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A Survey From Major Guidelines . the treatment of CAP & bronchitis

A Survey From Major Guidelines ..in the treatment of CAP & bronchitis. Prepared by: Magdy El-Shafei Pharm B Group Product Manager M edical U nion P harmaceuticals. M.U.P. For the memory of a great Egyptian person in industry, Medical practice and Manhood.. Prof./ Zakareya Gad.

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A Survey From Major Guidelines . the treatment of CAP & bronchitis

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  1. A Survey From Major Guidelines..in the treatment of CAP & bronchitis Prepared by: Magdy El-Shafei Pharm B Group Product Manager Medical Union Pharmaceuticals M.U.P.

  2. For the memory of a great Egyptian person in industry, Medical practice and Manhood..Prof./ Zakareya Gad Honorarium

  3. Objective To discuss the recommendations outlined by major guidelines For Bronchitis and CAP Infectious Diseases Society of America American Thoracic Society The Canadian guidelines for the management of AECB, With a particular focus on what M.U.P. Offers for the best of our patients, Doctors and medical practice.

  4. In AECB(ABECB) Controversial role of antibiotics • FEV1 > 50% • Exacerbations =OR> 4 /Yr. • Heart diseases • Use of Oxygen • Antibiotics in the last 3 mo.

  5. How the antibiotics Are chosen for AECB Contribute -With M. Ctarrahlalis- to 30-50% of bronchitis 10-15% • Evidence-based practice • Best outcome for patients • Best use of resource • Least resistance • Least cost • Restricts idiosyncratic behaviour Staph. aureus Strept. Pneumonia Klebsiella Pneumonia Haemophylus influenzae >5 to 15% Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  6. In Pneumonia 70% of the cases 1% Co-morbidities, Elderly 31.8 % 61.0 % Strept. Pneumonia Staph. aureus 35.7 % Mortality Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Probably the most common cause of community-acquired pneumonia 14.7 % Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  7. Antibiotics differences G+ Ampicillin Amoxicillin Strept. Pneumonia Staph. aureus G- Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Atypical Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila Clinical treatment failure

  8. Antibiotics differences Macrolides azithromycin Clarithromycin (spiramycin) G+ Strept. Pneumonia Staph. aureus G- Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Atypical Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  9. Antibiotics differences 3rd generation cephalosporins G+ Strept. Pneumonia Staph. aureus G- As penicillin resistance rates increase the rates and degrees of cephalosporin resistance increase Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Atypical Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  10. Recent Studies done In Kasr El Aini Hospitals: 2009 – 2010 E.coli and Klebsiella producing cephalosporinase (ESBL) reached 75% in one study and 90% in another study* *Prof Dr. Maha Gaafar IC Dept. ElQuasr el Einy univ. hosp 2010

  11. Antibiotics differences G+ FQ Ciproxacin Strept. Pneumonia Staph. aureus G- Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Atypical Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  12. Antibiotics differences G+ FQ Moxifloxacin levofloxacin Strept. Pneumonia Staph. aureus G- Klebsiella Pneumonia Haemophylus influenzae P. aeruginosa Atypical Mycoplasma Pneumonia Chlamydia Pneumonia Legionella Pneumophila

  13. 2010 -11 Surfing across major guidelines In cases of acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP), recent guidelines suggest: using fluoroquinolone (moxifloxacin – levofloxacin) antibiotics as first-line therapy. This suggestion is based on level I evidence from several trials (clinical and microbial superiority of these agents). Fluoroquinolones (moxifloxacin – levofloxacin) shorten hospital stay, reduce recurrences, and lower costs. Resistance is still very low. M. Balter – CFP 2002 & 2010

  14. 2002 2011 Canadian guidelines recommendations for the treatment of AECB If symtoms persist >10 D  second- or third-generation cephalosporin second-generation macrolide Aminopenicllin second- or third-gen. cephalosporin 2nd gen. macrolideCiprofloxacin Moxifloxacin- levofloxacin penicillin + B-la ctamase inhibitor (Amox. – Clav) Or (AMPICILLIN/SULBACTAM) MoXacin LEVANIC UNICTAM + Ciprofloxacin Consider infusion

  15. Initial empiric therapy for suspected bacterial community-acquired pneumonia (CAP) in immunocompetent adults. LAST UPDATES: I D S A G U I D E L I N E S SPIREX Out patients MoXacin LEVANIC UNICTAM + Inpatients UNICTAM + MoXacin LEVANIC

  16. A study was designed to test whether cephalosporin resistance could be reversed by withdrawing these agents. The hospital-wide cephalosporin class restriction resulted in a 44% reduction in ceftazadine-resistant Klebsiella infection and colonization. COULD CEPHALOSPRINS resistance BE REVERSED?? UNICTAM 3 Gram Richard R. Yates Chest 1999

  17. COULD CEPHALOSPRINS resistance BE REVERSED?? Rahal; JAMA, October, 1999

  18. Managing AECB & CAPIn today`s guidelines CDC IDSA Mayo Clinic Respiratory quinolones 3rd generation (levofloxacin) 4th generation (Moxifloxacin) Alone or plus Amp./sulbactam Combination penicillins B- lactamase irreversible Inhibitors Like Ampicillin/sulbactam Amoxicillin/ clavlanic (in CAP:Plus a macrolide)

  19. Moxifloxacin structure activity relationship 8 O H3C • Higher gram-positive activity • Minimizes efflux (S. pneumoniae, S. aureus) OH O Mode of action that minimizes micro resistance F 4 5 O 3 6 2 H 7 N 1 N NH H A greater binding Affinity to the topoisomerase enzyme • Minimizes development of resistance • Enhances anaerobic activity Petersen et al 1996 Domagala, JM 1994

  20. Moxifloxacin Bactericidal in RECORD TIME 1000 000 CFU TO 1000 CFU Eradication in 3hrs. WIEDEMANN, Poster P0773, ECCMID Berlin 1999

  21. Modern 4th Generation F.Quinolone WithGreater antimicrobial power onG +ve bacteria Moxifloxacininhibits about 90%of strept. strains, while ciprofloxacin only inhibits 42%. International Journal of Antimicrobial Agents 20 (2002) 196/200

  22. MORDERN: 4th Generation F.Quinolone 5times higher concentrations over ciprofloxacin In Alveolar Macrophages Data on File *Mean ± SD measured 3H after dosing with 400 mg Andrews, et al. JAC 40:573-577, 1997 **Measured 2 and 4H after dosing with 500 mg ciprofloxacin

  23. Tissue Penetration MoxifloxacinHigh Respiratory Tissue Penetration 100 100 (mg/l) MIC90 10 1 0.12 S.pneumoniae, M.Catarrhalis 0.1 0.06 H.influenzae 0.01 Bronchial Mucosa Epithelial Lining Fluid(ELF) Alveolar Macrophage Respiratory tissue concentration after one single p.o dose Andrews J et al.38th ICAAC, 1998;San Diego, A29

  24. moxifloxacinClinical Success

  25. CMAJ. 2008 March comparisons of effectiveness and safety between fluoroquinolones and β-lactam antibiotics. indicates a statistically significant difference favours fluoroquinolone therapy;.

  26. In AECB A single-arm analysis, comparing the efficacy of moxifloxacin with ciprofloxacin in patients with acute exacerbation of chronic bronchitis (AECB) Adapted from ref. 1 1.Mittmann N, Jivarj F, Wong A, Yoon A. Oral fluoroquinolones in the treatment of pneumonia, bronchitis and sinusitis. Can J Infect Dis. 2002; 13 (5): 293-300.

  27. AECB ( Cont’d) A randomized, non-blinded, multinational, multicentre study comparing the efficacy of moxifloxacin with amoxicillin/clavulanate in 512 evaluable patients with clear signs of AECB. Adapted from ref. 2 2.Schaberg T, Ballin I, Huchon G, et al. A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis. J Int Med Res 2001; 29 (4): 314-28.

  28. Fast Eradication of Respiratory pathogens. • Quick relief of symptoms. • Rapid and Complete clinical cure. • Rare bacterial resistance. • Minimal Risk of Drug/food Interaction. • No Dose adjustment in elderly , renal or hepatic patients.

  29. Empirical Antimicrobial Therapy for Community-Acquired Pneumonia In Immunocompetent Adults ‡Levofloxacin, gatifloxacin, moxifloxacin.§Critically ill patients in areas with significant rates of high-level pneumococcal resistance and a suggestive sputum Gram stain should receive vancomycin or a newer quinolone pending microbiologic diagnosis.¶ampicillin-sulbactam orPiperacillin-tazobactam. ¶Cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin-clavulanate, or parenteral ceftriaxone followed by oral cefpodoxime. **Cefotaxime, ceftriaxone, ampicillin-sulbactam, or high-dose ampicillin

  30. What MUP offers Be sure to cure in the time ofBIG CHALLENGERTIs • Quality • Scientific credibility • Price • Best outcome for patients • Best use of resource • Least resistance • Least cost • Restricts idiosyncratic

  31. UNICTAM What MUP offers • Quality • Scientific credibility • Price Ampicillin/sulbactam Saving Cephalosporins abuse • Best outcome for patients • Best use of resources • Least resistance • Least cost • Restricts idiosyncratic Prof/ Maha Gaafar IC Dept. ElQuasr el Einy univ. hosp 2010

  32. From Cleveland to Baltimore to Cairo Few years ago with Prof. Dr Awad Tag ElDin The Egyptian Society of Chest & Tuberculosis For what the martyrs died for better, free & dignity Egypt

  33. FEV1 > 50% • Exacerbations =OR> 4 /Yr. • Heart diseases • Use of Oxygen • Antibiotics in the last 3 mo. One Or More None • Did not • improve • Group 1 • 2nd G Macrolide • 2nd or 3rd G cephalosporins • TMO-SMX • Doxycyclene • Group II • FQ • B-lactam/Blactamase • Ampicillin/sulbactam • Group III • Anbulatory patient • Hospitalized patient: • Consider Ps. Aeroginosae • Ciprofloxacin infusion worsen Improved Improved • FQ • Moxacin - Levanic • Did not • improve Can Resp J 2003

  34. Empiric Treatment – Outpatient: No confounding factors: macrolide (azithromycin 500mg x 1 day then 250mg Qday or clarithromycin 500mg po Q12hrs or clarithro-ER 1000mg Qday) or doxycycline 100mg Q12hrs CAP:IDSA-ATS Treatment Guidelines

  35. CAP:IDSA-ATS Treatment Guidelines • Empiric Treatment – Outpatient: • Confounding factors present: respiratory quinolone(levofloxacin 750mg Qday, moxifloxacin 400mg Qday) or beta-lactam (amoxicillin 1g Q8hrs, amox-clav-ER 2gm Q12hrs, cefpodoxime 200mg Q12hrs, cefdinir 300mg Q12hrs, etc)+ macrolide or beta-lactam + doxycycline

  36. Empiric Treatment – Hospitalized, non-ICU: Beta-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam, or ertapenem) + macrolide or doxycycline or Respiratory quinolone alone (levofloxacin, moxifloxacin, gemifloxacin) CAP:IDSA-ATS Treatment Guidelines

  37. Empiric Treatment – Hospitalized, ICU: Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) + macrolide or respiratory quinolone PCN-allergic = resp quinolone + aztreonam CAP:IDSA-ATS Treatment Guidelines

  38. Fluoroquinolones for Respiratory Infections Comparison of Recent Guidelines for Empiric Initial Therapy of CAP* Williams J. Jr. • * ± = with or without; PCN = penicillin.

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