97%) by laboratories
EARS-Net data on Antimicrobial Resistance in Ireland, Q1-2 2016
Extended-spectrum beta-lactamase (ESBL)
• Most important resistance determinant
among Gram-negative bacteria
– Originated in non-pathogenic Kluyvera sp.
– Rapid emergence and evolution since 1990
• Global distribution via uropathogenic E. coli clones
• 40% of E. coli causing abdominal infections in AsiaPacific and Latin America*
– Geographical distribution of ESBL types
• Wider distribution of types in human vs. animal strains
*Data source: Global Study for Monitoring Antimicrobial Resistant Trends (SMART) 2003-2007,
Flow of antibiotic resistance genes in E. coli in the biosphere
Hawkey P M , Jones A M J. Antimicrob. Chemother. 2009;64:i3-i10
Global distribution of CTX-M genotypes
Hawkey P M , Jones A M J. Antimicrob. Chemother. 2009;64:i3-i10
Carbapenem-resistant Klebsiella (CRE)
in Italy
Data source: GM Rossolini, ARHAI Network Meeting, Berlin, Dec 2012
Mortality associated with CRE
bloodstream infections
AMR: comparative mortality
Development of antibiotics, and
antibiotic resistance
Human and Animal AMR Reservoirs
“One love, one heart
Let's get together and feel all right”
Bob Marley