Key Strategies for Improving Use of Existing and New Antibiotics

-the European Experience

Otto Cars

Professor Inf. Diseases, Uppsala University, Sweden

Chairman, ReAct – Action on Antibiotic Resistance www.reactgroup.org

What is the European Union?• 27 Member States

• 23 official languages

• > 500 million inhabitants(per country: 416,333 – 81.7 million)

• €25,100 GDP/capita (per country : 10,400 – 69,300)

• A patchwork of cultures!

1 € = 0.88 £ = 1.43 US$

No data

No awarenessNo priority

No funding

Antibiotic Resistance - the vicious circle

Key Strategies for Improving Use of Existing and New Antibiotics -the European Experience

Data

Awareness

National coordination

Interventions

Klebsiella pneumoniae : proportion of multidrug*-resistant invasive isolates resistant, 2010

Source: EARS-Net, 2011.

*Resistant tothird-generationcephalosporins, fluoroquinolones and aminoglycosides

European Antibiotic Resistance Surveillance: EARS-net

Source: European Surveillance of Antimicrobial Consumption (ESAC).

Outpatient antibiotic (J01) use, by antibiotic class according to ATC classification, 2009

Cyprus and Lithuania: total use, i.e. including inpatients.Spain: reimbursement data, i.e. not including over-the-counter sales without a prescription,

Gre

ece

Cypr

us*

Fran

ce

Italy

Luxe

mbo

urg

Belg

ium

Slov

akia

Pola

nd

Portu

gal

Mal

ta

Irela

nd

Lith

uani

a*

Spai

n**

Icel

and

Bulg

aria

Czec

h Re

pu...

Finl

and

Unite

d Ki

n...

Hung

ary

Denm

ark

Aust

ria

Norw

ay

Ger

man

y

Slov

enia

Swed

en

Neth

erla

nds

Esto

nia

Latv

ia

0

5

10

15

20

25

30

35

40Other J01 classes

Sulfonamides and trimethoprim (J01E)

Quinolones (J01M)

Macrolides, lincosamides and streptogramins (J01F)

Tetracyclines (J01A)

Cephalosporins and other beta-lactams (J01D)

Penicillins (J01C)

DDD

per 1

000

inha

bita

nts

and

per d

ay

U

K

Czec

h Re

p.

Source: ESAC, 2011.

European Surveillance of Antibiotic Consumption (ESAC)

Human burden

Economic burden

Burden of multidrug-resistant (MDR) bacteria in the EU, Iceland and Norway

Infections (6 most frequent MDR bacteria, 4 main types of infection) approx. 400,000 / yearAttributable deaths approx. 25,000 / yearExtra hospital days approx. 2.5 million / year

Extra in-hospital costs approx. € 900 million / year Productivity losses approx. € 600 million / year

SoLimitation: these are underestimatesSource: ECDC, 2009.In:http://ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time to_React.pdf

18 November 2011

http://antibiotic.ecdc.europa.eu

Images from national campaigns on prudent use of antibiotics

Council Recommendation on the prudent use of antimicrobial agents, 2001

Council Recommendation of 15 November 2001 on the prudent use of antimicrobial agents in human medicine (2002/77/EC)

Photo: Stuart Chalmers, CC-BY

Implementation of National Intersectoral Coordination Mechanisms on AMR

Adapted from: European Commission, Directorate - General Health and Consumers, 2010. http://ec.europa.eu/health/antimicrobial_resistance/key_documents/index_en.htm

As of 2008, 18 EU Member States and Norway had implemented an Intersectoral Coordination Mechanism

19871988

19891990

19911992

19931994

19951996

19971998

19992000

20012002

20032004

20052006

20072008

20090

200

400

600

800

1000

1200

1400

0 - 45-1415 - 6465 - 99

Rece

pt/

1000

invå

nare

och

år

Antibiotic presciptions/1000 in different age groups in Sweden

http://www.ameli.fr/fileadmin/user_upload/documents/DP_Antibiotiques_10-01-2008.pdf

Antibiotic Use by Age Group in France

0

10

20

30

40

50

60

% R

esis

tant

0

20

40

60

1990

2005

% R

esist

ant

S. pneumoniae, penicillin-non susceptible S. pneumoniae, erythomycin-resistant S. pyogenes, erythromycin-resistant

France Belgium

Source: French Nat. Ref. Ctr. for S. pneumoniae (Courtesy: E. Varon, L. Gutmann & B. Schlemmer) & Belgian Nat. Ref. Ctrs. for S. pneumoniae and for S. pyogenes (Courtesy: BAPCOC, H. Goossens)

Decreases in antimicrobial resistance following national media campaigns

Cathegory• Community aqcuired?

• Hospital acquired?

• Surgical prophylaxis?

Specific indication• Septicemia?

• Pneumonia?

• Wound infection?

• UTI?

Changing prescribing pattern in pneumonia through real time feedback (DDD defined daily dosages)

0500

100015002000250030003500400045005000

2007-Q1

2007-Q2

2007-Q3

2007-Q4

2008-Q1

2008-Q2

2008-Q3

2008-Q4

2009-Q1

2009-Q2

2009-Q3

2009-Q4

Cefuroxim+cefotaxim Penicillin G

Implementation of SAI

A user friendly system coupling prescriptions to

diagnosis in hospitals

We are facing a public health threat

AntibioticResistance

DrugDevelopment

MorbidityMortality

Costs

Is there a need to change the present market system ?

YES !

Innovative Incentives for Effective Antibacterials

A conference during the Swedish Presidency of the EU 2009 focusing on the need to reinvigorate research and development of new antibiotics

GovernmentsAcademiaPharmacuetical and biotech industryCivil society

Justifies intervention from the public sector

Urgent need for new antibiotics

Market failure

Impending health crisis

High health and economic burden from resistance

New collaborative models needed

Urgent need for new antibiotics

The overall innovative capacity is low

There are major scientific challenges

Who is going to do the work?Big Pharma? Small pharma? Academia?

But we cannot keep (mis)using them the way we have for the last 70 years!

Marketing and use needs to be restricted De-linking return of investment from sales !

We need a new business logic!

Urgent need for new antibiotics

From the EU Commission Action Plan on Antimicrobial Resistance launched TODAY in Brussels

Adapted from Källander, 2005

Access Excess

A new business model must be built on the global needsand secure access and affordability as well as rational use