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Ensuring Effective Antibiotics in the 21st Century


Leading causes of mortality in low-income countries, 2004


Leading infectious causes of death in low-income countries 2005 (estimates) 3.5 < 5 years old

Deaths (millions)

3.0

> 5 years old

2.5 2.0 1.5 1.0 0.5 0

ARI

Diarrhoea AIDS

TB

Malaria Measles


Antimicrobial resistance: bacterial, viral, and parasitic infections, 2009 HIV/AIDS

Tuberculosis

Malaria

Source: WHO


Proportion of tuberculosis cases with first-line drug resistance, UK, 2000-2008

Source: HPA, UK


Percent MDR TB among new cases 1994-2007

Source: WHO, 4th global TB report


Rates of resistance in hospital intensive care units worldwide 80 70

Infection Rate (%)

60 50 40

Asia (707 ICUs) Africa (89 ICUs)

30

Rest of World (6291 ICUs)

20 10 0 ESBL-producing

MRSA

VRE Type of Bacteria

Source: Vincent JL et al JAMA302(21):2323-2329.

All Gram Positive

All Gram Negative


MRSA and VSRE as percentage of all bacteria isolated from intensive care units, 2007 Proportion of MRSA and VRE isolates of all micro-organisms isolated from ICUs in different regions of the world (2007) 25

Proportion of isolates (%)

20

15

MRSA VRE 10

5

0

*

Africa

N. America

Central/South America

E. Europe

Source: Vincent, J.-L., et al. JAMA 302(21): 2323-2329

Asia

Oceania

W. Europe

ALL


Positive blood culture and deaths, neonates with suspected sepsis, Mwanza- Tanzania 60 9 36 50

Death (%)

40

30

91 149 Positive

55 58

20

10

23

151

0 Culture

Gram Reaction Parameter

Source: Kayange M, et al. Pediatrics 10: 39.

ESBL

MRSA

Negative


Use of second and third generation antimicrobials and cost, 2004 estimates Cost ratio of alternative drugs to first-line antimicrobials for common acute infections

Source: WHO /MHS 2004 International Drug Price Indicator Guide


"Misuse of drugs could result in selection of resistance" Alexander Fleming, 1945


Interval between start of antibiotic use and first report of resistance Intervals between start of antibiotic clinical use and the 1st report of resistance Linezolin Carbapenems 3rd Gen Cephalosporins 2nd Gen Cephalosporins Gentamicin Cephalothin Methicillin Vancomycin Tetracycline Erythromycin Chloramphenicol Streptomycin Penicillin Sulfonamides 1935

1945

1955

1965

1975

1985

1995

2005

Source: Jacoby, G. A. (2009). History of Drug-Resistant Microbe. Antimicrobial Drug Resistance. D. L. Mayers, Humana Press: 3-7. Bergstrom CT, Feldgarden M (2008). The ecology and evolution of antibiotic-resistant bacteria. In Evolution in Health and Disease. 2nd edition. Oxford University Press; 2008.


Per capita total antibiotic sales, 2005-2010 Per capita total antibiotic use, retail sector, 2005-2010 25000

Standard Units per 1000 population

20000

2005 15000

2006 2007 2008

10000

2009 2010

5000

0 BRAZIL, RETAIL

INDIA, RETAIL

Source: IMS Health Incorporated.: marketing research

VIETNAM, RETAIL

NORWAY, RETAIL

USA, RETAIL


Antimicrobial over-use: medical workers Antibiotic use for common cold, United States, 1997-2002


Antibiotic use: outpatient penicillin usage correlated with penicillin resistance, Europe, 2005

Source: Goossens, 2005


Antibiotic over-use: lack of simple diagnostics for human infections Patient complains of urethral discharge Urethral Discharge Examine: Milk urethra if necessary NO

NO Discharge confirmed? YES •Treat for gonorrhoea and chlamydia •Educate •Counsel if needed •Promote/provide condoms •Partner management •Return if necessary

Source: WHO 1997

Ulcers present?

•Educate •Counsel if needed •Promote/Provide condoms

YES Use appropriate flow chart


Penicillin resistant Gonorrhoea, 1990s

Source: WHO from published reports


Counterfeit Artesunate (53% of all sampled), Southeast Asia, 2006-2007

(A) Genuine (B) Sticker copy (C) Fake stamp (only visible under UV light) (D) Hologram copy Source: Newton PN,, et al. (2008). PLoS Med 5(2): 32:10.1371


P. falciparum parasitaemia 3 day

post treatment, artemisinin-based combination therapies (2006-2010)

Source: WHO/Roll Back Malaria Partnership


Antimicrobial use: mis-understanding by patients Malaira, chemoprophylaxis, 635 pregnant women, Malawi % with urine CQ metabolites compatible with intake preceding 7 days 45 40 35 30 25 20 15 10 5 0 History + Source: CDC

History -


Hand hygiene and hospital acquired infections, Australia, 2007

Source: Australia Clinical Excellence Commission, 2007


Antibiotic consumption in animals, 2005

Source: Agbioforum


Antibiotic use: use in plants, fish and animals US: OVER-USE OF ANTIBIOTICS THREATENS HUMANS by Danielle Knight Washington,11 Oct. (IPS) â&#x20AC;&#x201C; More than half of the antibiotics used in the United States are estimated to be used in animal feed for poultry, hogs, and cattle In 80 percent of cases, the drugs are used to fatten the animals faster. Between 40,000 and 50,000 pounds of tetracycline and streptomycin - both used to treat infections in humans - are sprayed to control bacterial disease among fruit trees. In the United States nearly 150 pounds of antibiotic are applied per acre of salmon Source: Inter Press Service


Multidrug-resistant Definitive Type (DT) 104 Salmonella Typhimurium, Europe, 1982-1996 Salmonella Typhimurium isolates from both cattle and humans cattle

humans

%

50 40 30

20 10 0 1982-85

1986-90

Source: WHO from published data

1991-94

1995-96


Failing research and development: 90/10 gap 10% health research by both public and private sectors devoted to health problems in developing countries OF WHICH

2%

is devoted to AIDS, TB, malaria, ARI, diarrhoeal diseases

Source: Global Forum for Health Research


Discovery of antibiotics: a faltering pipeline

Source: Wright G.. Nature Reviews Microbiology 5, 175-186 (March 2007)


Global Spread of ChloroquineResistant Strains of P. falciparum, 1950-1980

Source: Cell. 1997. Global spread of chloroquine-resistant strains of P. falciparum.


Spread of multi-resistant pneumococcus first identified in Spain, 1990s

Source: Klugmann, South African Institute of Medical Research


Carbapenamase-producing Enterobacteriaceae strains. Bangladesh, India, Pakistan and the UK, 2009

Source: Kumarasamy KK, et al Lancet ID, 2010


WHO Global strategy for containment of resistance, 2001


The five key areas for containment of antimicrobial resistance Rational drug use and regulation Infection prevention

Surveillance

Research and development

Clean animal husbandry, agriculture, aquaculture


Campaign to decrease antibiotic demand, Europe


Hospital Acquired Infections and antimicrobial resistance, 1993 - 2005

USA

Source: CDC, USA


European ban on use of antibiotic for animal growth promotion


700 000

60 000

600 000

50 000

500 000 400 000 30 000 300 000 20 000 200 000 10 000

100 000 0

0 1981

1984 1987 1990 1993 1996 1999 2002 Volume salmon and trout Consumption antibiotics

Source: FAO/OIE/WHO Expert consultation on antimicrobial use in aquaculture and antimicrobial resistance, 2006

Antibiotics

Volume

(tons wfe)

40 000

(kg active substance)

Antimicrobial use in Salmon and trout production in Norway


WHO - Patient Safety Programme Report on examples of containment


Antimicrobial resistance: the problem is global, the solutions are local


/dr_david_heymann  

http://www.cddep.org/sites/cddep.org/files/dr_david_heymann.pdf

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