1. COMMUNITY-ACQUIRED PNEUMONIA (CAP) Pulmonary Medicine Department Ain Shams University http:// telemed.shams.edu.eg/moodle5

2. At the end of this lecture the student should be able to: 1.Describe the clinical types of pneumonias. 2.Know the definition of community acquired pneumonia. 3.Know the impact, mortality, epidemiology and etiology of community acquired pneumonia. 4.Describe the pathogenesis. 5.Discuss the classification of community acquired pneumonia. 6.Know the clinical presentation.

3. 7.Interpret the investigations for community acquired pneumonia. 8.Propose the suitable antibiotic therapy. 9.Explain the indications for hospitalization and icu admission. 10.Know the role of immunization in community acquired pneumonia. 11.Discuss the non-infectious pneumonitis. 12.Explain the causes of treatment failure. 13.Discuss the causes of recurrent pneumonia.

4. Clinical types of pneumonia: Community- acquired pneumonia (CAP). Hospital-acquired (nosocomial) pneumonia (HAP). Pneumonia in immunocompromised host including AIDS patients. Aspiration pneumonia. Recurrent pneumonia.

5. Community-Acquired Pneumonia Is a parenchymal lung infection which develops outside the hospital without iatrogenic or invasive procedure.

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

7. Mortality of Community-acquired pneumonia Mortality in home-treated patients <1% Mortality in hospital-treated patients 5-15%. Mortality in ICU-treated patients 20-50%.

8. EPIDEMIOLOGY Risk factors for developing Pneumonia cigarette smoking advanced age dementia malnutrition splenectomized patient previous episode of pneumonia chronic bronchitis chronic illnesses

9.  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

10. Organsims causing CAP: Streptococcus pneumoniae40-60% Haemophilus influenzae10% Respiratory viruses10-15% Mycoplasma pneumoniae5-15% Legionella species5-10% Chlamydia pneumoniae5-10% Gram negative bacilli5% Staphylococcus aureus5% Moraxella catarrhalis<5% Mycobacterium tuberculosis<5%

11. LaForce. Clin Infect Dis 1992;14 (Suppl. 2):S233–7 Mycoplasma (6.7%) Other bacteria (12.5%)Viral (12.6%) H. influenzae (14.3%) S. pneumoniae (44.9%) Chlamydia (3.7%) Legionella (5.2%) Analysis of 16 studies of >3300 hospitalized patients (1960–1987) Etiology of community- acquired pneumonia

12.  S.pneumoniae is the commonest  Next largest group: M.pneumoniae and C.pneumoniae  Viruses cause approximately 10% of pneumonias, but secondary infection with S.pneumoniae, H.influenzae or other bacteria develops in about half P rout et al. S Afr Med J 1983:64:443-446 Myburgh et al. J Antimicrob Chemother 1993;31:suppl, 163-169 YOUNG ADULTS WITHOUT CO-MORBID ILLNESS

13.  H.influenzae is usually considered an important pathogen in patients with chronic lung disease but may occur in normal lungs and accounts for 5-10% of pneumonia acquired in the community  Pulmonary TB may present as an acute CAP in endemic areas Prout et al. S Afr Med J 1983:64:443-446 YOUNG ADULTS WITHOUT CO-MORBID ILLNESS

14.  Pneumococcus is the most common organism (40-60% of cases)  Respiratory viruses, H.influenzae and Gram-negative bacilli occur with increased frequency  Higher prevalence of Gram-negative infections is due to increased colonization of upper and lower respiratory tract, especially in those with underlying disorders  M.TB shown to be a particular problem in old-age homes Fein et al. Clin Chest Med 1991;12:319-336 ELDERLY PATIENTS WITH/WITHOUT COMORBIDITY

15.  The incidence of “atypical infections” in most countries is uncertain  Are we looking for them ?  In an South African study L. pneumophila was diagnosed in 20% of cases of pneumonia of documented causation (12% of all cases)  Another study suggested that “atypical” pathogens may account for between 20-40% of cases in hospitalized adults Myburgh et al. J Antimicrob Chemother 1993;31:suppl, 163-169 Maartens et al. S Afr Med J 1994;84:678-682 ROLE OF ATYPICALS IN CAP

16.  M.pneumoniae: ~ Proportion varies geographically worldwide and from year to year, endemic and epidemic ~ 34 % school-going children and young adults (2-14yr) (Milan) ~ vs. infants (33% <1yr) and preschool (23% 1-5yr) (Jeddah) ~ Up to 17% of cases >40 yr Principi et al. Clin Infect Dis 2001;32:1281-1289 Madani TA, Al-Ghamdi AA. MBC Infect Dis 2001;1:6-10 Murray et al. Arch Pathol Lab 1986;110:34-41 ROLE OF ATYPICALS IN CAP

17.  C.pneumoniae: ~ 14% of children 2-14 yrs hospitalized with LRTI (Milan) ~ 45% of children 1mo-15yr (Bangkok; 88% < 5yr old) ~ May be part of a co-infection with other bacteria in up to 30% of cases Principi et al. Clin Infect Dis 2001;32:1281-1289 Likitnukul et al. Ped Infect Dis J 2003;22:749-780 Ruiz-Gonzalez et al. Am J Med 1999;106:385-390 ROLE OF ATYPICALS IN CAP

18.  Legionella spp: ~ Geographical and seasonal variations seen in CAP incidence studies ~ Usually ranks 2 nd to pneumococcus in severe CAP ~ Predisposed by organ-transplant patients, smokers, renal failure or chronic lung disease ROLE OF ATYPICALS IN CAP Stout et al. NEJM 1197;337:682-687 Roig et al. Chest 1994;105:1817-1825

19. 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

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

21.  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

22. Clinical picture of pneumonia Respiratory symptoms: Cough Sputum Dyspnea Chest pain URT Haemoptysis Non-respiratory symptoms: Vomiting Confusion Diarrhea Rash Abdominal pain Signs: Fever Tachypnea Tachycardia Consolidation Confusion Hypotension

23. Differential Diagnosis of Pneumonia Pulmonary infarction. Atypical pulmonary oedema. Subphrenic abscess or pancreatitis. Pulmonary eosinophilia. Bronchoalveolar cell carcinoma. Primary and secondary lung tumors.

24. PNEUMONIA TYPICAL Sudden onset Productive,purulent or bloody sputum High fever Evident local signs Myalgia & headache uncommon Focal alveolar or lobar infiltrates in CXR 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

25. 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

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

27. Consolidation, Focal opacity S pneumoniae H influanzae Atypical

28. Interstitial / Miliary Viral Mycoplasma M TB Fungi

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

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

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

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

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

34. 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%

35. 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%< 1 hour SerologySerum60%-80%>95%6-10 weeks PCRUrine/blood75%-82%90%-100%2-4 hours Respiratory83%-100%90%-100%2-4 hours secretions

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

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

38. COMPLICATIONS Potential complications include parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess Parapneumonic effusions are associated with younger age (approximately two years) and a nearly universal incidence of bacteremia but do not result in poorer outcome than susceptible strains

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

40. COMPLICATIONS Bacteremia with subsequent seeding of other foci is seen in 25% of cases and represents the most significant complication. Bacteremic patients were more likely to die during the first week of illness. Splenectomized patients have an increased risk of overwhelming sepsis Abscesses are usually culture-positive and rapidly responsive to drainage Necrotizing pneumonia is culture-negative and responds adversely to interventional therapy

41. Slide no41 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

42. Criteria for hospitalization History: >65 yr, DM, renal failure, heart failure, ch. Lung disease, alcoholism, malignancy and immunosupression. Clinically: RR>30, Systolic BP<90 or Diastolic BP<60, hyperpyrexia, altered mental state and extrapulmonary site of infection. Investigation: WBC 30,000, Pa o2<60mmHg,haematocrit<30 and pleural effusion or multiple lobe or rapid spread in CXR.

43. 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

44. Antibiotic Selection for RTI The micro-organism: * Possible pathogens.* Resistant organisms. The patient: *Age.* Severity of infection. *Allergy to antibiotics.* Concomitant disease. *Pregnancy. The antibiotic: * Spectrum of activity.* Clinical efficacy. * Penetration to infection site.* Adverse effects. * Potential for resistance.* Convenience. * Drug and food interaction.* Cost.

45. 70 60 50 40 30 20 10 0 EffectiveIneffective * Therapy at 72 h Mortality (%) Impact of Antibiotic Therapy Leroy et al. Intensive Care Med, 1995

46. Outpatient Treatment of CAP North America guidelines –Macrolides –Tetracycline –Fluoroquinolone or  -lactam plus macrolide British Thoracic Society guidelines –Aminopenicillins –Macrolides

47. Inpatient Treatment of CAP North America guidelines  -lactam plus macrolide or Fluoroquinolone British Thoracic Society guidelines –Aminopenicillins + macrolide or Fluoroquinolone

48. Initial Antibiotics in CAP Better outcome with: 3 rd generation cephalosporin and macrolide 2 nd generation cephalosporin and macrolide Fluoroquinolone alone Worse outcome with: ß-lactam/ß-lactamase inhibitors plus macrolide Aminoglycoside and any other agent Gleason et al. Arch Int Med 1999

49. CAP — out-patient therapy/nursing home residents Canadian guidelines, 2000 No risk factorsModifying factors present (a)(b) Macrolide 2nd generation macrolide Respiratory fluoroquinolone OR amox/clav  macrolide doxycycline 2nd generation cephalosporin (a) COPD but no steroids within 3 months (b) COPD, oral steroids, antibiotics within 3 months OR  macrolide

50. CAP — hospitalised, ward managed OR Respiratory fluoroquinolone a 2nd/3rd/4th generation cephalosporin + macrolide a Either levofloxacin + clindamycin, or trovafloxacin if aspiration suspected Canadian guidelines, 2000

51. CAP — ICU managed Ciprofloxacin a + antipseudomonal  -lactam b OR antipseudomonal  -lactam + aminoglycoside + macrolide or 4th generation fluoroquinolone a Add clindamycin if aspiration suspected b Ceftazidine, piperacillin/tazobactam, imipenem or meropenem Canadian guidelines, 2000

52. IDSA GUIDELINES Clinical Infectious Diseases 2007;37:1405-1433

53. Patient variablePreferred treatment options Outpatient Previously healthy No recent antibiotic therapyA macrolide a or doxycycline a Recent antibiotic therapy b b A respiratory fluoroquinolone c alone, an advanced macrolide d plus high-dose amoxicillin, e or an advanced macrolide plus high-dose amoxicillin-clavulanate f c d e f Comorbidities (COPD, diabetes, renal or congestive heart failure, or malignancy) No recent antibiotic therapy An advanced macrolide d or a respiratory fluoroquinolone d Recent antibiotic therapy A respiratory fluoroquinolone c alone or an advanced macrolide plus a ß-lactam g c g Suspected aspiration with infectionAmoxicillin-clavulanate or clindamycin Influenza with bacterial superinfection A ß-lactam g or a respiratory fluoroquinolone g

54. Patient variablePreferred treatment options Inpatient Medical ward No recent antibiotic therapy A respiratory fluoroquinolone alone or an advanced macrolide plus a ß -lactam h h Recent antibiotic therapy b b An advanced macrolide plus a ß -lactam or a respiratory fluoroquinolone alone (regimen selected will depend on nature of recent antibiotic therapy) ICU Pseudomonas infection is not an issue A ß -lactam h plus either an advanced macrolide or a respiratory fluoroquinolone h Pseudomonas infection is not an issue but patient has a ß -lactam allergy A respiratory fluoroquinolone, with or without clindamycin Pseudomonas infection is an issue i i Either (1) an antipseudomonal agent j plus ciprofloxacin, or (2) an antipseudomonal agent plus an aminoglycoside k plus a respiratory fluoroquinolone or a macrolide j k Pseudomonas infection is an issue but the patient has a ß -lactam allergy Either (1) aztreonam plus levofloxacin, l or (2) aztreonam plus moxifloxacin or gatifloxacin, with or without an aminoglycoside l

55. Patient variablePreferred treatment options Inpatient Nursing home Receiving treatment in nursing home A respiratory fluoroquinolone alone or amoxicillin-clavulanate plus an advanced macrolide Hospitalized Same as for medical ward and ICU

56. Duration of therapy Total duration of treatment of CAP, may be 10-14 days or 5 days after disappearance of fever (2 weeks in legionella or Staph pneumonia ).

57. Criteria for Switch Therapy No clinical indications for continuing IV therapy. No abnormal GI absorption. Patient afebrile. Cough & respiratory distress improved. WBC returning to normal.

58. 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.

59. Response to Treatment Adequate clinical response: –Clinical improvement within 48-72 h (ATS, ERS) –Subjective response within 1-3 days (IDSA) or 3-5 days (CIDS/CTS) –Fever usually persists for longer than other signs and symptoms Clinical resolution can be delayed by: –Old age –Comorbidity –Severe infection –Other host factors Radiographic deterioration common during first several days of treatment (reflecting continued inflammatory change in absence of viable bacteria) Huchon G, et al. Eur Resp Rev. 1998;8:391-426. Bartlett JG, et al. Clin Infect Dis. 2000;31:347-82. Mandell LA, et al. Clin Infect Dis. 2000;31:383-421. American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-54.

60. Reasons for Treatment Failure Patient fails to respond or deteriorates following initial therapy Incorrect diagnosis Other conditions Congestive heart failure Embolus Neoplasm Sarcoid Drug reaction Hemorrhage Correct diagnosis Host Local factors (eg, obstruction, foreign body) Inadequate host response Complication (eg, pulmonary superinfection, empyema) Drug Error in drug selection Error in dose or route Compliance Adverse drug reaction Pathogen Drug-resistant organism Other pathogen Bartlett JG, et al. Clin Infect Dis. 2000;31:347-82.

61. Causes of recurrent pneumonia Local bronchial obstruction : Intraluminal ( foreign body ). Intramural (adenoma, carcinoma) Extramural (Compression by lymph node ) Local bronchopulmonary disease : Pulmonary sequestration Localized bronchiectasis Generalized bronchopulmonary disease : Bronchiectasis Cystic fibrosis Chronic bronchitis Immotile cilia syndrome Chronic sinusitis Non-respiratory disease : Recurrent aspiration ( neuromuscular & oesophageal problems, alcoholics, epileptics ) Immune deficiency states Gingival disease.

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