1. Community-Acquired Pneumonia

2. Objectives  Describe the common pathogenesis and pathogens of pneumonia  Discuss diagnosis and initial management of community acquired pneumonia (CAP)  Understand features of the Pneumonia PORT Severity Index  Discuss the IDSA/ATS guidelines and recommendations for final antibiotic choice  Understand issues in basic management for pneumonia in children, nursing home patients, and immunocompromised patients.

3. Epidemiology  Unclear! Few population-based statistics on the condition alone  CDC combines PNA with influenza for morbidity & mortality data PNA & influenza = 7th leading causes of death in the US (2001) PNA & influenza = 7th leading causes of death in the US (2001) Age-adjusted death rate = 21.8 per 100,000 Age-adjusted death rate = 21.8 per 100,000 Mortality rate: 1-5% out-Pt, 12% In-Pt, 40% ICU Mortality rate: 1-5% out-Pt, 12% In-Pt, 40% ICU Death rates increase with comorbidity and age Death rates increase with comorbidity and age Affects race and sex equally Affects race and sex equally

4. Community Acquired Pneumonia  Infection of the lung parenchyma in a person who is not hospitalized or living in a long-term care facility for ≥ 2 weeks  5.6 million cases annually in the U.S.  Estimated total annual cost of health care = $8.4 billion  Most common pathogen = S. pneumo (60- 70% of CAP cases)

5. “Nosocomial” Pneumonia  Hospital-acquired pneumonia (HAP) Occurs 48 hours or more after admission, which was not incubating at the time of admission Occurs 48 hours or more after admission, which was not incubating at the time of admission  Ventilator-associated pneumonia (VAP) Arises more than 48-72 hours after endotracheal intubation Arises more than 48-72 hours after endotracheal intubation

6. “Nosocomial” Pneumonia  Healthcare-associated pneumonia (HCAP) Patients who were hospitalized in an acute care hospital for two or more days within 90 days of the infection; resided in a nursing home or LTC facility; received recent IV abx, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic Patients who were hospitalized in an acute care hospital for two or more days within 90 days of the infection; resided in a nursing home or LTC facility; received recent IV abx, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic  Guidelines for the Management of Adults with HAP, VAP, and HCAP. American Thoracic Society, 2005

7. Pathogenesis  Inhalation, aspiration and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs  Primary inhalation: when organisms bypass normal respiratory defense mechanisms or when the Pt inhales aerobic GN organisms that colonize the upper respiratory tract or respiratory support equipment

8. Pathogenesis  Aspiration: occurs when the Pt aspirates colonized upper respiratory tract secretions Stomach: reservoir of GNR that can ascend, colonizing the respiratory tract. Stomach: reservoir of GNR that can ascend, colonizing the respiratory tract.  Hematogenous: originate from a distant source and reach the lungs via the blood stream.

9. Pathogens  CAP usually caused by a single organism  Even with extensive diagnostic testing, most investigators cannot identify a specific etiology for CAP in ≥ 50% of patients.  In those identified, S. pneumo is causative pathogen 60-70% of the time

10. Streptococcus pneumonia  Most common cause of CAP  Gram positive diplococci  “Typical” symptoms (e.g. malaise, shaking chills, fever, rusty sputum, pleuritic hest pain, cough)  Lobar infiltrate on CXR  Suppressed host  25% bacteremic

11. Atypical Pneumonia  #2 cause (especially in younger population)  Commonly associated with milder Sx’s: subacute onset, non-productive cough, no focal infiltrate on CXR  Mycoplasma: younger Pts, extra-pulm Sx’s (anemia, rashes), headache, sore throat  Chlamydia: year round, URI Sx, sore throat  Legionella: higher mortality rate, water-borne outbreaks, hyponatremia, diarrhea Pneumonia

12. Viral Pneumonia  More common cause in children RSV, influenza, parainfluenza RSV, influenza, parainfluenza  Influenza most important viral cause in adults, especially during winter months  Post-influenza pneumonia (secondary bacterial infection) S. pneumo, Staph aureus S. pneumo, Staph aureus

13. Other bacteria  Anaerobes Aspiration-prone Pt, putrid sputum, dental disease Aspiration-prone Pt, putrid sputum, dental disease  Gram negative Klebsiella - alcoholics Klebsiella - alcoholics Branhamella catarrhalis - sinus disease, otitis, COPD Branhamella catarrhalis - sinus disease, otitis, COPD H. influenza H. influenza  Staphylococcus aureus IVDU, skin disease, foreign bodies (catheters, prosthetic joints) prior viral pneumonia IVDU, skin disease, foreign bodies (catheters, prosthetic joints) prior viral pneumonia

14. Diagnosis and Management

15. Guidelines  American Thoracic Society Guidelines for the Management of Adults with CA (2001) Guidelines for the Management of Adults with CA (2001)  Infectious Diseases Society of America Update of Practice Guidelines for the Management of CAP in Immunocompetent adults (2003) Update of Practice Guidelines for the Management of CAP in Immunocompetent adults (2003)  ATS and IDSA joint effort IDSA/ATS Consensus Guidelines on the Management of CAP in Adults (March 2007) IDSA/ATS Consensus Guidelines on the Management of CAP in Adults (March 2007)

16. Guidelines  2001 ATS & 2003 IDSA Guideline Update  Expert panels  Evidence-based recommendations  Recommend patient stratification to identify likely pathogens and suggested empiric abx Site of care Site of care Presence of cardiopulmonary disease Presence of cardiopulmonary disease Presence of “modifying factors” Presence of “modifying factors”

17. Clinical Diagnosis  Suggestive signs and symptoms  CXR or other imaging technique  Microbiologic testing

18. Signs and Symptoms  Fever or hypothermia  Cough with or without sputum, hemoptysis  Pleuritic chest pain  Myalgia, malaise, fatigue  GI symptoms  Dyspnea  Rales, rhonchi, wheezing  Egophony, bronchial breath sounds  Dullness to percussion  Atypical Sx’s in older patients

19. Clinical Diagnosis: CXR  Demonstrable infiltrate by CXR or other imaging technique Establish Dx and presence of complications (pleural effusion, multilobar disease) Establish Dx and presence of complications (pleural effusion, multilobar disease) May not be possible in some outpatient settings May not be possible in some outpatient settings CXR: classically thought of as the gold standard CXR: classically thought of as the gold standard

20. Infiltrate Patterns Pattern Possible Diagnosis Lobar S. pneumo, Kleb, H. flu, GN Patchy Atypicals, viral, Legionella Interstitial Viral, PCP, Legionella Cavitary Anaerobes, Kleb, TB, S. aureus, fungi Large effusion Staph, anaerobes, Kleb

21. Clinical Diagnosis: Recommended testing  Outpatient: CXR, sputum Cx and Gram stain not required  Inpatient: CXR, Pox or ABG, chemistry, CBC, two sets of blood Cx’s If suspect drug-resistant pathogen or organism not covered by usual empiric abx, obtain sputum Cx and Gram stain. If suspect drug-resistant pathogen or organism not covered by usual empiric abx, obtain sputum Cx and Gram stain. Severe CAP: Legionella urinary antigen, consider bronchoscopy to identify pathogen Severe CAP: Legionella urinary antigen, consider bronchoscopy to identify pathogen

22. Clinical Diagnosis  Assess overall clinical picture  PORT Pneumonia Severity Index (PSI) Aids in assessment of mortality risk and disposition Aids in assessment of mortality risk and disposition Age, gender, NH, co-morbidities, physical exam lab/radiographic findings Age, gender, NH, co-morbidities, physical exam lab/radiographic findings

23. IDSA: Outpt Management in Previously Healthy Pt  Organisms: S. pneumo, Mycoplasma, viral, Chlamydia pneumo, H. flu  Recommended abx: Advanced generation macrolide (azithro or clarithro) or doxycycline Advanced generation macrolide (azithro or clarithro) or doxycycline  If abx within past 3 months: Respiratory quinolone (moxi-, levo-, gemi-), OR Respiratory quinolone (moxi-, levo-, gemi-), OR Advanced macrolide + amoxicillin, OR Advanced macrolide + amoxicillin, OR Advanced macrolide + amoxicillin-clavulanate Advanced macrolide + amoxicillin-clavulanate

24. IDSA: Outpt Management in Pt with comorbidities  Comorbidities: cardiopulmonary dz or immunocompromised state  Organisms: S. pneumo, viral, H. flu, aerobic GN rods, S. aureus  Recommended Abx: Respiratory quinolone, OR advanced macrolide Respiratory quinolone, OR advanced macrolide  Recent Abx: Respiratory quinolone OR Respiratory quinolone OR Advanced macrolide + beta-lactam Advanced macrolide + beta-lactam

25. IDSA: Inpt Management- Medical Ward  Organisms: all of the above plus polymicrobial infections (+/- anaerobes), Legionella  Recommended Parenteral Abx: Respiratory fluoroquinolone, OR Respiratory fluoroquinolone, OR Advanced macrolide plus a beta-lactam Advanced macrolide plus a beta-lactam  Recent Abx: As above. Regimen selected will depend on nature of recent antibiotic therapy. As above. Regimen selected will depend on nature of recent antibiotic therapy.

26. IDSA: Inpt Management- Severe/ICU  One of two major criteria: Mechanical ventilation Mechanical ventilation Septic shock, OR Septic shock, OR  Two of three minor criteria: SBP≤90mmHg, SBP≤90mmHg, Multilobar disease Multilobar disease PaO2/FIO2 ratio < 250 PaO2/FIO2 ratio < 250  Organisms: S. pneumo, Legionella, GN, Mycoplasma, viral, ?Pseudomonas

27. IDSA: Inpt Management: Severe/ICU  No risk for Pseudomonas IV beta-lactam plus either IV beta-lactam plus either IV macrolide, OR IV fluoroquinoloneIV macrolide, OR IV fluoroquinolone  Risk for Pseudomonas Double therapy: selected IV antipseudomonal beta- lactam (cefepine, imipenem, meropenem, piperacillin/tazobactam), plus Double therapy: selected IV antipseudomonal beta- lactam (cefepine, imipenem, meropenem, piperacillin/tazobactam), plus IV antipseudomonal quinoloneIV antipseudomonal quinolone-OR- Triple therapy: selected IV antipseudomonal beta- lactam plus Triple therapy: selected IV antipseudomonal beta- lactam plus IV aminoglycoside plus either IV macrolide, OR IV antipseudomonal quinolone

28. Switch to Oral Therapy  Four criteria: Improvement in cough and dyspnea Improvement in cough and dyspnea Afebrile on two occasions 8 h apart Afebrile on two occasions 8 h apart WBC decreasing WBC decreasing Functioning GI tract with adequate oral intake Functioning GI tract with adequate oral intake  If overall clinical picture is otherwise favorable, can can switch to oral therapy while still febrile.

29. Management of Poor Responders  Consider non-infectious illnesses  Consider less common pathogens  Consider serologic testing  Broaden antibiotic therapy  Consider bronchoscopy

30. Prevention  Smoking cessation  Vaccination per ACIP recommendations Influenza Influenza Inactivated vaccine for people >50 yo, those at risk for influenza compolications, household contacts of high-risk persons and healthcare workersInactivated vaccine for people >50 yo, those at risk for influenza compolications, household contacts of high-risk persons and healthcare workers Intranasal live, attenuated vaccine: 5-49yo without chronic underlying dzIntranasal live, attenuated vaccine: 5-49yo without chronic underlying dz Pneumococcal Pneumococcal Immunocompetent ≥ 65 yo, chronic illness and immunocompromised ≤ 64 yoImmunocompetent ≥ 65 yo, chronic illness and immunocompromised ≤ 64 yo

31. Pneumonia in Children: Dx  Symptoms Infants: non-specific manifestations Infants: non-specific manifestations Fever, poor feeding, irritability, vomiting, diarrhea, URI Sx, cough, respiratory distressFever, poor feeding, irritability, vomiting, diarrhea, URI Sx, cough, respiratory distress Older children: more specific Older children: more specific Fever, cough, chest pain, tachypnea, tachycardia, grunting, nasal flaring, retracting. Cyanosis usually very late.Fever, cough, chest pain, tachypnea, tachycardia, grunting, nasal flaring, retracting. Cyanosis usually very late.  Signs/Physical exam RR > 60 for all ages RR > 60 for all ages Hypoxia Hypoxia Rales, wheezes, crackles, coarse breath sounds Rales, wheezes, crackles, coarse breath sounds

32. Pneumonia in Children: Pathogens  0-4 wks: GBS, GN enterics, Listeria  4-12 wks: C. trachomatis, GBS, GN enterics, Listeria, viral (RSV/parainfluenza), B. pertussis  3 mos-4 yrs: Viral, S. pneumo, H. influenza, M. catarrhalis, Grp A Strep, Mycoplasma  > 5yrs: Mycoplasma (5-15yrs), C. pneumo, S. pneumo, viral

33. Pneumonia in the Elderly  Prevention important  Presentation can be subtle  Antibiotic choice in CAP is same as other adults  Healthcare associated pneumonia Consider S. aureus (skin wounds) and GN bacteria (aspiration) Consider S. aureus (skin wounds) and GN bacteria (aspiration) Pneumonia in Older Residents of Long-term Care Facilities. AFP 2004; 70: 1495-1500.Pneumonia in Older Residents of Long-term Care Facilities. AFP 2004; 70: 1495-1500.

34. Pneumonia in Immunocompromised Pts  Smokers, alcoholics, bedridden, immuno- compromised, elderly  Common still common S. pneumo S. pneumo Mycoplasma Mycoplasma  Pneumocystis Carinii Pneumonia P. jirovecii P. jirovecii Fever, dyspnea, non-prod cough (triad 50%), insidious onset in AIDS, acute in other immunocompromised Pts Fever, dyspnea, non-prod cough (triad 50%), insidious onset in AIDS, acute in other immunocompromised Pts CXR: bilateral interstitial infiltrates CXR: bilateral interstitial infiltrates Steroids for hypoxia Steroids for hypoxia TMP-SMZ still first line TMP-SMZ still first line