1. By Professor Of Pediatrics, Head of Allergy & Clinical Immunology Unit - Mansoura University Egypt

2. Out Line (1) Definition and Pathophysiolgoy of pneumomnia (1) Definition and Pathophysiolgoy of pneumomnia ( 2) Does the patient have a pneumonia? (3) What is the microbial etiology? (3) What is the microbial etiology? (4) Where you treat? (4) Where you treat? (5) How to treat? (5) How to treat?

3. Definition Definition It’s an infection in alveolar spaces It’s an infection in alveolar spaces (pulmonary parenchyma) leading to their Consolidation. Consolidation means the alveoli are Consolidation means the alveoli are filled with exudates and inflammatory cells with loss of their gaseous content. cells with loss of their gaseous content.

4. Pathophysiology Pathophysiology A- Development of Pneumonia: Virulent organism. Virulent organism. Immune compromised host Local Immune compromised host Local Systemic Systemic B- Pulmonary host defenses (1)Mechanical and structural:  Cough.  Mucocilliary clearance  Airway branching (configuration) continue

5. Pulmonary host defenses (2) Cellular defenses: (2) Cellular defenses:  Resident alveolar macrophages  Recruited Neutrophils occures when alveolar macrophages are over whelmed in lower respiratory tract infections. continue Pathophysiology

6. Pathophysiology (3)Humoral defenses  IgA in upper airway  IgG in lower airway (4) Inflammatory and molecular defenses:  Airway epithelium through secretion of peptides called defensins, and chemokines.  Cytokines as: IL-10,GM- CSF. continue

7. Pathophysiology Bacteria or virus gain access to respiratory tract from: Bacteria or virus gain access to respiratory tract from: 1. Inhalation of contaminated air 2. Microaspiration 3. Hematogenous seeding of the lung. Whether Pneumonia is the result of such bacterial entry depends on interaction between the bacterium (load, Virulence) and pulmonary defense mechanism. Whether Pneumonia is the result of such bacterial entry depends on interaction between the bacterium (load, Virulence) and pulmonary defense mechanism.continue

8. Pathophysiology The usual out come is ingestion of bacteria or virus by alveolar macrophages, an alternative but less common is complement mediated bacterial lyses The usual out come is ingestion of bacteria or virus by alveolar macrophages, an alternative but less common is complement mediated bacterial lyses When these mechanisms don’t destroy alveolar bacteria,polymorph nuclear leukocytes with their phagocytic capability are required with the result inflammatory response results in Pneumonia passing in 3 stages. When these mechanisms don’t destroy alveolar bacteria,polymorph nuclear leukocytes with their phagocytic capability are required with the result inflammatory response results in Pneumonia passing in 3 stages.

9. Pathology of Pneumonia: 1- Stage of congestion: (red hepatization) Due to antigen antibody reaction no Due to antigen antibody reaction no radiological findings. radiological findings. 2- Stage of gray hepatiztion: Respiratory distress and homogenous Respiratory distress and homogenous opacity in chest rdiography. opacity in chest rdiography. 3- Stage of resolution: When immune system takes upper When immune system takes upper hand, resolution and convalescence. hand, resolution and convalescence.

10. Pathology

11. Classification of Pneumonia: Two types: typical And atypical. Two types: typical And atypical. (1) Typical pneumonia (1) Typical pneumonia (2) Atypical pneumonia (2) Atypical pneumonia Another Classification: Another Classification: (1) Community- acquired pneumonia ( CAP) (1) Community- acquired pneumonia ( CAP) (2) hospital – acquired pneumonia ( nosocomial (2) hospital – acquired pneumonia ( nosocomial pneumonia) pneumonia)

12. Out Line (1) Definition and Pathophysiolgoy of pneumomnia (1) Definition and Pathophysiolgoy of pneumomnia (2) Does the patient have a pneumonia? (3) What is the microbial etiology? (3) What is the microbial etiology? (4) Where you treat? (4) Where you treat? (5) How to treat? (5) How to treat?

13. Clinical and Radiological Diagnosis of Pneumonia (1) Respiratory distress (2) Bronchial breathing or fine (2) Bronchial breathing or fine consonating creptation by consonating creptation by auscultation auscultation (3) Homogenous opacity is a cardinal (3) Homogenous opacity is a cardinal radiological sign radiological sign

14. Clinical and Radiological Diagnosis of Pneumonia  To differentiate between Bacterial and viral etiology Look for: - preceding symptoms - preceding symptoms - Fever - Fever - Para pneumonic effusion - Para pneumonic effusion - Wheezes - Wheezes - Distribution & size of homogenous - Distribution & size of homogenous opacity opacity

15. Radiology

16. Radiology

17. Out Line (1) Definition and Pathophysiolgoy of pneumomnia (2) Does the patient have a pneumonia? (3) What is the microbial etiology? (3) What is the microbial etiology? (4) Where you treat? (4) Where you treat? (5) How to treat? (5) How to treat?

18. Etiological Diagnosis  It is difficult to determine the causative organism of Pneumonia. So the treatment usually empirical based on Predicting factors for the causative organism as the following. a) Age of the patient. a) Age of the patient. b) Immune status, b) Immune status, c) Extra pulmonary manifestations. c) Extra pulmonary manifestations. * It can be confirmed by: * It can be confirmed by: Culture + Specific tests. Culture + Specific tests.continue

19. Etiological Diagnosis Age as a predictor for eteological diagnosis Age as a predictor for eteological diagnosis A- In CAP: A- In CAP:  Neonates: Common:- = Group B B- hemolytic streptococci = Gram negative enteric bacilli such as Escherichia coli and Klepsella pneumoniae = Gram negative enteric bacilli such as Escherichia coli and Klepsella pneumoniae Less frequent: Less frequent: Staph-auras Staph-auras P.aeruginosa P.aeruginosacontinue

20. Etiological Diagnosis Children Past neonatal period  1- 5 month age Chlamydia trachomatis  > 5 years : Atypical (intracellular) micro-organisms as mycoplasma pneumoniae, legonella, chlamydia SPP are the commonest etiological agents.  All ages Frequent S. pneumoniae Infrequent causes as: Infrequent causes as: - H. influenza (vaccine) - H. influenza (vaccine) - S, aureus but it needs special consideration for - S, aureus but it needs special consideration for rapid progression of the disease. rapid progression of the disease. - Group A B hemolytic streptococci are uncommon - Group A B hemolytic streptococci are uncommon cause of pneumonia cause of pneumoniacontinue

21. Etiological Diagnosis In hospital acquired pneumonia In hospital acquired pneumoniaCommon:  Gram negative organism such as: K. pneumonia, Pseudomonas aurugnosia and serrata spaces  Gram positive organisms such as: S. Aureus most frequent leogionella pneumoniae is rare

22. Investigation of Pneumonia Routine Investigation:  X ray  CBC with differential  SaO 2,  Blood culture Specific Investigation:  Bronchoscopy and C.T for unresolved pneumonia  Serology ( IgM, IgE, IgG)  Sputum and pleural evaluation

23. Out Line (1) Definition and Pathophysiolgoy of pneumomnia (2) Does the patient have a pneumonia? (3) What is the microbial etiology? (3) What is the microbial etiology? (4) Where you treat? (4) Where you treat? (5) How to treat? (5) How to treat?

24. Indication for Hospitalization in Pneumonia 1) Patients with tacchypnea, toxic 1) Patients with tacchypnea, toxic appearance, poor feeding, dehyration appearance, poor feeding, dehyration 2) Infant < 2 months of age 2) Infant < 2 months of age 3) Massive para 3) Massive para pneumonic affusion 4) Associated co-morbidty 5) Immundeficiency.

25. Staphylococcal Pneumonia  It is an infrequent cause of pneumonia  Age under one year, it occurs either community acquired following influenza or at nosocomial setting  Characters:- 1) At the onset, chest radiographs may be normal 1) At the onset, chest radiographs may be normal However. S. aureus pneumonia is more However. S. aureus pneumonia is more commonly bronchopneumonia with a patchy commonly bronchopneumonia with a patchy central infiltrate. Usually unilateral central infiltrate. Usually unilateralContinuecontinue

26. Staphylococcal Pneumonia 2) Rapid progression of the disease from Patchy cansolidation to cavity, pneumatocele or Patchy cansolidation to cavity, pneumatocele or tension pneumothorax should raise the possibility of S. aureus pneumonia, when it occurs tension pneumothorax should raise the possibility of S. aureus pneumonia, when it occurs 3) Effusion or empyema Develops in about 90% of patients Develops in about 90% of patients  Spontaneous pneumothorax or pyopneumothorax Occur in about 25-50% of cases Occur in about 25-50% of cases  Pneumatocele Occur in > 50% of cases and may change hourly in number or size in acute phase. Occur in > 50% of cases and may change hourly in number or size in acute phase.continue

27. Staphylococcal Pneumonia This previous radiographic picture of S. aureus pneumonia is not pathognomonic as it occurs with:  Pneumonia caused by: Klebsiella species, other gram negative bacteria group A streptococci and occasionally pneumococci Klebsiella species, other gram negative bacteria group A streptococci and occasionally pneumococci OR it may mimic congenital diaphragmatic hernia. OR it may mimic congenital diaphragmatic hernia. 4 ) Staphylococcal pneumenia It should be suspected in hospitalized infants (particularly those in ICU) who develop parenchymal unexplained opaque shadows. It should be suspected in hospitalized infants (particularly those in ICU) who develop parenchymal unexplained opaque shadows.continue

28. Staphylococcal Pneumonia 5) Species of staphylococci 5) Species of staphylococci A) S. aureus coagulase positive A) S. aureus coagulase positive B) S. albus B) S. albus C) Staphylococcus epidermidis → coagulase C) Staphylococcus epidermidis → coagulase negative negative  Morphologically all staphylococci are gram positive  Coagulase does not reflect virulence  Virulence of S. aureus related to secretion of different toxins as hemolysins and leukocidin that kills neutrophils.

29. Treatment of Staphylococcal pneumonia The production of B- lactamase by nearly all S. aureus isolates rendered ineffective any drug bydrolysed by this enzyme. The production of B- lactamase by nearly all S. aureus isolates rendered ineffective any drug bydrolysed by this enzyme.  First – line therapy is: Hospital admission, B lactamase resistant penicillin B lactamase resistant penicillin such as Methicillin → no longer in use such as Methicillin → no longer in use its modern analogs i.e oxacillin, cloxacillin, Flucloxacillin, nafcillin its modern analogs i.e oxacillin, cloxacillin, Flucloxacillin, nafcillin  MRSA ( methicillin resistant S. aureus) which was found to be resistant to all B lactams and all cephalosporin compounds.

30. Treatment of Staphylococcal Pneumonia  MRSA infections: that are nosocomially acquired was found to be sensitive to Vancomycin  Now MRSA infection became community acquired  Clindamycin: indicated in MRSA infection in patients allergic to B-lactams  Duration of treatment: 2-3 weeks, but 6 weeks recommended to decrease the risk of relapse  Supportive therapy: o 2, maintenance of, fluid, electrolyte and hemoglobin levels continuecontinue

31. Treatment of Staphylococcal Pneumonia  The most important complication is Empyema and lung abscess, pneumothorax each Empyema and lung abscess, pneumothorax each has a special treatment has a special treatment Treatment in summary  B. lactamase – resistant penicillins or first generation cephalosporin for 2-3 weeks  MRSA → vancomycin  Clindamycin MRSA patient allergic to B lactams patient allergic to B lactams

32. HaemophilusInfluenzaType b   H. influenza is gram - negative bacilli   H. influenza : can lead to invasive infectious in pediatrics as pneumonia, meningitis, cellulites, epiglottites, septic arthritis, osteomyelitis percarditis and bacteremia   Incidance of H. influenza pneumonia decrease after administration of Hib canjugate vaccine   The virulence of serotype b is related to serotype b capsular polysaccharide

33. Haemophilus Influenza Type b  Radiographic findings of H. influenza pneumonia vary from:- 1) Bronchiolctic type with central linear 1) Bronchiolctic type with central linear infiltrates and over inflation infiltrates and over inflation 2)Bronchopneumonia with patchy 2)Bronchopneumonia with patchy consolidation with no lobar affection consolidation with no lobar affection

34. Treatment of H. Influenza Pneumonia we have two clinical situations: 1) pneumonia complicated with bacteremia, 1) pneumonia complicated with bacteremia, pleural effusion usually occur in children less pleural effusion usually occur in children less than 12 months. Those group needs Hospital than 12 months. Those group needs Hospital admission with I.V treatment for 7-10 days admission with I.V treatment for 7-10 dayscontinue

35. Treatment of H. Influenza Pneumonia 2) Pneumonia and the patient is not appears severely ill those group treated at home with oral antimicrobial  Oral therapy in mild H. influenza infection TMP/ SMX or amoxicillin / clavulanate Erythromycin has poor activity  Invasive infections: IV treatment by cephalosporin (cefotaxime or ceftriaxone) Alternatively chloramphencol with ampicillin,

36. Mycoplasma Pneumonia  Mycoplasma pneumoniae causes:  Non classic bacterial pneumonias. They are small organisms that are able to live outside the host cell. Because they have no cell wall, they are not killed by cell wall- active agents such as penicillins and cephalosporins.  Mycoplasma pneumonia is common cause of CAP that occurs > 5 years of age of CAP that occurs > 5 years of age

37. Pathogenesis of Pulmonary Infections Infection with M. pneumoniae are acquired via respiratory route from droplet infection. The organism attaches to a receptor on respiratory epithelium and remains extra cellular causing cellular damage. Specific cell mediated immune responses increase with age so it tends to be milder in children than in adults and also severe in reinfection.

38. Diagnosis of Mycoplasma Pneumonia The diagnostic clue: Is the poor correlation between clinical symptoms which are severe, with minimal pulmonary physical and radiological findings. This poor correlation present all through the course of the disease and this is the hall mark of diagnosis of M.pneumonia.

39. Clinical Picture 1. Typically the patients present with gradual onset of malaise, headache and fever over 1 week. Cough dry or productive associated with symptoms as vomiting, diarrhea, chest pain, sore throat. 2. Physical findings are relatively minimal early in the course of illness no finding on chest examination later on bronchial breathing crackles or wheezes can be heard. 3- Radiologic findings: 3- Radiologic findings:  Usually unilateral in 87% and involves lower lobes  In the early stages the pattern is reticular and interstitial  Later patchy or segmental areas of consolidation are noted. noted.Continue

40. Clinical Picture 4- Extra pulmonary manifestation:  They are the second hallmark of M. pneumonia.  Such complications commonly occur 1-21 days after the onset of respiratory symptoms. Most of the diagnosis have been based on the result of serology (four fold rise in complement fixation titres) rather than no culture confirmation.  Neurological manifestations.  Dermatologic manifestations.  Cardiac manifestations. continue

41. Clinical Picture 4- Extra pulmonary manifestation:  GIT manifestations.  Hematologic manifestations.  Musculoskeletal manifestations.  Genitourinary manifestations.  Immunologic manifestations.

42. Diagnostic Criteria of Mycoplasma Infection Diagnostic Criteria of Mycoplasma Infection Serologic assays are the mainstay for diagnosing mycoplasma infection:- 1.Cold agglutinin identification Cold agglutinins usually appear by the end of first week and disappear by 2-3 months Cold agglutinin responses are non specific and consistent mostly IgM So IgM lacks specificity and sensitivity continue

43. Diagnostic Criteria of Mycoplasma Infection Specific serological test:-  Complement fixation test has been used as standared for diagnosis with titer > 1:32 standared for diagnosis with titer > 1:32  The test measures IgM antibodies  This test has 90% sensitivity and 94% specificity specificity Polymerase chain Reaction(PCR) PCR diagnosis M. pneumonia in both throat swab and CSF. PCR diagnosis M. pneumonia in both throat swab and CSF.

44. Treatment of M. Pneumonia  Macrolides are the drug of choice as:- Erythromycins, Azithromycin are specific treatment.  Because M. pneumonia has no cell wall, it is resistant to penicillins, cephalosporins and resistant to penicillins, cephalosporins and other cell wall active agents. other cell wall active agents.

45. Pneumococcal Pneumonia Pneumococcus (Streptococcus Pneumoniae) It is the most common cause of bacterial pneumonia in children. The organism is gram positive cocci.The virulence of the pneumococci is related to there capsule. It affects all ages. Continue

46. Pneumococcal Pneumonia Pneumococcal PneumoniaDiagnosis: 1)It is typical pneumonia with sudden onset of fever, cough, chest pain and dyspnea. 2)Physical examination: Pleurtic chest pain my be referred to abdomen with misleading suspicion of acute appendicitis. Pleurtic chest pain my be referred to abdomen with misleading suspicion of acute appendicitis. Symptoms and signs of meningismus may be present with upper lobe pneumonia. Symptoms and signs of meningismus may be present with upper lobe pneumonia.Continue

47. Pneumococcal Pneumonia 2) Physical examination: Dullness on percussion denotes empyema because the Dullness on percussion denotes empyema because the lesion usually patchy in distribution lesion usually patchy in distribution Fine rales difficult to be heard. Fine rales difficult to be heard.

48. Pneumococcal Pneumonia Treatment: 1) 1)Penicillins are the drugs of choice in treatment of pneumococcal infection. 2) 2)If the patient is resistant to penicillins, cephalosporin is indicated. 3) 3)If the patient is allergic to penicillins: vancomycin clindamycin or chloramphenecol are the drugs of choice.

49. Recurrent or Unresolved Pneumonia I- Multiple lobe affection: - -Congential heart disease with excess pulmonary blood flow. - - Immune deficiency either local or general. - - Specific infection as T.B and fungal infection (Aspergillus) II- Singal lobe affection: - -Obstruction : Intraluminal, Extraluminal. - - Structural abnormalities as pulmonary sequestration.

50. Differential Diagnosis of Pneumonias 1) Between 4 common types of pneumonia: 1) Between 4 common types of pneumonia:  Staph pneumonia  Mycoplasma Pneumonia  H. influenza pneumonia  Pneumococcal pneumonia 2) From other causes of: 2) From other causes of:  Respiratory distress  Pulmonory inflitrates.