1. Community Acquired Pneumonia Prof. Adel Khattab, MD, FCCP Prof. & Head Of Pulmonary Medicine Dept. Ain Shams University Advisor of the MOH for Chest Diseases & Aviian Flu

2. Definition Community-acquired pneumonia (CAP) is a common respiratory disease with clinical outcomes ranging from mild illness with rapid and complete recovery to a fulminate clinical course with serious complications or death.

3. Impact of CAP 3-4 Million cases annually 3-4 Million cases annually 10 Million physician visits 10 Million physician visits 600,000 Hospitalizations 600,000 Hospitalizations 45,000 Deaths 45,000 Deaths 64 Million days of restricted activity 64 Million days of restricted activity Most common cause of death from infection Most common cause of death from infection 6th Most common cause of death overall 6th Most common cause of death overall

4.  Conventional diagnostic testing for CAP is imperfect e.g role of sputum isolates in diagnosing aetiology of LRTI is controversial (colonization)  No sufficiently rapid and accurate battery of diagnostic tests for CAP are available presently  Etiology remains unknown in up to 50% of cases  However, local knowledge of likely pathogen is imperative Carroll KC. J Clin Micro 2002;40:3115-3120 Bartlett et al. NEJM 1995;333:1618-1624 Niederman et al. Am J Respir Crit Care Med 2001;163:1730-1754 ETIOLOGY OF CAP

5. Etiology of Community- Acquired Pneumonia W S Lim,J T Macfarlane, et al. Thorax 2001;56:296-301

6. Proportion of Cases (%) Key Pathogens Associated with Community- Acquired Pneumonia (CAP) – Europe (5,961 Adult Hospitalized CAP Patients in 26 Prospective Studies from 10 European Countries) Atypicals: 25% Woodhead MA. Chest 1998;113:183S–187S

8. Aspiration Pneumonia The bacteriology of aspiration pneumonia arising in the community setting has been confusing, and the exact role of anaerobes is uncertain. The bacteriology of aspiration pneumonia arising in the community setting has been confusing, and the exact role of anaerobes is uncertain. Thus, the level of involvement of enteric Gram-negative pathogens in aspiration- related illnesses is quite high and must be considered when selecting therapy. Thus, the level of involvement of enteric Gram-negative pathogens in aspiration- related illnesses is quite high and must be considered when selecting therapy.

10. RESISTANCE PROFILES OF RESPIRATORY TRACT PATHOGENS RESISTANCE PROFILES OF RESPIRATORY TRACT PATHOGENS

11. 1980s Penicillin Resistance with Streptococcus pneumoniae in the United States 0 5 10 15 20 25 30 35 40 1979-871988-891990-911992-931994-951997-981999-00 Percent Resistant (MICs  2) Intermediate (MICs 0.12-1) 558948752479915271601153119401828 351517193034334544 2001-02 1990s 2002-03 2000s Doern, AAC 2001;45:1721 and unpublished data

12. “ misuse of penicillin could lead to selection and propagation of mutant forms of bacteria resistant to the drug ” Alexander Flemming 1945

13.  Egypt Strept. Pneumoniae Penicillin resistance 38% Erythromycin resistance 55% Clindamycin resistance 51% Co-trimoxazole resistance 38% Ceftrixone resistance 16% Vancomycin resistance 0% Middle East El Kholy A, et al. Journal of antimicrobial Chemotherapy (2003) 51. 625 -630

14.  Multiple resistance in S.pneumoniae of particular concern  More recently, clinical isolates of S.pneumoniae with high- level resistance to cefotaxime and ceftriaxone have been reported  Emerging fluoroquinolone resistance although currently uncommon in most parts of the world RESISTANCE PROFILES RESISTANCE PROFILES

15. In Vitro Antibiotic Resistance Thornsberry C, et al. Antimicrob Agents Chemother. 1999;43:2612-23. Jacobs MR, et al. Antimicrob Agents Chemother. 1999;43:1901-8. Penicillin-resistant S pneumoniae 19871997  -Lactamase-producing H influenzae 19861996  -Lactamase-producing M catarrhalis 1996

16. The Disease Process Definition: Signs/symptoms of acute infection plus acute infiltrate or auscultatory findings Definition: Signs/symptoms of acute infection plus acute infiltrate or auscultatory findings Signs and symptoms: chill and/or fever, pleuritic chest pain, productive cough, tachypnea, tachycardia, rales and/or consolidation Signs and symptoms: chill and/or fever, pleuritic chest pain, productive cough, tachypnea, tachycardia, rales and/or consolidation Clinical sequelae: bacteremia, metastatic foci of infection, death Clinical sequelae: bacteremia, metastatic foci of infection, death No association between signs/symptoms and bacterial etiology No association between signs/symptoms and bacterial etiology Bartlett JG, et al. Clin Infect Dis. 2000;31:347-82. Donowitz GR, Mandell GL. Principles and Practice of Infectious Diseases 1995:619-37. Fang GD, et al. Medicine (Baltimore). 1990;69:307-16.

17. PNEUMONIA TYPICAL Sudden onset Sudden onset Productive,purulent or bloody sputum Productive,purulent or bloody sputum High fever High fever Evident local signs Evident local signs Myalgia & headache uncommon Myalgia & headache uncommon Focal alveolar or lobar infiltrates in CXR Focal alveolar or lobar infiltrates in CXR Leucocytosis is common Leucocytosis is common ATYPICAL Gradual onset Nonproductive or only scant mucoid sputum Low-grade fever Minimal local signs Myalgia & headache common Diffuse interstitial infiltrates in CXR Leucocytosis is uncommon

18. Diagnostic Algorithm for CAP Office History and physical examination Consider chest X-ray Treat empirically Emergency Room History and physical examination Chest X-ray: CBC and diff; oximetry chemistry; ABG Nursing Home History and physical examination Consider chest X-ray Treat empirically Ward + ± – + ICU + – + Blood culture Sputum Gram stain and culture Serology Thoracentesis Legionella urinary antigen testing If necessary

19. Serum Markers To Predict CAP Outcomes The two serum markers that have been most widely studied for this purpose are CRP and PCT. In general, both measures have been used to correlate with outcomes, but more data have recently been collected with PCT, and the most exciting finding has been that serial measures correlate not only with outcomes, but may also be useful for guiding the duration of therapy.

20. Low levels in outpatients could indicate that it is safe to withhold antibiotic therapy. Low levels in outpatients could indicate that it is safe to withhold antibiotic therapy. Serial measurements of PCT have also been used to define prognosis in patients with severe CAP. Serial measurements of PCT have also been used to define prognosis in patients with severe CAP.

21. Slide no21 Community-acquired pneumonia – clinical management Diagnosis of community-acquired pneumonia Severe – requires hospital treatment Mild to moderate – can be treated in the community Empirical antibiotic treatment Follow-up patient for 24–36 hours and change treatment if necessary* Assess severity of infection *not all cases of community-acquired pneumonia are caused by bacteria

22. Pneumonia PORT Prediction Rule for Mortality Risk Assessment Fine MJ, et al. N Engl J Med. 1997;336:243-50. STEP 1 Is the patient > 50 years of age? Does the patient have any of the following coexisting conditions?: Neoplastic disease; congestive heart failure; cerebrovascular disease; renal disease; liver disease Does the patient have any of the following abnormalities?: Altered mental status; pulse  125/min; respiratory rate  30/min; systolic blood pressure < 90 mm Hg; temperature < 35ºC or  40ºC No STEP 2 Assign points for: Demographic variables Comorbid conditions Physical observations Laboratory and radiographic findings Class I No Yes Class III (71-90 points) Class IV (91-130 points) Class V (> 130 points) Class II (  70 points)

23. Risk - Class Mortality Rates Risk Class Points Cohort Site of % Mortality Care % Mortality Care I Absence of 0.1% OUT I Absence of 0.1% OUT Predictors Predictors II  70 0.6% OUT II  70 0.6% OUT III 71-90 2.8% OUT or III 71-90 2.8% OUT or brief IN brief IN IV 91-130 8.2% IN IV 91-130 8.2% IN V >130 29.2% IN V >130 29.2% IN

24. Lim et al. Thorax, 2003 23 or more Group 2 Mortality intermediate (9.2%) (n=184; died = 17) 0 or 1 Group 3 Mortality high (22%) (n=210; died = 47) Group 1 Mortality low (1.5%) (n=324; died = 5) Likely suitable for home treatment Consider hospital supervised treatment Options may include a) short stay inpatient b) hospital supervised outpatient Manage in hospital as severe pneumonia Assess for ICU admission especially if CURB-65 score = 4 or 5 Any of: Confusion Urea >7 mmol/l Respiratory rate  30/min Blood pressure (SBP <90 mmHg or DBP  60 mmHg) Age  65 years CURB-65 score Treatment options

27. IDSA / ATS Guidelines for CAP in Adults, 2007

28. IDSA / ATS Consensus Guidelines on the Management of CAP in Adults 2007

29. 29 Advantages of Guidelines Synthesize large amounts of information Synthesize large amounts of information Define the strength of existing data (evidence grading) Define the strength of existing data (evidence grading) Discuss and define relevant management issues, providing an orderly approach Discuss and define relevant management issues, providing an orderly approach Help guide accurate initial empiric therapy Help guide accurate initial empiric therapy Provide a standard against which care can be evaluated Provide a standard against which care can be evaluated Focus on cost-effective management Focus on cost-effective management Identify defects in knowledge base to direct future research Identify defects in knowledge base to direct future research Tool to improve patient outcomes Tool to improve patient outcomes

30. 30 Concerns About Guidelines Management without thought Management without thought Deviations may be basis for discipline Deviations may be basis for discipline If experts cannot all agree, how can we have accurate guidelines? If experts cannot all agree, how can we have accurate guidelines? What do we do if the existing knowledge base is of poor quality? What do we do if the existing knowledge base is of poor quality? How strong should new data be before changing and updating guidelines? How strong should new data be before changing and updating guidelines?

31. Inpatient Community-Acquired Pneumonia Guideline Adherence Improves Mortality Mortensen EM, et al. Am J Med. 2004;117:726-731. Days from Presentation Probability of Survival 0.75 0.80 0.85 0.95 0.90 1.00 0 10 20 30 Guideline-Concordant Antibiotics (n=323) Nonguideline-Concordant Antibiotics (n=97)

32. 32 Community-Acquired Pneumonia Guidelines Implementation: Why? Lower (30-day) mortality Lower (30-day) mortality  5-year study of 28,700 patients (OR 0.69)  Spanish hospital: survival rate higher (OR 2.14) Hospitalization Hospitalization  Pneumonia Severity Index: fewer less-ill patients admitted (49% vs 31%)  American Thoracic Society (1993): hospital-rate decreased (13.6% vs 6.4%) Cost Cost  Decreased by half (P=0.01) Comprehensive protocol is greater than a single element Comprehensive protocol is greater than a single element Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72.

34. Implementation of Guideline Recommendations Locally adapted guidelines should be implemented to improve process of care variables and relevant clinical outcomes. (Strong recommendation; level I evidence.)

35. Management of CAP: Site-of-Care Decisions Hospitalization ? ICU admission?

36. Assess the ability to safely and reliably take oral medication & the availability of outpatient support resources

40. Hospital admission decision Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment. (Strong recommendation; level I evidence.)

41. Hospital admission decision For patients with CURB-65 scores 2, more- intensive treatment—that is, hospitalization or, where appropriate and available, intensive in- home health care services—is usually warranted. (Moderate recommendation; level III evidence.)

42. ICU admission decision. Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence.) Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in next table. (Moderate recommendation; level II evidence.)

45. Diagnostic Testing In addition to a constellation of suggestive clinical features, a demonstrable infiltrate by chest radiograph or other imaging technique, with or without supporting microbiological data, is required for the diagnosis of pneumonia. (Moderate recommendation; level III evidence.)

46. Routine diagnostic tests to identify an etiologic diagnosis are optional for outpatients with CAP. (Moderate recommendation; level III evidence.) Recommended diagnostic tests for etiology

47. Pretreatment blood samples for culture and an expectorated sputum sample for stain and culture (in patients with a productive cough) should be obtained from hospitalized patients with the clinical indications listed in the next table but are optional for patients without these conditions. (Moderate recommendation; level I evidence.) Recommended diagnostic tests for etiology (cont.) (cont.)

48. Chest X-ray Can help to diagnose pneumonia Can help to diagnose pneumonia Can’t determine pathogen Can’t determine pathogen Helps to determine severity Helps to determine severity  multilobar  Cavities  Pleural effusion.

49. Consolidation, Focal opacity S pneumoniae H influanzae Atypical

50. Interstitial / Miliary Viral Mycoplasma M TB Fungi

51. Bil. hilar lymphadenopathy and nodular opacities M TB Atypical Viral

52. Cavity: Staph aureus, Klebsiella, Anaerobes, M TB

53. Sputum Gram Stain & Culture Neither sensitive nor specific Neither sensitive nor specific 30% of patients can’t produce sputum 30% of patients can’t produce sputum With grading—only 25%-40% good quality With grading—only 25%-40% good quality At best 28% are good samples At best 28% are good samples Can’t detect atypicals Can’t detect atypicals Prior antibiotics affect results Prior antibiotics affect results

54. Limitations of Sputum Culture Overdiagnosis Overdiagnosis - Contamination with upper respiratory tract flora - Chronic colonization of the lower respiratory tract with pathogens Underdiagnosis - Sampling errors - Atypical bacterial pathogens

55. Blood Cultures Outpatient – < 1% Outpatient – < 1% Ward patients – 6.6%-17.6% Ward patients – 6.6%-17.6% ICU patients – 27% ICU patients – 27% Recommended for hospitalized patients Recommended for hospitalized patients It has a low sensitivity but high specificity It has a low sensitivity but high specificity

56. Serology Need paired assessments (acute & convalescent) Need paired assessments (acute & convalescent) Results not available at time of initial treatment decision Results not available at time of initial treatment decision Not recommended for routine use Not recommended for routine use

57. Laboratory diagnosis of C. pneumoniae infections FeatureCultureDFAPCRSerology -------------------------------------------------------------------------------------- DetectionInfectiousAntigenDNAAntibodies organism SpecimenThroat SwabThroat SwabThroat Swab Blood BALBALBALSputum ? Blood ? Sensitivity50%20-60%85-90% 60-80% Specificity100%70-95%95-100% 90-100%

58. Waterer GW, et al. Am J Med. 2001;110:41-8; Murdoch DR. CID 2003;36:64-9 Diagnostic Tests for Legionella and CAP TestSpecimenSensitivitySpecificityTime to diagnosis CultureSputum< 10-80%100%3-7 days Blood0%-6%100%3-7 days Direct fluorescentSputum33%-68%>95%1 hour antibody screen Antigen detectionUrine80%-90%>99% 99%< 1 hour SerologySerum60%-80%>95%6-10 weeks PCRUrine/blood75%-82%90%-100%2-4 hours Respiratory83%-100%90%-100%2-4 hours secretions

59. Invasive Procedures Fulminant course Fulminant course Unresponsiveness to standard antimicrobials Unresponsiveness to standard antimicrobials Thoracentesis if effusion > 10 mm on lateral decubitus Thoracentesis if effusion > 10 mm on lateral decubitus

60. Invasive diagnostic techniques Bronchoscopy with a protected brush catheter Bronchoscopy with a protected brush catheter Bronchoalveolar lavage with or without balloon protection Bronchoalveolar lavage with or without balloon protection Direct needle aspiration of the lung Direct needle aspiration of the lung Thoracocentesis Thoracocentesis

61. Characteristics of Empyema Pleural fluid. Pleural fluid. PH < 7.1 PH < 7.1 WBC > 10,000 cells / mm 3 WBC > 10,000 cells / mm 3 Low glucose Low glucose Culture or Gram stain demonstrating organisms Culture or Gram stain demonstrating organisms

62. Pretreatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained and quality performance measures for collection, transport, and processing of samples can be met. (Moderate recommendation; level II evidence.) Recommended diagnostic tests for etiology

63. Patients with severe CAP, as defined above, should at least have blood samples drawn for culture, urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae performed, and expectorated sputum samples collected for culture. For intubated patients, an endotracheal aspirate sample should be obtained. (Moderate recommendation; level II evidence.) Recommended diagnostic tests for etiology (cont.)

65. Serum Markers To Predict CAP Outcomes The two serum markers that have been most widely studied for this purpose are CRP and PCT. In general, both measures have been used to correlate with outcomes, but more data have recently been collected with PCT, and the most exciting finding has been that serial measures correlate not only with outcomes, but may also be useful for guiding the duration of therapy.

66. 66 Reasons to Perform Diagnostic Testing Confirm the presence of community-acquired pneumonia: chest radiograph, serum markers Confirm the presence of community-acquired pneumonia: chest radiograph, serum markers Establish an etiologic diagnosis Establish an etiologic diagnosis  Proper therapy: look for unusual or resistant pathogens  Epidemiologic purposes: eg, Legionella spp and environmental source, design of future empiric treatment  Focused and tailored therapy: proper duration, de-escalate, escalate Determine severity and prognosis: bacteremia, procalcitonin, C-reactive protein Determine severity and prognosis: bacteremia, procalcitonin, C-reactive protein Define duration of therapy: procalcitonin Define duration of therapy: procalcitonin

67. 67 Reasons NOT to Perform Diagnostic Testing Expensive Expensive Time consuming Time consuming May delay therapy May delay therapy Low yield of true positives: role of prior antibiotics Low yield of true positives: role of prior antibiotics False positive may add to overuse of antibiotics False positive may add to overuse of antibiotics False negatives may lead to undertreatment False negatives may lead to undertreatment Mixed infection (atypicals) may not be detected, yet needs therapy Mixed infection (atypicals) may not be detected, yet needs therapy No effect on outcome No effect on outcome

68. 68 Recommended Testing When Community- Acquired PneumoniaIs Suspected Diagnose with chest x-ray and clinical data 1,2 Diagnose with chest x-ray and clinical data 1,2 Look for specific pathogens that alter therapy based on historical and epidemiologic clues 1 Look for specific pathogens that alter therapy based on historical and epidemiologic clues 1 Laboratory tests for hospitalized patients include arterial blood gas and basic blood chemistry (ie, red and white blood cell count, creatinine and urea nitrogen, aminotransferases, sodium, and potassium) 2 Laboratory tests for hospitalized patients include arterial blood gas and basic blood chemistry (ie, red and white blood cell count, creatinine and urea nitrogen, aminotransferases, sodium, and potassium) 2 Blood cultures with severe illness 1,2 Blood cultures with severe illness 1,2 Sputum Gram-stain and culture prior to therapy IF good quality, rapid transport, and processing in lab 1,2 Sputum Gram-stain and culture prior to therapy IF good quality, rapid transport, and processing in lab 1,2 Legionella spp and pneumococcal urinary antigen for severe community-acquired pneumonia (CAP) 1,2 Legionella spp and pneumococcal urinary antigen for severe community-acquired pneumonia (CAP) 1,2 Endotracheal aspirate or sputum culture for severe CAP 1,2 Endotracheal aspirate or sputum culture for severe CAP 1,2 1. Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72. 2. Woodhead M, et al. Eur Respir J. 2005;26:1138-1180.

69. 69 Community-Acquired Pneumonia Guidelines: Urinary Antigen Testing Role of urinary antigen testing 1 Role of urinary antigen testing 1  Pneumococcal  Sensitivity 50%–80%  Specificity >90%  Legionella spp  Serogroup 1 (accounts for most) May not change therapy for most patients 1 May not change therapy for most patients 1 Macrolide/atypical pathogen coverage included in empiric therapy recommendations 1 Macrolide/atypical pathogen coverage included in empiric therapy recommendations 1 Serogroup 1 urinary antigen testing is recommended for patients with severe community-acquired pneumonia and in other patients where this infection is clinically or epidemiologically suspected 1,2 Serogroup 1 urinary antigen testing is recommended for patients with severe community-acquired pneumonia and in other patients where this infection is clinically or epidemiologically suspected 1,2 1. Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72. 2. Woodhead M, et al. Eur Respir J. 2005;26:1138-1180.

70. Therapy

71. Therapy Fluid / dietFluid / diet AntipyreticsAntipyretics Cough syrupCough syrup O 2 therapyO 2 therapy TTT of complications & Coexisting illnessTTT of complications & Coexisting illness Antibiotic General & supportive

72. CAP: When to start empiric therapy? As soon as possible in ED As soon as possible in ED CAP: delay-to-AB> 4h after arrival CAP: delay-to-AB> 4h after arrival  Increased mortality  Increased LOS IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72

73. 1 Previously healthy and no risk factors for drug- resistant S. pneumoniae (DRSP) infection: a) Macrolides (Azithromycin, clarithromycin or erythromycin) (strong recommendation; level I evidence) b) Doxycycline (weak recommendation; level III evidence) IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72 Outpatient Recommended empirical antibiotics for CAP: Outpatient

74. 2. Presence of comorbidities such as heart, lung, or renal disease, diabetes, alcoholism, malignancies, Asplenia, immunosuppressing conditions or drugs; Antibiotic Use in last 90 days, or other risks of DRSP infection heart, lung, or renal disease, diabetes, alcoholism, malignancies, Asplenia, immunosuppressing conditions or drugs; Antibiotic Use in last 90 days, or other risks of DRSP infection a) Respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) (strong recommendation; level I evidence) b) B-lactam plus a macrolide (strong recommendation; level I evidence) IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72 Outpatient Recommended empirical antibiotics for CAP: Outpatient

75. Presence of comorbidities a) B-lactam plus a macrolide High-dose amoxicillin [e.g. 1 g 3 times daily] or Amoxicillin-clavulanate [2 g 2 times daily] Alternatives: Ceftriaxone, Cefpodoxime & Cefuroxime, Doxycycline alternative to macrolide IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72 Outpatient Recommended empirical antibiotics for CAP: Outpatient

76. Outpatient Treatment Previously healthy and no risk factors for drug- resistant S. pneumoniae (DRSP) infection: A) Macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence) B) Doxycycline (weak recommendation; level III evidence)

77. 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 (in which case an alternative from a different class should be selected); or other risks for DRSP infection: Outpatient Treatment (cont.)

78. A. A respiratory fluoroquinolone (levofloxacin, moxifloxacin or gemifloxacin,) (strong recommendation; level I evidence) B. A b-lactam plus a macrolide (strong recommendation; level I evidence) (High-dose amoxicillin [e.g., 1 g 3 times daily] or amoxicillin-clavulanate [2 g 2 times daily] is preferred; alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily]; doxycycline [level II evidence] is an alternative to the macrolide.) Outpatient Treatment (cont.)

79. 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 in recommendation 16 for any patient, including those without comorbidities. (Moderate recommendation; level III evidence.) Outpatient Treatment (cont.)

80. Recommended empirical antibiotics for CAP: Inpatient, Non-ICU ttt a) Respiratory fluoroquinolone (strong recommendation; level I evidence) b) b-lactam plus a macrolide Cefotaxime, Ceftriaxone, Ampicillin, or Ertapenem Cefotaxime, Ceftriaxone, Ampicillin, or Ertapenem (strong recommendation; level I evidence) Doxycycline as an alternative to the macrolide. Doxycycline as an alternative to the macrolide. (weak recommendation; level III evidence) IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72

81. Inpatient, non-ICU treatment A respiratory fluoroquinolone (strong recommendation; level I evidence) A b-lactam plus a macrolide (strong recommendation; level I evidence) (Preferred b-lactam agents include cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; with doxycycline [level III evidence] as an alternative to the macrolide. A respiratory fluoroquinolone should be used for penicillin-allergic patients.)

82. Inpatient, ICU treatment A b-lactam (cefotaxime, ceftriaxone, or ampicillin- sulbactam) plus either azithromycin (level II evidence) or a fluoroquinolone (level I evidence) (strong recommendation) (For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are recommended.)

83. 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 (for penicillin-allergic patients, substitute aztreonam for the above b-lactam). (Moderate recommendation; level III evidence.) Inpatient, ICU treatment

84. For community-acquired methicillin-resistant Staphylococcus aureus infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence.) Inpatient, ICU treatment

85. Recommended empirical antibiotics for CAP: Inpatient, ICU ttt A) b-lactam plus either azithromycin or a respiratory fluoroquinolone A) b-lactam plus either azithromycin (level II evidence) or a respiratory fluoroquinolone (strong recommendation; level I evidence) (cefotaxime, ceftriaxone, or ampicillin-sulbactam) (cefotaxime, ceftriaxone, or ampicillin-sulbactam) IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72

86. If Pseudomonas is a considerationIf Pseudomonas is a consideration Antipseudomonal b-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) + either ciprofloxacin or levofloxacin (750- mg dose) Or The above b-lactam + aminoglycoside & azithromycin Or The above b-lactam + aminoglycoside & an antipneumococcal fluoroquinolone IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72 Inpatient, ICU ttt Recommended empirical antibiotics for CAP: Inpatient, ICU ttt

87. Community Acquired MRSA (CA-MRSA)Community Acquired MRSA (CA-MRSA) If CA-MRSA is a consideration add vancomycin or linezolid add vancomycin or linezolid IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72 Inpatient, ICU ttt Recommended empirical antibiotics for CAP: Inpatient, ICU ttt

88. Pathogen-directed therapy Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at that pathogen. (Moderate recommendation; level III evidence.)

89. Switch from intravenous to oral therapy. Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract. (Strong recommendation; level II evidence.)

90. Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary. (Moderate recommendation; level II evidence.) Switch from intravenous to oral therapy.

91. Approaches to Switching from IV to oral therapy 1.Step – down therapy:  Conversion from one antibiotic given IV to another given orally. 2.Transitional – therapy:  Conversion from same antibiotic given IV to oral but not at the same dosage or strength. 3.Sequential – therapy:  Conversion from same antibiotic IV to oral at the same dosage and strength.

92. CAP: Duration of Therapy “A minimum of 5 days… Afebrile for 48-72 h … “A minimum of 5 days… Afebrile for 48-72 h (level I evidence), … No more than1 CAP- associated sign of Clinical instability “ IDSA /ATS Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72

93. A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extra-pulmonary infection, such as meningitis or endocarditis. (Weak recommendation; level III evidence.) Duration of antibiotic therapy

94. Considerations for patients worsening or failing to improve by day three Predisposing condition requiring >3 days for improvementPredisposing condition requiring >3 days for improvement (continue present Rx) e.g. elderly patient Incorrect diagnosis or complicating conditionIncorrect diagnosis or complicating condition Common: Pulmonary embolism or infarction, carcinoma, pulmonary edema, bronchiectasis, etc. Common: Pulmonary embolism or infarction, carcinoma, pulmonary edema, bronchiectasis, etc. Uncommon: Pulmonary eosinophilia, alveolar hemorrhage, foreign body Uncommon: Pulmonary eosinophilia, alveolar hemorrhage, foreign body Unexpected pathogens: eg, mycobacteria, MRSA etc. Unexpected pathogens: eg, mycobacteria, MRSA etc.

95. Duration of antibiotic therapy Patients with CAP should be treated for a minimum of 5 days (level I evidence), should be afebrile for 48–72 h, and should have no more than 1 CAP-associated sign of clinical instability (next table) before discontinuation of therapy (Moderate recommendation, level II evidence)

97. Management of Non-responding Pneumonia Definitions and classification The use of a systematic classification of possible causes of failure to respond, based on time of onset and type of failure, is recommended. (Moderate recommendation; level II evidence.)

98. 98 Community-Acquired Pneumonia Guidelines, US: Nonresolving Failure to improve Failure to improve  Early (<72 hours): normal  Delayed  Resistant organism  Effusion/empyema  Superinfection  Noninfectious Bronchitis obliterans- organized pneumoniaBronchitis obliterans- organized pneumonia Pleural effusion (PE)Pleural effusion (PE) Congestive heart failureCongestive heart failure Drug feverDrug fever Deteriorate/progression Deteriorate/progression  Early: illness severity  Organism resistance  Metastatic infection  PE, adult respiratory distress syndrome, vasculitis  Delayed  Superinfection  Comorbid exacerbation  Noninfectious complications PE, myocardial infarction, renal failurePE, myocardial infarction, renal failure Management Management  Transfer to higher care level  More diagnostic testing  Escalate/change treatment Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72.

100. THANK YOU