résistance aux antibiotiques:la prochaine pandémie dr jean carlet réanimateur teinté...
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Résistance aux antibiotiques:la Résistance aux antibiotiques:la prochaine pandémieprochaine pandémie
Dr Jean CARLETRéanimateur teinté d’infectiologieAncien president du CTIN(National Committee for Prevention of Nosocomial Infections)N’a fait que passer à la HASConsultant pour l’OMS
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THERE ARE SOME VERY GOOD THERE ARE SOME VERY GOOD NEWSNEWS
Efficacy of most programs against MRSA ( France, Belgium, Denmark, UK, USA…)
Efficacy of some national campaigns aimed at reducing antibiotic consumption (France, Belgium, Scotland, South Korea, Japan..)
Efficacy against carbapenemases ( Israel, Poland), VRE (France)
Strong international « reaction » to resistance ( ECDC, IDSA, TATFAR…)
Lobbying groups: ACdeBMR, React, AB action, APUA ….Reasearch programs ( Mosar…)Quality indicators
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Courtesy: Grundmann et al. (EARSS, Sept 2009) and Harbarth for Sarkoleon
MRSA bacteremia in Europe, 2008
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Taux annuels SARM acquis pour 100 patients Taux annuels SARM acquis pour 100 patients admis plus de 24 heures : portage sur tout site admis plus de 24 heures : portage sur tout site et bactériémies et bactériémies
0,940,99
0,73
0,65
0,440,29
0,062
0,073
0,062
0,023
0,015
0,113
0
0,2
0,4
0,6
0,8
1
1,2
1999 2000 2001 2002 2003 2004
0
0,02
0,04
0,06
0,08
0,1
0,12
SARM acquis tout site/100 admisbactériémies à SARM acquises/100 admis
% %
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Counts of MRSA bacteraemia Counts of MRSA bacteraemia
Oct 2005 to June 2009Oct 2005 to June 2009
0
200
400
600
800
1000
1200
1400
1600
1800
2000
Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2
2005 2006 2007 2008 2009
Counts of MRSA bacteraemia
Ye
ar
an
d q
ua
rte
r
* DATA ARE PROVISIONAL NOT FOR WIDER CIRCULATION
BBC World news
Courtesy: A. Pearson and colleagues (HPA, Sept 2009)
MR
SA
BS
I ep
isod
es
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29,4
26,2525,15
23,9523,09
6,96
10,06
17,5
18,99
0,130,11
0,230,330,29
0,44
0,650,73
0,99
0
4
8
12
16
20
24
28
32
2000 2001 2002 2003 2004 2005 2006 2007 2008
0
0,2
0,4
0,6
0,8
1
1,2
Consommation de SHA année 2008
Taux de SARM acquis (novembre 2008)
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0,5
0,7
0,9
1,1
1,3
1,5
1,7
1,9
2,1
2,3
1 2 3 4 5 6 7 8 9 10 11
0
1
2
3
4
5
6
7
8
QUINOLONES
MRSA per 1000 pat-days
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Antibiotic use : specific classes
0
20
40
60
80
100
120
1999 2000 2001 2002 2003 2004 2005
Year
DD
D/1
,000
pat
ient
-day
s
Quinolones 3rdG Cephalosporins Glycopeptides
p = 0.01
p;: 0.03NS.
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P. aeruginosa P. aeruginosa : ICU St Joseph hospital: ICU St Joseph hospital
Résistance toCiprofloxacineRésistance toCiprofloxacine
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P. aeruginosa P. aeruginosa :ICU St Joseph :ICU St Joseph
Résistance to AmikacineRésistance to Amikacine
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0
10
20
30
40
50
60
70
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
%
Années
St JOSEPH E. coli : Résistance (I+R)
Ampicilline
Amox / Clav
Pip / Tazo
Cefotaxime
Gentamicine
Ac. Nalidixique
Ciprofloxacine
TMP
Sulfamide
I
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2005-2008 program: Politicians want a 2005-2008 program: Politicians want a public reporting of nosocomial infections public reporting of nosocomial infections rates. Quality Indicators selected rates. Quality Indicators selected
Composite indicator using data from annual mandatory report of Infection Control committees ( started in 2005: ICALIN):1st to be released
Consumption of alcohol based handrub: Nb of liters/1000 hosp days
Surgical site infection (SSI) rate: probably not very controversial topic.The indicator is yes or no, and % of units participating in a given hospital
Meticillin-resistant Staphylococcus aureus (MRSA) rate: Nb of MRSA/1000 hospital days + trends ,,
Antibiotic consumption ICATB: process indicator for AB usage in hospitals
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Monthly notifications received at the InVS, Monthly notifications received at the InVS, France, 01/08/2001 to 31/12/2007 (N=5,357)France, 01/08/2001 to 31/12/2007 (N=5,357)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
août
-01
oct-0
1
déc-
01
févr
-02
avr-0
2
juin
-02
août
-02
oct-0
2
déc-
02
févr
-03
avr-0
3
juin
-03
août
-03
oct-0
3
déc-
03
févr
-04
avr-0
4
juin
-04
août
-04
oct-0
4
déc-
04
févr
-05
avr-0
5
juin
-05
août
-05
oct-0
5
déc-
05
févr
-06
avr-0
6
juin
-06
août
-06
oct-0
6
déc-
06
févr
-07
avr-0
7
juin
-07
août
-07
oct-0
7
déc-
07
Month of notification
Not
ifica
tions
(N)
+20% p.year+20% p.yearMedian delay: 9 days
c. 30% HCF have notified at least once
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ABT prescriptions from 2001-02 to 2006-07ABT prescriptions from 2001-02 to 2006-07(Oct-March periods) Guillemot et al PLOS medicine 2009(Oct-March periods) Guillemot et al PLOS medicine 2009
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French Campaigns 2002-2007French Campaigns 2002-2007Outpatient antibiotic use in France in prescriptions Outpatient antibiotic use in France in prescriptions per inhabitant – October to Marchper inhabitant – October to March
Sabuncu et al., PloS Medicine; June 2009
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Belgian Campaigns 2002-2010 Outpatient antibiotic use in Belgium in packages
per 1,000 inhabitants per day – July – June
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Belgian National Belgian National Public CampaignsPublic Campaigns
When: since November 2000, annually during winter season Organised by: BAPCOC (Belgian Antibiotic Policy
Coordination Committee) Budget:
◦ 400,000 EUR/annual campaign Interventions targeting the public:
◦ Ads on TV, radio and newspaper ◦ Information booklets◦ Folders ◦ Posters◦ Internet campaigns: www.antibiotics-info.be
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Results Scotland – Results Scotland – Empirical PrescribingEmpirical Prescribing
National compliance 93% and 7/14 NHS boards achieved target
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Results Scotland – Results Scotland – Empirical PrescribingEmpirical Prescribing
National compliance 83% and 4/14 NHS boards achieved target 2011 - need to focus on improvement
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18 November 2
008
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Why is Europe (partially) Why is Europe (partially) successful?successful?
Bottom up Member States initiatives (e.g. rotating European presidencies) resulting in top down political support and commitment at European level (e.g. surveillance programme);
Strong leadership with close link between opinion leaders, policy makers and politicians
European antibiotic awareness day, built on success stories of countries;
Support of AMR research projects by EC, providing evidence for public health interventions
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DG Research funded projectsDG Research funded projects
ARPACArMEDPARGRACEMOSARCHAMPInTopSensTheraEDGETEMPOtest
SATURNHAPPY AUDITR-GNOSISEvoTAR………
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BAD NEWS, UnfortunatelyBAD NEWS, Unfortunately
Some negative experience
ESBL increases, in humans, animals, water, soil !!!
New mechanims of resistance (NDM-1, Oxa-48)
Extremely high levels of resistance in several countries, very close to us !!
Asia, Africa ??
NO new antibiotic active against Gram negatives in the pipe ( anti ESBL ?)
Poor investement of the industry
No moneyDiagnostic tests
poorly usedEducation poorly
effective.53% of consumers : AB work on viruses
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Negative or poorly positive Negative or poorly positive trialstrials
Negative trials in England or the US Recent increase in consumption in FranceRCT in primary medicine Butler BMJ 2012
34 practices vs 34 controls139 clinicians vs 124 controlsSTAR program: practice based seminar,
analysis of practices, outline education,practising consulting skills
Reduction in AB consumption: 4% !Reduction in cost: 830 pounds per practice
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0,00
0,05
0,10
0,15
0,20
0,25
0,30
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
année
den
sité
d'in
cid
ence
(10
00jh
)
incidence E.coli BLSEincidence K.pneumoniae BLSEincidence E.cloacae BLSEincidence autres entérobact. BLSE
Vincent Jarlier Sept 2009
Rate of incidence (/1,000DHs) of different species of ESBL enterobacteria
38 Univ. hospitals of Paris area 1996-2008
2002 K.pneumoniae
E.coli
E. cloacae
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Assistance publique Paris. Incidence Assistance publique Paris. Incidence of MRSA ( Pink) and ESBL ( green)of MRSA ( Pink) and ESBL ( green)
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Community-onset bacteremia Community-onset bacteremia due due to ESBL E coli.to ESBL E coli. Rodriguez-BanoRodriguez-Bano CID 2010CID 2010
95 cases of E coli with ESBL ( 7.3%) From Oct 2004 to Jan 2006 87% were CTX-M Risk factors: contact with healthcare,
urinary cath, previous AB Inappropriate AB correlated with ESBL,
and with mortality
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Success with MRSA…..failure with Success with MRSA…..failure with ESBLs….WHY ??ESBLs….WHY ??
Low inoculum for MRSA high with ESBL Skin, nose for MRSA, GUT for ESBL Selection in the gut with antibiotics Transmission in the community ( 6% of
healthy carriers, MH Nicolas-Chanoine ICAAC 2011)
ESBLs in food animals. 90% of the sampled chicken Overdevest EID 2011
ESBLs in water, both used and drinking ( Recent study in India)
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Vatopoulos A. Eurosurveiillance 2008
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Klebsiella pneumoniae resistant Klebsiella pneumoniae resistant to carbapenems. EARS-net ECDC to carbapenems. EARS-net ECDC 20102010
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Pseudomonas aeruginosa resistant to Pseudomonas aeruginosa resistant to carbapenems. EARSS-net ECDC 2010carbapenems. EARSS-net ECDC 2010
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Eurobact study Tabah A, Timsit JF Eurobact study Tabah A, Timsit JF 20 most frequent pathogens during 20 most frequent pathogens during bacteremiabacteremia
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Current Status Current Status of Antimicrobial Resistance in Asiaof Antimicrobial Resistance in Asia
1st APEC Expert Forum 34
MRSA
Korea
Japan
HK
Taiwan
Sri Lanka
Vietnam
India
Saudi Arabia
Thailand
Philippines
Singapore
Malaysia
China
Indonesia
< 1 %
5-10 %
10-25 %
25-50 %
> 50 %
1-5 %
unknown
Resistance %
Korea >50%
Japan >50%
China >50%
Hong Kong 25-50%
Taiwan >50%
Philippines 25-50%
Thailand 25-50%
Vietnam >50%
Malaysia 10-25%
Singapore 25-50%
Indonesia 10-25%
India 25-50%
Sri Lanka >50%
Saudi Arabia 25-50%
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(49/377)
(270/574)
(93/97)
(654/147)
(147/705)
(82/345) (46/93)
(122/316)
Distribution of MRSA by Distribution of MRSA by CountryCountry2004-6, CA-MRSA and HA-MRSA, 2004-6, CA-MRSA and HA-MRSA, Asia
%
No. of isolates
(CA-SA,HA-SA)
CA-MRSA
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ESBL-producing E. coli
Korea
Japan
HK
Taiwan
Sri Lanka
Vietnam
India
Saudi Arabia
Thailand
Philippines
Singapore
Malaysia
China
Indonesia
1st APEC Expert Forum
< 1 %
5-10 %
10-25 %
25-50 %
> 50 %
1-5 %
unknown
Resistance %
Korea 10-25%
Japan 10-25%
China >50%
Hong Kong 25-50%
Taiwan 10-25%
Philippines 10-25%
Thailand 25-50%
Vietnam >50%
Malaysia 10-25%
Singapore 25-50%
Indonesia 25-50%
India >50%
Sri Lanka ?
Saudi Arabia 25-50%
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Carbapenem R Enterobacteriaceae
Korea
Japan
HK
Taiwan
Sri Lanka
Vietnam
India
Saudi Arabia
Thailand
Philippines
Singapore
Malaysia
China*
Indonesia
1st APEC Expert Forum
< 1 %
5-10 %
10-25 %
25-50 %
> 50 %
1-5 %
unknown
Resistance
rate
Korea <1%
Japan 5-10%
China 1-5%
Hong Kong <1%
Taiwan 1-5%
Philippines 1-5%
Thailand <1%
Vietnam <1%
Malaysia
Singapore 1-5%
Indonesia 1-5%
India 5-10%
Sri Lanka
Saudi Arabia <1%
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MDR A. baumannii
Korea
Japan
HK
Taiwan
Sri Lanka
Vietnam
India
Saudi Arabia
Thailand
Philippines
Singapore
Malaysia
China*
Indonesia
1st APEC Expert Forum
< 1 %
5-10 %
10-25 %
25-50 %
> 50 %
1-5 %
unknown
Resistance rate
Korea 10-25%
Japan <1%
China 25-50%
Hong Kong
25-50%
Taiwan 25-50%
Philippines
10-25%
Thailand >50%
Vietnam >50%
Singapore >50%
Indonesia 5-10%
India 25-50%
Saudi Arabia
10-25%
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Total outpatient antibiotic use (J01), 32 Total outpatient antibiotic use (J01), 32 countries, 2009countries, 2009
41
* Cyprus, Lithuania: total use, including the hospital sector.** Spain: reimbursement data, does not include over-the-counter sales without prescription.
10.2 DID
38.6 DID
28.7%66.0%
Median=19.0 DID
25.5%
0.2%
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Grave et al., J Antimicrobial Chemotherapy, 2010, 65, 2037-2040.
Criticised for not taking into account
• Differences in dosing between the various substances
• All animals species at risk of being treated (e.g. horses, sheep and goat)
• Biomass animals transported to other countries for fattening or slaughter
10 fold differences
Pre ESVAC data. Published sales data retrieved from national reports for 2007 (Germany 2005) and normalized for biomass at risk
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Can we stop ESBL outbreak ?Can we stop ESBL outbreak ? ESBL is now endemic: difficult task Infection control in hospitals: upgraded
standard precautions or isolation Screening of at risk patients: difficult Hygiene in the community: change some
habits to prevent fecal transmission: kids Treat hospital and animal farms effluents
to kill MDRO, and to neutralize antibiotics Stop treating animals with AB as groth
factors Decrease AB usage in therapy, and
prophylaxis of animals
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Containement of a country-wide Containement of a country-wide outbreak of carbapenem-resistant K outbreak of carbapenem-resistant K pneumoniae Schwaber CID 2011pneumoniae Schwaber CID 2011
2007 national program by ministry healthGuidelines, with detection of carriers
( screening), and dedicated staffingRessources for an extensive audit of IC
practicesFeed back to hospital directorsDuration:One yearOutcome: nosocomial cases of CRE
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Schwaber MJ et al Foll….Schwaber MJ et al Foll….
Before march 2007: 1275 cases in 27 hospitals ( 175/Million inhabitants)
Mortality before: 55.5 % per 100.000 patients days
Intervention led to a sharp decrease in the Nb of cases ( 11.7/ 100.000 Pts days)
Correlation between the number of cases and compliance to the guidelines (P:.02)
Beau travail, exportablePeu différent des mesures pour VRE
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One hospital’s experience –moving from single room contact to cohorting and dedicated staff
0
2
4
6
8
10
12
14
16
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
TIME (weeks)
NO. OF CASES
Implementation of guidelines
LAG TIME
Incidence of KPC-producing Klebsiella spp.
P=0.01
Schechner V, unpublished
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Focusing on carbapenemases ???Focusing on carbapenemases ???
Looks more easy Screening, isolation, destruction of the
bug in the gut ….but ESBL outbreak will induce a
dramatic increase in carbapenem usage, and the incidence of carbapenemases will uncrease quickly
A global program against both MRSA, VRE, ESBL and carbap is mandatory, but it is a lot of energy
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Cost of antibiotic resistanceCost of antibiotic resistance
25.000 deaths in Europe per year ( ECDC)MRSA USA: 90.000 infections. 19.000
deaths.1.5 billion euros in Europe ??20 billion USD in the States ??
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Ready for a world without Ready for a world without antibiotics ?? The Pensières antibiotics ?? The Pensières antibiotic resistance call to actionantibiotic resistance call to action
Organized by Biomerrieux2 days meeting of 70 international expertsVery active meeting, an disposal of 33
posters from 33 countriesQuestionnaire on the privilaged actions for
reducing resistancePublication: Special issue of Antimicrobial
resistance and Infection control February 2012
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Actions directed toward Health Actions directed toward Health autoritiesautorities
Reserve the most important classes of antibiotics for humans 66%
Stop over-the-counter sales of AB 51%Make the proposal to WHO to develop a
chart to be signed by all ministries of health worlwide ( including access to Ab, Infection control, and vaccines 51%
Change the re-imbursement system, rewarding the appropriate usage of Ab, for HCP and pharma companies 36%
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Message to the Health care Message to the Health care communitycommunity
Establish standardized, timely, universal surveillance of Ab resistance and consumption 82% of the 70 participants
Educate on AB stewardship and AB resistance, using modern tools 75%
Develop culturally sensitive awaireness campaigns for HCP 49%
Provide public with indicators of HAI 36%Avoid usage of quinolones 15% only
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Messages to the general Messages to the general publicpublic
Develop culturally sensitive awaireness campaigns targetted to general pub 75%
Develop sanitation and hygiene education 72%
Include consumers among stakeholders for AB resistance control, including the food chain 51%
Balance cost and benefit of antibioic free food 15…only
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Messages to the industry Messages to the industry ( pharma, food, diagnostics( pharma, food, diagnosticsfarming/bio-industry)farming/bio-industry)
Develop bedside and rapid testing to better guide AB treatment decisions 63%
Banish the use of antibioics as groth promoters in animal food 60%
Develop new antibiotics 57%Develop alternatives to antibiotics 46%
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V. Jarlier 28.6.2011
ATB stewardship
ATB stewardship + Infection control
Infection control
Survey (ATB, HAI)
PRONALIN POST/STOP Panafrican initiatives
MDR-TB control MDRO
surveyATB stewardship R
ATB stewardship
C
ATB stewardship + Infection
control MRSA
Infection control
MRSA
ATB stewardship + Infection control
C MRSA
Infection control
ATB stewardship + Infection control MRSA, VRE
Infection control MRSA
Infection control CRE
HAI survey
Survey MDRO in
environment MDRO survey
International action
Notification of threats WHO
MDRO survey Gulf corp. council
countries
MDRO survey
ATB stewardship C
ATB, HAI surveys Panamerican HO
ALCIS
MDRO survey
ATB stewardship R P.aeruginosa
ATB stewardship
C
Infection control MRSA
C: ATB consumption ; R: resistance
Infection control CRE
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World Alliance Against World Alliance Against Multiple-Drug-Resistant Multiple-Drug-Resistant Organisms (WAAMDRO)Organisms (WAAMDRO)
Created on april 7th 2011 ( Lancet Paper) International ( initially french) 345 participants Supported by 50 societies/ prof bodies Multi-professionnal ( MDs, veterinaries,
pharmacists, environnement specialists, deputees)
Multi-disciplinary Active participation of consumers ( Lien, Ciss,
Patients for patient safety WHO)
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OBJECTIVESOBJECTIVES
The main objective is the ACTIVE PROTECTION of antibiotics
The bacterial world must be respected (peace with microbes SB Levy)
Antibiotics: « special » drugs, with specific modalities of prescription
Antibiotic referent Different ABs in humans and animals ABs must belong to the UNESCO
mondial patrimony
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Quelles modalités de prescription Quelles modalités de prescription Pour la villePour la ville
Ordonnance spécifique, type carnet à souche pour toxiques: NON
Diagnostic présumé indiqué sur l’ordonnance. Pb confidentialité ?
Durée de traitementRé-évaluation systématique à J 2/3( coup de
fil, e-mail, consultation si sévèreQuantités exactes délivrées par le
pharmacien ( déconditionnement)Travail en réseau ville/hôpital
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Modalités de prescription à Modalités de prescription à l’hôpitall’hôpital
Rôle du référent bien identifié. Décret ++Diagnostic présumé mentionné sur
l’ordonnance, et dans le dossierDurée présumée de traitement indiquéeListe d’antibiotiques protégés, ne pouvant
être prescris que par un spécialiste/référentPremières doses ( 48 h) libresRé-évaluation systématique à J2/3Travail en réseau ville/hôpital
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OBJECTIVES Fol..OBJECTIVES Fol..
Develop antibiotic stewardship programs worldwide
Access to Abs to developping countries Upgrade infection control ( HRAS) Develop rapid diagnostic testing. DO NOT treat non bacterial infections Vaccination programs Accelerate the developpement of new
compounds Anti-virulence agents, non AB agents
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ACTIONSACTIONS
Participation to meetings ( french parliament, academy of medicine)
Contacts with HAS, AFSSAPS, DGS,ANSES Papers, citations The Barcelona declaration Involvement of consumers ( garance Upham) International action, in cooperation with
React, Antibiotic action, APUA… Contacs with WHO
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Le Point 12 janvier 2006