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

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ESBL-producing E. coli

Multiple-ResistantE. coli

ESBL-producingKleb. pneumoniae

Multiple-ResistantKleb. pneumoniae

Multiple-ResistantPseud. aeruginosa

Meticillin-ResistantStaph. aureus

Vancomycin-ResistantEnterococcus faecium

Penicillin-ResistantStrep. pneumoniae

Summary of resistance trends (selected drug/bug combinations)

EARS-Net data on Antimicrobial Resistance in Ireland, Q1-2 2016

*2016 data are provisional to the end of Q2 only

Monitoring trends over time: changing epidemiology

*2015 data is projected total assuming 100% coverage (instead of 97%) by laboratories

EARS-Net data on Antimicrobial Resistance in Ireland, Q1-2 2016

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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 Asia-Pacific 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

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