New German guidelines

Transcription

1 CAPNETZ-Symposium: Community-acquired pneumoniae New German guidelines S3-Guideline of PEG, DGP, DGI and CAPNETZ Höffken G 1, Lorenz J 2, Kern W 3, Welte T 4, Bauer T, Dahlhoff C, Dietrich E, Ewig S, Gastmeier P, Grabein B, Halle E, Kolditz M, Marre R, Sitter H. Paul-Ehrlich-Society for Chemotherapy 1, German Society for Pneumology 2, German Society for Infectiology 3, Competence-Network CAPNETZ Germany 4, Association of the Scientific Medical Societies in Germany

2 German CAP guideline S3-guideline acc. to the Association of the Scientific Medical Societies in Germany AWMF Consensus finding Evidence-based medicine Formulation of clinical algorythms Decision analysis Outcome analysis (in preparation with Competence network CAPNETZ, Federal Agency for Quality Control BQS) All mayor scientific societies incorporated No financing by pharmaceutical companies

3 Classification of evidence (Centre of Evidence Based Medicine 1999) Recommendation Evidence Description A B 1a 1b 1c 2a 2b 2c 3a 3b Evidence by systematic review of sound RCT Evidence by one appropriate RCT Anything-or nothing principle Evidence by systematic review of cohrit studies Evidence by one cohort study /RCT intermediate quality Evidence by outcome-research-studie Evidence by systematic review of case-control-studies Evidence by one case-control-study C 4 Evidence by case series/cohort studies and casecontrol studies of intermediate quality D 5 Expert opinion, laboratory results

4 Targets and target groups Targets Standards for diagnosis and therapy of LRTI Rational prescription of antimcrobials To reduce not indicated usage To avoid the extensive usage of specific antibiotic classes To avoid the emergence of resistant strains Critical review of microbiologic diagnostics Risk stratification Risk-adapted antimicrobial therapy Best clinical outcome and cost effectiveness

5 Principle structure of the guideline on community-acquired pneumonia and lower respiratory tract infections

6 Risk stratification

7 CAPNETZ Mortality figures according different scoring systems CURB CRB CRB-65 Mortality (%) Number positive criteria CAPNETZ 2005

8 Validation of matsr Prediction of mortality Rule Sensitivity Specifity PPW NPW matsr 94% 93% 49% 99,5% mbtsr 51% 80% 16% 96% Ewig S et al. Thorax 2004

9 Decision making for risk stratification Outpatient at the GP CRB-65: one positive criterion: consider hospital admission Inpatient at the emergency room mats score: If positive: consider ICU admission mats negative: CURB B If 1 positive criteria: consider ICU admission B

10 Diagnostics microbiological tests

11 Blood cultures (%) Blood culture + Change of Tx PSI 1 PSI 2 PSI 3 PSI 4 PSI 5 Waterer GW et al. Resp Med 2001; 95: 78 Outpatient setting: No blood cultures B Hospital: Optional blood cultures in mild to moderate CAP Mandatory blood cultures in the ICU B B

12 Sputum Accuracy and practicability in CAP Culture positive sputum 10/116 (9%) Culture guided therapy - all 1/116 (1%) - microscopic valide sputum 1/23 (4%) False positive rate of purulent sputum 14/19 (74%) Ewig Chest 2002; 121: 1486 Outpatient setting: no sputum testing A Hospital setting: sputum testing, if quality criteria fulfilled B

13 Serology and antigen testing No recommendation M. pneumoniae serology C. pneumoniae serology For all amplification assays Pneumococcal antigen test (to be revisited) Procalcitonin i.s. (to be revisited) Recommendation for antigen testing Legionella antigen-test in urine (2c) B B

14 Modifying factors for defining subgroups with different spectra of pathogens

15 CAP-spectrum of causative pathogens Lit. Höffken et al. Chemotherapie-Journal 2005; 14 mild moderate severe S. pneumoniae 38 (30-49) 27 (15-48) 28 (20-31) M. pneumoniae 8 (ng 13) 5 (2-9) 2 (0 3) H. influenzae 13 (4-22) 6 (0 7) 7 (0 10) C. pneumoniae 21 (0-32) 11 (0-17) 4 (0-7) S. aureus 2 (0-2) 3 (0-4) 9 (0-22) Enterobacteriaceae 0 4 (1-8) 9 (2-18) P. aeruginosa 1 3 (0-4) 4 (0-5) L. pneumophila 0 4 (0-8) 12 (0-23) Polymicrobial infection up to 27%, unknown aup to 50%

16 Dichotomy Mild outpatient CAP Risk (y/n) Comorbidities, advanced age, antibiotic pretreatment, recent medical contact Yes: Spectrum with less atypicals, more enterobacteria (2c) A Moderate and severe in-patient CAP Risk for P. aeruginosa (y/n) Pulmonary comorbidity, recent hospital discharge Yes: Spectrum with more enterobacteriaceae and P. aeruginosa (2c) A

17 Empirical treatment with ß- lactam-antibiotics and macrolides in the era of pneumococcal resistance

18 Actual resistance rates in Germany for pneumococci PEG statistics on resistance 2004 Penicillin G 1,2% ( 2 mg/l) Erythromycin DIN 11,3 % ( 8mg/l) CLSI 18,1% ( 1 mg/l) Doxycycline 8,2% No restriction to aminopencillines and macrolides in the empirical treatment of CAP B

19 A International Prospective Study of Pneumococcal Bacteremia: Correlation with In Vitro Resistance, Antibiotics Administered, and Clinical Outcome. YU VL et al. CID 2003; 37: 230

20 A International Prospective Study of Pneumococcal Bacteremia: Correlation with In Vitro Resistance, Antibiotics Administered, and Clinical Outcome. YU VL et al. CID 2003; 37: 230

21 Failure of Macrolide Antibiotic Treatment in Patients with Bacteremia Due to Erythromycin-Resistant Streptococcus pneumoniae John R. Lonks, 1 et al. CID 2002; 35: (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P = ). 5 (24%) of 21 case patients with the low-level resistant M phenotype and none of 40 controls were taking a macrolide (P =.00157).

22 ß-lactams versus macrolides any preferences in empiric therapy for mild to moderate CAP?

23 Clinical success Mild to moderate CAP n=6.749 Superiority for antibiotics with activity against atypicals Superiority for antibiotics without activity against atypicals

24 Outpatient therapy in mild CAP without risk factors A Compound Dosage (per d) Duration First choice Aminopenicilline - Amoxicillin 70 kg 3 x 1,0 g 7 10 d < 70 kg 3, 0,75 g Alternatives - Azithromycin 1 x 500 mg 3 d - Clarithomycin 2 x 0,5 3d / 0,25 g 7 10 d - Roxithromycin 1 x 300 mg 7 10 d oder - Doxycycline 1 x 200 mg / 100mg 7 10 d

25 Outpatient therapy in mild CAP with risk factors A Compound Dosage (per d) Duration First choice Aminopenicilline - Amoxicillin/ 70 kg 3 x 1,0 g 7 10 d clavulanate < 70 kg 2 x 1 g - Sultamicillin 3 x 0,75 g 7 10 d Alternatives - Levofloxacin 1 x 0,5 g 7 10 d - Moxifloxacin 1 x 0,4 g 7 10 d - Cefpodoxim- 2 x 0,2 g 7 10 d Proxetil - Cefuroxim-Axetil 2 x 0,5 g 7 10 d

26 Outpatient management of CAP recommendation A, evidence 4 Safe home care Clinical follow-up after h Stable oxygenation Stable hemodynamics Safe intake of medication In any suspicion: hospital admission

27 ß-lactam macrolide combination

28 Dual therapy including macrolides on mortality, LOS/charges Brown et al. Chest 2003; 123: 1503 Risk group C LOS (d) Death (%) Charges ($) Risk class D LOS (d) Death (%) Charges ($) ß-Lactam Mono ß-Lactam + macrolide n= ,38 7, n= , n= * 4,1* 8.601* n= ,24* 9.917

29 Not critically ill Baddour AJRCCM 2004

30 Critically ill Baddour AJRCCM 2004

31 Inpatient therapy in moderate CAP without risk factors for P. aeruginosa Compound Dosage (per d) Duration Aminopenicilline -- Amoxicillin/ clavulanate 3 x 2,2 g iv 7 10 d A -- Sultamicillin 3 x 3,0 g iv 7 10 d -- Cefuroxim-Axetil 3 x 1,5 g iv 7 10 d -- Ceftriaxone 1 x 2,0 g iv 7-10 d -- Cefotaxime 3 x 2,0 g iv 7-10 d -plus/minus Macrolide Fluoroquinolone -Levofloxacin 1 x 0,5 g iv 7 10 d -Moxifloxacin 1 x 0,4 g iv 7 10 d

32 Inpatient therapy in moderate CAP with risk factors for P. aeruginosa A Compound Dosage (per d) Duration Anti-pseudomonal ß-lactam -- Piperacillin/ Tazobactam 3 x 4,5 g iv 7 10 d -- Cefepime 3 x 2,0 g iv 7 10 d -- Imipenem 3 x 1,0 g iv 7 10 d -- Meropenem 1 x 1,0 g iv 7-10 d -- Cefotaxime 3 x 2,0 g iv 7-10 d -plus/minus Macrolide or Fluoroquinolone - Levofloxacin 2 x 0,5 g iv 7 10 d - Ciprofloxacin plus gram+ coverage 3 x 0,4 g iv 7 10 d

33 Combination therapy in patients with severe CAP

34 Mono- vs combination- ABT (ß-lactam plus/minus aminoglycoside) M Paul et al. BMJ 2004; 328: Same ß-Lactam clinical efficay any ß-Lactam tolerability

35 Combination Antimicrobial Therapy in P. aeruginosa Bacteremia inadequate empiric ABT adequate empiric Mono- ABT adequate empiric Combi- ABT Chamot E et l. AAC 2003; 2756

36 Inpatient therapy in severe CAP without risk factors for P. aeruginosa A Compound Dosage (per d) Duration Anti-pseudomonal ß-lactam -- Piperacillin/ Tazobactam 3 x 4,5 g iv 7 10 d -- Ceftriaxone 1 x 2,0 g iv 7 10 d -- Cefotaxime 3 x 2,0 g iv 7 10 d - plus Macrolide Alternative Fluoroquinolone - Levofloxacin 2 x 0,5 g iv 7 10 d - Moxifloaxin 1 x 0,4 g iv 7 10 d

37 Inpatient therapy in severe CAP with risk factors for P. aeruginosa A Compound Dosage (per d) Duration Anti-pseudomonal ß-lactam -- Piperacillin/ Tazobactam 3 x 4,5 g iv 7 10 d -- Cefepime 3 x 2,0 g iv 7 10 d -- Imipenem 3 x 1,0 g iv 7 10 d -- Meropenem 1 x 1,0 g iv 7-10 d - plus Macrolide or plus Fluoroquinolone - Levofloxacin 2 x 0,5 g iv 7 10 d - Ciprofloxacin 1 x 0,4 g iv 7 10 d

38 General recommendations for the treatment in hospital Initial parenteral therapy Exemption: flouroquinolones (1) Exemption: macrolides in combination (1) High dosage (4) Oral sequential therapy (1) Limited duration of therapy (2) 7-10 Tage Wasserfallen 2004; Dibar 2003; Vergis 2000

39 Summary Quality of management may be improved by evidence-based guidelines Crucial is a good mix of internal and external evidence Challenge: impementation of guideline Constant up-dating Individualise antibiotic treatment

40 Consensus Conference Invited Scientific Societies/Institutions Berufsverband der Allgemeinärzte Deutschlands Hausärzteverband (BDA) e.v. Berufsverband der Pneumologen e.v. (BDP) - Dachverband der Landesverbände der Pneumologen Deutschlands Berufsverband der Deutschen Internisten (BDI) e.v. Bundesministerium für Gesundheit und Soziale Sicherung (BMGS) Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM) e.v. Deutsche Gesellschaft für Hygiene und Mikrobiologie e.v. (DGHM) Deutsche Gesellschaft für Innere Medizin e.v. (DGIM) Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN) e.v. Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI) e.v. Medizinischer Dienst der Spitzenverbände (MDS) Patientenliga Atemwegserkrankungen e.v.