1. 1 7th European Congress of Chemotherapy and Infection Florence - Italy, October 19-22, 2005 GPs in France, clinical evaluation and prescriptions in respiratory tract infections Pr Christian Chidiac Service des Maladies Infectieuses et Tropicales INSERM 0230 Hôpital de la Croix Rousse F69317 Lyon christian.chidiac@chu-lyon.fr

2. Mars 2000Les Outils de la Traçabilité2 ABT prescriptions in France Sources : EPPM - INSEE 100 120 140 160 180 200 220 19801982198419861988199019921994199619982000 Antibiotic prescriptions GPs French population

3. 3 ABT consumption EU - 2002 Utilisationantibiotiqueenvilleen Europe-2002 0 5 10 15 20 25 30 35 FRGRLUPTITBESKHRPLISIEESFIBGCZSISEHUNOUKDKDELVATEENL DDD per 1000 inh. per day Others J01B+J01G+J01X Sulfonamides and trimethoprim J01E Quinolones J01M Macrolides, Lincosam., Streptogramins J01F Tetracyclines J01A Cephalosporins J01D Penicillins J01C

4. 4 GermanyBelgiumSpainItalyFranceNetherland Upper resp infections36%42%41%33% 56% 33% Respiratory infections32% 21%25%28% Skin and soft tissu inf 3% 6%15%12% 5%7% UTI17% 9%13%18% 7%17% Miscellaneous12%11%10%12% 4%15% Source : IMS ABT Prescriptions in European coutries (2001)

5. 5 Review of main guidelines in France

6. 6 Common Cold

7. 7 Common cold Bacterial complication as acute otitis media, sinusitis Risk factors for bacterial complication Non-complicated common cold Non-complicated common cold and risk factors Common cold with bacterial complication Inform parents/patients of clinical signs indicative of bacterial complication* Symptomatic treatment Symptomatic treatment and follow up ABT treatment of the bacterial complication In case of secondary bacterial complication Investigate for

8. 8 Acute Otitis Media

9. 9 Purulent AOM OM with effusionRedness of tympanic membrane No ABT > 2 Years, mild symptoms No ABT treatment < 2 years, > 2 years, marked symptoms ABT treatment Symptomatic treatment Follow up 48-72 h Amoxicillin clavulanic acid or cefuroxime-axetil or cefpodoxime- proxetyl Contra-indication for betalactam : erythromycin-sulfafurazole pristinamycin

10. 10 Pharyngitis

11. 11 Clinical signs of pharyngitis Rapid Antigen Test Positive Negative ABT* Symptomatic treatment *Amoxicillin, Penicillin allergy : 2 nd, 3 rd G cephalosporin Contra-indication for betalactams : pristinamycin (> 6 y), macrolide, telithromycin

12. 12 Clinical signs of pharyngitis Rapid Antigen Test Positive Negative ABT*YesNoAcute rheumatic fever risk factors Symptomatic treatmentCulture Positive Negative *Amoxicillin, Penicillin allergy : 2 nd, 3 rd G cephalosporin Contra-indication for betalactams : pristinamycin (> 6 y), macrolide, telithromycin

13. 13 Acute sinusitis in adults

14. 14 Maxillary Frontal Fronto-Ethmoidal Sphenoidal Amoxicillin clavulanic acid, 2 nd and 3rd G cephalosporin (except cefixime) : cefuroxime-axetyl, cefpodoxime- proxetil, cefotiam-hexetil, Pristinamycin, telithromycin Failure of first line ABT : respiratory quinolone As above, or respiratory quinolone (levofloxacin, moxifloxacin) Acute sinusitis in adult

15. 15 Community-Acquired Pneumonia

16. 16 CAP : Healthy Adult Pneumococcal or atypical ? Pneumococcal (acute onset) Atypical (epidemic context, progressive onset) Oral amoxicillin 3g/d Failure Oral amoxicillin 3g/d Or telithromycin, or pristinamycin Macrolide, Telithromycin, Pristinamycin, Respiratory quinolone Failure Oral macrolide Failure Oral amoxicillin, Telithromycin, Pristinamycin, Respiratory quinolone Hospital if severity symptoms, Complication, or failure of 2 nd line ABT

17. 17 CAP : Adult with Risk Factors Failure Hospital Parenteral 3 rd G cephalosporin, Amoxicillin clavulanic acid, Respiratory quinolone Severity symptomsComplication

18. 18 Acute Exacerbation of COPD

19. 19 Classification of COPD Stage I, II, III : FEV 1 /FVC < 70%, Inconsistent chronic symptoms (cough, sputum production) Dyspnea at rest Stage III : severe COPD FEV 1 < 30% predicted or FEV 1 < 50% + hypoxemia < 60 mmHg Dyspnea of effort Stage II : Moderate COPD 50% ≤ FEV 1 < 80% predicted No dyspnea of effort Stage I : Mild COPD FEV1 ≥ 80% chronic symptoms : cough, sputum production No dyspnea of effort Stage 0 : FEV 1 /FVC > 70% predicted Associated Clinical signsSeverity upon spirometry

20. 20 COPD : at risk patients* One of the following characteristics FEV 1 < 30% at baseline Hypoxemia at baseline (< 60 mmHg [8 Kpa]) Frequent exacerbations (≥ 4/Year) Long term steroid treatment Comorbidity, underlying illness CAP history * Risk of : –Severe respiratory failure, –Underlying illness decompensation, –GNB infection (H. influenzae excluded)

21. 21 COPD Stage 0 and acute exacerbation –No antibiotic COPD Stage I, II, III and acute exacerbation –If marked purulence of sputum + dyspnea and/or increased volume of sputum –Presence of risk factors Antibiotic management of AECOPD

22. 22 Antibiotic management of AECOPD One risk factor* at least Yes *Dyspnea (or FEV 1 4 AECB / y, comorbidity, CAP history Yes Amoxicillin clavulanic acid, 2 nd G oral cephalosporin (cefuroxim) 3 rd G cephalosporin (cefpodoxime, cefotiam, ceftriaxone) Respiratory quinolone Failure : Sputum culture : Pseudomonas ? X-ray No Amoxicillin Macrolide Pristinamycin Telithromycin No Follow up No antibiotic Clinical worsening or Purulence of sputum Acute Exacerbation of COPD stage I, II, III Increased purulence of sputum + dyspnea and/or increased volume of sputum

23. 23 Controlling ABT prescriptions in France

24. 24 Controlling ABT prescriptions in France : History 1993 : « RMO » : French references 1996 : Antibiotics and resistance in hospital (Andem) 1998 : Observatory on use of ABT 1999 : Fight against bacterial resistance (InVS) 1999-02 : Official French Guidelines (Afssaps) 2001 : National Antibiotic Plan (B Kouchner, Health Minister) 2002 : Consensus conference : How to improve quality of ABT prescriptions ? (French Society for Infectious Diseases) 2002 : Ministerial circular : ABT referent doctors 2002 : French social insurance campaign

25. 25 French 1993 references « RMO » « Experts » from the French Social Security Focus on useless or dangerous prescriptions “It is not indicated to prescribe….” –Aminopenicillin and betalactamase inhibitor, 2 nd or 3 rd G cephalosporin –For no risk patients –Suffering of seasonal respiratory infections, pharyngitis, or CAP –Excluded : AOM, sinusitis, epiglottitis, bronchiolitis

26. 26 French 1993 references « RMO » : Results Angine Bronchite IPPM/IMS France Indication targeted by the « RMO » Indication not targeted by the « RMO » 0 10 20 30 40 50 60 70 80 P93A93P94A94P95A95P96A96P97A97 Acute Otitis Acute sinusitis RMO + 12 months RMO + 4 years RMO 0 10 20 30 40 50 60 70 80 P93A93P94A94P95A95P96A96P97A97 Pharyngitis Bronchitis % ABT RMO + 4 years RMO + 12 months RMO % ABT

27. 27 Prescription : impact of RMO and Drug Promotion 0 5 10 15 20 25 30 35 40 8587899193959799 '01 '03 Aminopenicillin R.M.O Amoxicillin price  0 5 10 15 20 25 30 35 40 8587899193959799 '01'03 Cephalosporins R.M.O 0 5 10 15 20 25 30 35 40 8587899193959799 '01'03 Macrolides R.M.O PrescriptionsDrug promotionLaunching new drug Sources : CAM, Dorema Generic Drug

28. 28 Prescription : Impact of RMO and Drug Promotion 0 5 10 15 20 25 87899193959799 '01 '03 BL Inhibitors R.M.O 0 5 10 15 20 25 87899193959799 '01 '03 C2G / C3G R.M.O 0 5 10 15 20 25 87899193959799 '01'03 Quinolones R.M.O PrescriptionsDrug promotionLaunching new drug Sources : CAM, Dorema

29. 29 French National ABT Campaign General Public… –Television vidéo clips, radio, newspapers, magazines Medical Doctors… –Rapid Antigen Test for pharyngitis, formation –Therapeutic forms –Individual medical interview –Transmission of consumption information Childhood professionals, parents… –Information, education, meetings Patients… –Documentations, information ABT risks, resistance…

30. 30 ABT prescriptions since 1980 in France Source : EPPM 100 110 120 130 140 150 160 170 180 190 200 210 220 19801981198219831984198519861987198819891990199119921993199419951996199719981999200020012002 BASE 100 = 1980 (#) (RMO) (#) (#) = Epidemy (#) Plan CNAMTS (#)

31. 31 Source : DOREMA CMA 0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 80818283848586878889909192939495969798990001020304 CephalosporinsAminopenicillinMacrolide + TelithromycinBL inhQuinolone (%) « RMO » AMP CEPH MAC + TEL BL INH FQ ABT consumption in France

32. 32 First Results : drop in prescriptions Mean drop : -10,2 % 4,1 millions of prescriptions -5,4 % 1,9 millions of prescriptions En millions de prescriptions D. Guillemot, CERBEP, Institut Pasteur - CNAMTS 34,7 40,7 M 38,8 M 36,6 M 30 32 34 36 38 40 42 2000-20012001-20022002-20032003-2004

33. 33 ABT consumption by age Since 2002,  23,1% < 15 years  20,6% 0- 5 years D. Guillemot, CERBEP, Institut Pasteur - CNAMTS 0 0,5 1 1,5 2 2,5 3 123456-1011- 15 16- 20 21- 25 26- 30 31- 35 36- 40 41- 45 46- 50 51- 55 56- 60 61- 65 66- 70 71- 75 76- 80 81- 85 86- 90 et + Age (years) Consumption by 6 months/inhabitant winter 2001-2002winter 2002-2003winter 2003-2004 -0,5 -0,6 -0,3

34. 34 ABT prescriptions in respiratory infections 1995-2004 Sinusite CIM 10 Otite Bronchite Prescriptions/100 visits Pharyngite Source : EPPM 15 25 35 45 55 65 75 85 95 105 1995 (été) 199619971998199920002001200220032004 Tonsillitis Rhinopharyngitis Bronchitis Acute Otitis Sinusitis CIM 9 Sinusitis CIM 10 Pharyngitis

35. 35 ABT treatment prescribed by GPs for CAP 1 No risk factor*Risk factor*total ‡ Amoxicillin181331 Amoxicillin clavulanate71017 Cephalosporin IV/IM189 Cephalosporin (oral)6410 Macrolide4711 Quinolone437 Other monotherapy2027 Combination527 total47 94 * > 65 yr or comorbid illness or underlying disease Fantin B Chest 2001;120:185-192 ‡ p = 0.33

36. 36 ABT treatment prescribed by GPs for CAP 2 No risk factors Risk factors total ‡ In agreement with guidelines22 (47%)16 (34%)38 (40) Not in agreement with guidelines25 (53%)31 (66%)56 (60%) Total, N°47 94 Pts without risk factor = amoxicillin or macrolide Pts with risk factors = amoxicillin clavulanate, or oral cephalosporin ± macrolide or quinolone Fantin B Chest 2001;120:185-192 ‡ p < 0.5

37. 37 Conclusion “Now, HERE, you see, it takes all the running YOU can do, to keep in the same place” Alice’s adventures trough the looking glass. L. Caroll