1. Management of Community Acquired Pneumonia ATS/IDSA Guidelines 2006 Mazen Kherallah, MD, FCCP Consultant, Infectious Disease and Critical Care Medicine King Faisal Specialist Hospital & Research Center www.icumedicus.com

2. CAP Guidelines  BTS, Canadian, ATS (1993)  IDSA, ERS (1998)  DRSPTWG (2000)  IDSA (2000), Canadian (2000), JRS (2000)  ATS (2001), BTS (2001)  IDSA (2003) Mandell et al; CID (2003)  ATS/IDSA (2006)

3. Site of Care

4.  Significant impact on:  Extent of laboratory evaluation  Antimicrobial therapy  Advantage of outpatient therapy:  Cost  Patient preference  Faster convalescence and avoidance of nosocomial complications  Decisions:  Hospital vs outpatients  Intensive care vs general wards

5. Pneumonia Severity Index ClassPointsMortality*Site of Care I<510.1%OutPatient II51-700.6%OutPatient III71-902.8%In or OutPatient IV91-1309.5%Inpatient V>13026.7%Inpatient

6. CURB-65 Score: 1 C onfusion (new disorientation in person, time or place) 1 Elevation of blood U rea, or blood urea nitrogen (BUN) level above 7 mmol/L (urea) or 20 mg% (BUN) 1 R espiratory rate >= 30 breaths/min 1 Low B lood pressure, < 90 mm Hg systolic OR =<60 mm Hg diastolic 1 Age >= 65 years Score% MortalitySite of Care 00.7Outpt 11-3.2Outpt 22-9Hospital 317ICU 441.5ICU 557ICU Lim et al. Thorax 2003;58:377

7. Clinical Indications for more Extensive Diagnostic Testing. Minor criteriaMajor criteria Respiratory rate 30 breaths/minInvasive mechanical ventilation PaO2/FiO2 ratio 250Septic shock with the need for vasopressors Multi-lobar infiltrates Confusion/disorientation Uremia (BUN level, 20 mg/dL) Leukopenia (WBC count, >4000 cells/mm 3 ) Thrombocytopenia (platelet count, !100,000 cells/mm 3 ) Hypothermia (core temperature, <36 ° C) Hypotension requiring aggressive fluid resuscitation Recommended ICU admission if either major or at least three minor criteria

8. Diagnostic Testing

9. Clinical Diagnosis  Cough, fever, sputum production, and pleuritic chest pain)  Supported by imaging of the lung, usually by chest radiography.

10. Clinical Indications for more Extensive Diagnostic Testing.

11. PathogenRapid TestStandard TestOther S. PneumoniaeGram stain Urine antigen Blood and respiratory cultures H. InfluenzaeGram stainBlood culture M. PneumoniaePCR*Ab-ELISA 1 Culture C. PneumoniaePCR*Ab-MIF 2 Culture L. pneumophiliaUrine antigen a PCR* DFA 3 Respiratory culture Ab-IFA Culture (media) Not FDA approved a sensitivity 60-80%; specificity >90% 1 IgM (1-50 weeks),, 2 Primary infection-IgM (4-6 weeks) IgG (often >6 weeks); 3 False positives with sputum. Recommended Diagnostic Tests for Etiology

12. Urinary Antigen for S. pneumoniae (UrSp)  Immunochromatographic test  Sensitivity 50-80% (80-90% for bacteremia)  Specificity ~ 90%  In prospective study, of 269 patients with CAP and no pathogen identified, UrSp detected in 69 (27.5%) [Gutierrez et al. CID, 2003]  False positive in children (oropharyngeal colonization); Streptococcus spp. Bacteremia  Recommended as ancillary test (not as substitute for culture) Mandell L et al. Clin Inf Dis, 2003

13. Blood Cultures  Blood cultures for all inpatients probably has some benefits, but limited and associated with increased cost and inappropriate antibiotic  False positive > true pathogen in less ill patients  Strategy which targets higher risk patients seems reasonable  Limit number of blood cultures by  Targeting the patients at highest risk of bacteremia (Mastesky, Am J Resp Crit Care Med, 2004)  Targeting patients with highest risk of mortality (Fine, NEJM 1997)  New CMS/JCAHO  All patients with severe CAP (ICU)  Optional for general ward patients (but not discouraged)  If drawn in ER, before administration of antibiotics

14. Antibiotic Treatment

15. Most common etiologies of community-acquired pneumonia Ambulatory PatientsHospitalized (Non-ICU) 2 Severe (ICU) 2 S. pneumoniae M. pneumoniae Legionella spp. H. InfluenzaeC. pneumoniaeH. Influenzae C. pneumoniaeH. InfluenzaeGram-negative bacilli Respiratory viruses 3 Legionella spp.S. aureus Aspiration Respiratory viruses 3 1 Based on collective data from recent studies 2 Excluding Pneumocystis spp. 3 Influenza A and B, adenovirus, respiratory syncytial virus, and parainfluenza. Adapted from File T. Lancet 2003

17. Risk factors for infection with b-lactam–resistant S. pneumoniae  Age 65 years  Previous b-lactam therapy within the previous 3 months  Alcoholism  Medical comorbidities  Immunosuppressive illness or therapy  Exposure to a child in a day care center

18. Treatment of Respiratory Tract Infections  Empiric  Historically ß-lactams have been the agent of choice  Publication of treatment guidelines for CAP in the 1990s recommend macrolides for first-line use*  Increase in macrolide use worldwide  Also an increase in macrolide resistance  Macrolide resistance is now more common in some areas than ß-lactam resistance *Niederman MS et al. Am Rev Resp Dis 1993;148:1418-1426

22. Antibiotic Choice: Outpatient PSI <91 (Class I, II, III) or CURB-65 score 0-1 Previously healthy and no risk factors for drug-resistant S. pneumoniae (DRSP) infection: A. A macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence) B. Doxycycline (weak recommendation; level III evidence) Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; Use of antimicrobials within the previous 3 months: A. A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) (strong recommendation; level I evidence) B. A b-lactam plus a macrolide (strong recommendation; level I evidence): High dose amoxicillin, amoxicillin-clavulanate ceftriaxone, cefpodoxime, and cefuroxime. Doxycycline [level II evidence] is an alternative to the macrolide. In regions with a high rate (>25%) of infection with high-level (MIC >16 mg/mL) macrolide-resistant S. pneumoniae, Consider the use of alternative agents listed above for any patient, including those without comorbidities. (Moderate recommendation; level III evidence.)

23. Antibiotic Choice: Inpatient PSI >90 (Class IV) or CURB-65 score 2-5 Inpatient: Non-ICU Treatment Respiratory fluoroquinolone (strong recommendation; level I evidence) B-lactam plus a macrolide (strong recommendation; level I evidence) (cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients) Inpatient, ICU Treatment B-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (level II evidence) or a fluoroquinolone (level I evidence) (strong recommendation) For Pseudomonas infection, use an antipneumococcal, antipseudomonal b lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin or the above b-lactam plus an aminoglycoside and azithromycin or the above b-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (Moderate recommendation; level III evidence.) For community-acquired methicillin resistant Staphylococcus aureus infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence.)

24. Others Penicillin I or R 47% PSI >90 (Class I, II, III) or CURB-65 score 2-5 S. Pneumonia Viral Previously well, no prior ATB Macrolide, ( azithromycin, clarithromycin, or erythromycin) Doxycycline Medical morbidity or use of antimicrobials within the previous 3 months Respiratory fluroquinolone* (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) High dose β-lactam + macrolide Risk of aspiration Am-CL; Clindamycin General Word ICU No risk for pseudomonasRisk for psudomonas: brinchiectasis, recent ATB, prior ICU hospitalization Respiratory fluroquinolones β-lactam* + macrolide β-lactam* + macrolide or respiratory quinolone Antipseudomonas β-lactam** + ciprofloxacin PSI <91 (Class I, II, III) or CURB-65 score 0-1 *Amox-CL, Cefotaxime, Ceftriaxone or Ertapenem **Pipercillin, imipenem, meropenem, cefepime ***Moxifloxacin, gemifloxacin, levofloxacin Atypicals et al IDSA:2006 H. Flu

25. Time to First Antibiotic Dose

26. Timing of Antibiotic Administration  IDSA 2000: within 8 hours (Meehan et al. JAMA, 1997)  IDSA 2003: “Goal” within 4 hours (ouck et al: Arch Intern Med 2004; 164:637-44)  A problem of internal consistency is also present, because, in both studies, patients who received antibiotics in the first 2 h after presentation actually did worse than those who received antibiotics 2–4 h after presentation.  The first antibiotic dose should be administered while still in the ED. (Moderate recommendation; level III evidence.)

27. Switch from Intravenous to Oral Therapy

28.  Patients should be switched from intravenous to oral therapy when they are:  Hemodynamically stable  Improving clinically  Are able to ingest medications  Have a normally functioning gastrointestinal tract. (Strong recommendation; level II evidence.)  Patients should be discharged as soon as they are:  clinically stable  Have no other active medical problems  Have a safe environment for continued care.  Inpatientobservation while receiving oral therapy is not necessary. (Moderate recommendation; level II evidence.)

29. Criteria for clinical stability.  Temperature 37.8C  Heart rate 100 beats/min  Respiratory rate 24 breaths/min  Systolic blood pressure 90 mm Hg  Arterial oxygen saturation 90% or pO2 60 mm Hg on room air  Ability to maintain oral intake  Normal mental status

30. Criteria for clinical stability. Halm EA, et al.. Arch Intern Med 2002; 162:1278–84.

31. Duration of Therapy

34. Community-Acquired MRSA

35. Case of Severe CAP  30 year old female presents to ER at 04:00 with acute fever, dough, and dyspnea  Recent ‘viral syndrome’  Severe hypoxemia  Requires immediate intubation  Treated with 3 rd gen ceph pluse fluroquinolone

36. Case of Severe CAP  Gram stain of ET aspirate reveals GPC in clusters  Vancomycin was added  Patient has multi- organ dysfunction expires at 16:00  CA-MRSA isolated

37. Case of Severe CAP  Gram stain of ET aspirate reveals GPC in clusters  Vancomycin was added

38. Case of Severe CAP  Patient has multi- organ dysfunction expires at 16:00  CA-MRSA isolated

39. CA-MRSA Pneumonia  Newly recognized pathogen: community- onset MRSA  Genotypically and phenotypically distinct HA-MRSA  Often associated with severe disease  Panton Valentine Leukocidin (PVL)  Associated with preceding influenza  Pending new data; vancomycin or linezolid recommended for initial therapy for severe disease Framcis et al. Clin Inf Dis. 2004;40:100-7, Wago and Eiland Clin Infect Dis. 2005;40:1376

40. Response to Therapy

45. Thank You