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Evidence-Based Decisions and FA (Clinical) Q’s: Community Acquired Pneumonia

Evidence-Based Decisions and FA (Clinical) Q’s: Community Acquired Pneumonia. John H. Burton, MD Dept. Emergency Medicine Albany Medical Center. Lecturing on CAP. Research Grants: Binax , Medtronic, Scios EMF, NIH . Lecture Sponsorship: 20+ Hospitals, Roche, Bristol-Myers Squibb,

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Evidence-Based Decisions and FA (Clinical) Q’s: Community Acquired Pneumonia

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  1. Evidence-Based Decisions and FA (Clinical) Q’s:Community Acquired Pneumonia John H. Burton, MD Dept. Emergency Medicine Albany Medical Center

  2. Lecturing on CAP Research Grants: Binax, Medtronic, Scios EMF, NIH Lecture Sponsorship: 20+ Hospitals, Roche, Bristol-Myers Squibb, Pfizer, Bayer, Scios, Aventis

  3. Lecturing on CAP How much money do you Receive to do a lecture via pharma? Initially: 500.00/lecture 5 years in: Local: 750.00 Travel: 1000.00 Most: 2000.00/ 45 min

  4. Bronchitis vs CAP?

  5. Bronchitis:1. URI symptoms: cough, fever, congestion, +/- sputum production (color change…) 2. Vast majority are viral..3. Don’t treat with antibiotics4. Consider beta-agonists (2 studies, weak data) CAP: Class I:1. URI symptoms: cough, fever, congestion, +/- sputum production, +CXR (Class I exception)2. Treat with antibiotics

  6. How should the disposition be determined in patients with community acquired pneumonia?

  7. A Prediction Rule to Identify Low-Risk Patients with CAPNEJM 1997; 336:243-250. • Develop a prediction rule for prognosis to identify pts at low risk of dying within 30 days. • Analysis of data on 14,199 adults in a with CAP treated as inpatients. • Prediction rule then validated on database of 38,000 CAP pts.

  8. Pred Rule for Low Mortality…Step 1 > 50 yoa Comorbid? Neoplasm CHF Cerebral Renal Hepatic EXAM: Alt LOC HR > 125 RR > 30 SBP < 90 T < 35 > 40 NO NO NO Assign Class I YES YES YES Assign Class II-V by Lab and CXR

  9. Pred Rule for Low Mortality • Class I /II< 1% mortality Class III - 2.8 Class IV - 9% Class V - 27%

  10. Pred Rule for Low Mortality…Next Step... Neoplasm +30 Hepatic +20 CHF +10 Cerebral +10 Renal +10 PH < 7.35 + 30 BUN > 30 +20 Na < 130 +20 Glu >250 +10 Hct < 30 +10 PO2 < 60 +10 Class: I II < 70 pts III 71-90 IV 91-130 V > 130 Alt LOC +20 RR > 30 +20 SBP < 90 +20 T<35 >40 +15 HR > 125 +10 Pleural Eff +10 Male Age Female Age -10 Nursing Home +10

  11. What Should I Prescribe for Outpatients with CAP?

  12. Community-Acquired Pneumonia Bacterial Causes Hosp Form 1994; 29: 122-136

  13. Outpatients with CAP? *Comrbd = copd, ca, chf, dm, renal

  14. Outpatients with CAP? *Comrbd = abx 3 mos, copd, ca, chf, dm, renal, etoh, asplenia

  15. Should I Cover Atypical Pathogens in Hospitalized Patients?

  16. Assoc. Between Initial Antimicrobial Tx & Med Outcomes for Hospitalized Elderly Pts with PneumoniaArch Intern Med 99;159:2562-2572 • 12,945 eligible pts: 9751 from community 3194 from long-term facility • Mean age 79 years

  17. 95% Conf I

  18. Atypical Pathogens in Hospitalized Patients? Yes NoIDSA 2000 Sanford 2000 ATS 2001CIDS/CTS 2000IDSA 2003

  19. Atypical Pathogens in Hospitalized Patients? Yes NoIDSA/ATS 20071. Resp Fqln2. Beta+Macrld(both Levl 1)

  20. What’s the Deal with Macrolide Resistance?

  21. Macrolide-Resistant S. pneumoniae: ** Current estimates: 20-30% depending on region or country. Clin Infect Dis. 1992;15:95-98 JAMA 94; 271, 1831-1835.

  22. Pneumococcal macrolide resistance - myth or realityJour Antimicrob Chem 1999; 44:1-6 “Despite the in-vitro resistance trends ….there is a paucity of data indicating resistance trends are translating into in vivo clinical failures..it appears the opposite is true.” Significance of Serum vs Tissue Levels of Abx in Treatment of PRSP & CAPChest 1999; 116:535-538 “Clinical results in pneumonia may depend more on tissue penetration and accumulation in the infected lung than on serum levels.” No correlation of increasing in vitro resistance has been made with mortality outcomes.

  23. Practice Guidelines for the Management of CAP: IDSA 2000 Clin Inf Dis 2000; 31:347-82 “Cases of macrolide failure have been described anecdotally but have been infrequent so far.” Canadian Guidelines: CIDS/CTS Clin Inf Dis 2000; 31:383-421 “Very few cases have been reported in which ..macrolide resistance has led to clinical failure or breakthrough bacteremia.”

  24. Update of Practice Guidelines for Management of CAP in Immunocompetent AdultsClin Inf Disease 2003;37:1405-33 “S Pneumo resistance in vitro may be deceptive, because the M phenotype may not be clinically relevant, and alveolar lining fluid or intracellular levels may be more important than serum levels used to determine in vitro activity.”

  25. Does the fluoroquinolone choice make a difference?

  26. Generations of Fluoroquinolones • 1st: Nalidixic Acid • 2nd: Cipro/Ofloxacin • 3rd: Levofloxacin • 4th: Gatifloxacin, Moxiflox (improved Gram Pos and Anaerobe)

  27. Adverse Events: Quinolones CNS seizures & dizziness (sparfloxacin, trovafloxacin ofloxacin) Prolonged QTc interval (grepafloxacin, gatifloxacin, levofloxacin, sparfloxacin, moxifloxacin) Taste perversion (grepafloxacin) Phototoxicity (sparfloxacin, lomefloxacin, clinafloxacin) GI nausea/vomiting (all quinolones) Arthritis/Tendonitis (all quinolones) Liver toxicity (trovafloxacin) Adapted from Fish. Clin Pharmacokinet. 1997;32:101-119. Haria. Drugs. 1997;54:435-446. Goa. Drugs. 1997;53:700-725. Wagstaff. Drugs. 1997;53:817-824. Avelox (moxifloxacin) package insert.

  28. Current Indications and Uses for the Fluoroquinolones Gatifloxacin Levofloxacin Moxifloxacin AECB + + + 5 day + - + CAP + + + Acute Sinusitis + + + UTI + + - Comp. UTI/Pyelo + + - Uncomp. Gonorr. + --

  29. What’s the Deal with Fluoroquinolone Resistance?

  30. Fluoroquinolone ResistanceTHE BAD NEWS • Resistances to Levoflox have been reported recently. • Increasing number of centers are reserving fluoroquinolones for the sickest patients and oldest: Umass, Brigham, etc...

  31. What’s the Deal with Fluoroquinolone Resistance?(CDC:Drug-Resistant Strep Pneumo Working Group) Fluoroquinolones Limited to: -Adults who have failed Macrolide, BLactam-Macrolide combo, or Doxy -Allergy to alternative agents -Documented PRSP infection Arch Int Med 2000;160:1399-1408.

  32. What’s the Deal with Fluoroquinolone Resistance?(JB’s Rules) You may choose to reserve Fluoroquinolone use: -Increased Age (>70) -Highest Severity -Risk of PRSP (Nursing home patients) -Increased Risk: Cardiopulmonary Disease

  33. Give the Best Drugs to the Oldest (and Sickest) Folks... IDSA 2003 For Nursing Home Pts 1. Resp Flouroquinln 2. Amx/Clv + Az/Clrth

  34. What are cost-effective treatment strategies?

  35. Prestigious Burton Survey2004 10d 14d Zmax 47 (5d) Biaxin 82 114 Doxy 11 13 Lvquin 92 128 Gatiflox 85 118 Moxiflox 91 126 Augmtn 113 155 Walmart Pharmacy: Falmouth, ME Ver Imp Med Jour, 2004

  36. Why Can’t I use Doxycycline on everyone? IDSA 2003:“Very limited recent published clinical data on CAP, and few clinicians use it.”

  37. Why not use Erythromycin on Everyone? IDSA 2003:“Erythromycin is poorly tolerated and is less effective against H Influenzae.”

  38. How long a course of therapy? 1. Until Afebrile for 72 hours.2. Numerous trials: 7-14 days.3. No controlled, outcome trials. 4. It’s a wash - 10 days.

  39. Are there any new drugs in the pipeline or pharmacy? • 12-Membered Ring • Methymycin • 16-Membered Ring • Spiramycin 14-Membered Ring • 15-Membered Ring • Azithromycin • Natural Erythromycin • A, B, C, etc • Semisynthetic • Clarithromycin • Dirithromycin • Flurithromycin • Roxithromycin Ketolides (telithromycin) Bryskier A. Macrolides: Chemistry, Pharmacology and Clinical Uses. Oxford, England: Blackwell Scientific Publications; 1993.

  40. What’s the deal with all this 4 hour business for time to antibiotics?

  41. JCAHO CAP Indicators Quality of Care, Process, Outcomes in Elderly with PneumoniaJAMA 1997; 278:2080-2084 • Smoking cessation program • Pneumovax program and documentation • Time to Antibiotics (less than 8h) - less than 4h • Blood Cultures for admitted patients

  42. Odds of Survival at 30days vs Time to Antibiotic JAMA 1997; 278:2080-2084

  43. What’s the deal with cultures? Don’t Get Em:1. Positive approx 8%2. When Positive, no change in RX3. Cost: Patient discomfort, false positive, contaminants, etc..Get Em:1. JCAHO interest2. Association with decreased mortality.3. Microbiologic/Resistance monitoring

  44. Clinical Utility of Blood Cultures in Adult Pts with Comm-Acqd Pneumonia Chest 1995; 108:932-936 Culture Result 517 Community Acquired Pnemonia Pts

  45. Clinical Utility of Blood Cultures • Blood Culture (+) 34 patients: Strep Pneumo - 29 H Flu - 3 Strep Pyogenes- 1 E Coli - 1

  46. Utility of Blood Cultures in Pediatric ED Pts with Pneumonia Ann Emer Med 1996; 27:721-725 11 patients (+) cultures 10 - S Pneumo 1 - H Parainfluenzae 409 pts with cultures

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