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  1. 1. Respiratory Tract Infections Professor Mark Pallen Dr Kamran Afzal Classified Microbiologist
  2. 2. Throat/Nasal Swab specimens <ul><li>Taken under direct visualization with good lighting </li></ul><ul><li>Areas of exudation, membrane formation or inflammation are choice sites, otherwise rub the tonsillar crypts </li></ul><ul><li>For Bordetella pertussis , collect nasopharyngeal or per nasal swab </li></ul><ul><ul><li>Inform lab in advance to prepare fresh culture media for this organism </li></ul></ul>
  3. 3. <ul><li>For viral agents, instruct patient to gargle with nutrient broth </li></ul><ul><li>For M. leprae , nasal swab or nasal washing is used </li></ul><ul><li>TRANSPORTATION </li></ul><ul><li>Streptococcal pharyngitis or Diphtheria </li></ul><ul><ul><li>Stuart tpt medium, silica gel </li></ul></ul><ul><li>Whooping cough </li></ul><ul><ul><li>Bordetella tpt medium </li></ul></ul><ul><li>Viral infection </li></ul><ul><ul><li>VTM, but if delay, keep at -70 0 C </li></ul></ul>
  4. 4. Collection of Sputum specimens <ul><li>Specimen obtained before start of antibiotic therapy </li></ul><ul><li>If started, inform lab about antibiotics </li></ul><ul><li>Instruct patient appropriately </li></ul><ul><li>Proper labeling </li></ul><ul><li>Patient’s name, test type, date, clinical info </li></ul><ul><li>Preferably collect in working hours </li></ul><ul><li>Collect specimen as early as possible in acute phase, these agents tend to disappear rapidly after the onset of symptoms </li></ul><ul><li>All specimens for viral culture to be frozen and stored at -70 o C </li></ul>
  5. 5. <ul><li>Give the patient a dry, wide mouthed, leak proof container </li></ul><ul><li>Collect sufficient quantity, sterile container </li></ul><ul><li>Early morning specimen is preferred </li></ul><ul><li>Patient should cough deeply to produce a sputum specimen </li></ul><ul><li>For MTB culture, collect 3 x fresh, early morning specimens, keep in a refrigerator to be pooled or processed individually </li></ul><ul><li>In un-cooperative patients, MTB may be recovered from gastric aspiration in the ward </li></ul>
  6. 6. Respiratory tract defences <ul><li>Ventilatory flow </li></ul><ul><li>Cough </li></ul><ul><li>Mucociliary clearance mechanisms </li></ul><ul><li>Mucosal immune system </li></ul>
  7. 7. Predisposing factors for RTIs <ul><li>Low immunity </li></ul><ul><li>Environmental pollution </li></ul><ul><li>Smoking </li></ul><ul><li>Bad nutrition </li></ul><ul><li>Tumors </li></ul><ul><li>Alcohol </li></ul><ul><li>Decreased cough reflex </li></ul><ul><li>Injury to cilia </li></ul><ul><li>Decreased function of alveolar macrophages </li></ul><ul><li>Edema or congestion </li></ul><ul><li>Retention of secretions </li></ul>
  8. 8. Upper respiratory tract infections (URTIs)
  9. 9. 1. Cold and Flu <ul><li>Causative organisms </li></ul><ul><ul><li>Rhino, corona, adeno and parainfluenza viruses </li></ul></ul><ul><ul><li>A novel respiratory pathogen (hMPV) </li></ul></ul><ul><li>Causes respiratory illness in elderly, young children and </li></ul><ul><li>immunocompromised patients </li></ul><ul><li>Symptoms </li></ul><ul><ul><li>Coryzal symptoms, rhinitis, pharyngitis, laryngitis </li></ul></ul><ul><li>Management </li></ul><ul><ul><li>Symptomatic and consists of rest, adequate hydration, simple analgesics and antipyretics </li></ul></ul><ul><ul><li>Antibacterials are not effective and cause adverse consequences of its overuse in treatment of viral infections </li></ul></ul>
  10. 10. 2. Influenza <ul><li>Causative organisms </li></ul><ul><ul><li>Influenza viruses (A, B and C) </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Severe malaise and myalgia complicated by life-threatening secondary bacterial infections as staphylococcal pneumonia </li></ul></ul><ul><li>Management </li></ul><ul><ul><li>Neuraminidase inhibitors (Zanamivir and oseltamivir) </li></ul></ul>
  11. 11. 3. Sore throat (pharyngitis) <ul><li>Causative organism </li></ul><ul><ul><li>Streptococcus pyogenes </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Ranging from fever and symptoms of common cold to inflammation of pharynx with whitish exudate on the tonsils plus enlarged tender cervical lymph nodes </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Is a must to differentiate between viral or streptococcal infections by taking a throat swab for culture </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Wait for results of culture before starting antibiotics </li></ul></ul><ul><ul><li>Penicillins, cephalosporins and macrolides </li></ul></ul>
  12. 12. 3. Laryngitis <ul><li>Most commonly upper respiratory viruses </li></ul><ul><li>Diphtheria </li></ul><ul><ul><li>C. diphtheriae produces a cytotoxic exotoxin causing tissue necrosis at site of infection with associated acute inflammation </li></ul></ul><ul><ul><li>Membrane may narrow airway and/or slough off (asphyxiation) </li></ul></ul>
  13. 13. 4. Acute epiglottitis <ul><li>H. influenzae type B </li></ul><ul><li>Another cause of acute severe airway compromise in childhood </li></ul>
  14. 14. 5. Otitis media <ul><li>Causative organisms </li></ul><ul><ul><li>Inflammation of middle ear seen most frequently in children under 3 years </li></ul></ul><ul><ul><li>Streptococcus pneumoniae , H. influenzae, Strep. pyogenes </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Ear pain, if the drum perforates, the pain is relieved and a purulent discharge follows </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>It should be effective against the 3 main bacterial pathogens </li></ul></ul><ul><ul><li>Co-amoxiclav or the newer cefixime having high activity against H. influenzae </li></ul></ul>
  15. 15. 6. Acute sinusitis <ul><li>Causative organisms </li></ul><ul><ul><li>Caused by similar organisms as otitis media </li></ul></ul><ul><ul><li>Viral upper respiratory tract infections </li></ul></ul><ul><ul><li>Sometimes associated with dental disease </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Facial pain and tenderness accompanied by headache and purulent nasal discharge </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>As otitis media </li></ul></ul><ul><ul><li>Addition of metronidazole (dental disease) </li></ul></ul>
  16. 16. Lower respiratory tract infections (LRTIs)
  17. 17. 1. Acute bronchitis <ul><li>Acute bronchitis is usually infective </li></ul><ul><li>Chronic bronchitis is a chronic inflammatory condition characterized by thickened, edematous bronchial mucosa with mucus gland hypertrophy and usually caused by smoking </li></ul><ul><li>Symptoms </li></ul><ul><ul><li>Yellow or green sputum (pus cells), wheezing </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Airflow optimization </li></ul></ul><ul><ul><ul><li>Physiotherapy to aid expectoration, oxygen and bronchodilatation </li></ul></ul></ul><ul><ul><li>Antibiotic therapy </li></ul></ul><ul><ul><ul><li>First-line agents: Doxycycline, Amoxicillin </li></ul></ul></ul><ul><ul><ul><li>Second-line agents: Co-amoxiclav, clarithromycin, cefixime </li></ul></ul></ul><ul><ul><ul><li>Others: Moxifloxacin, a quinolone effective against gram +ve and -ve </li></ul></ul></ul>
  18. 18. 2. Bronchiolitis <ul><li>It is characterized by inflammatory changes in the small bronchi and bronchioles but not by consolidation </li></ul><ul><li>It attacks infants in the 1 st year of life (airway narrowing) </li></ul><ul><li>Causative organism </li></ul><ul><ul><li>Respiratory syncytial virus (RSV) </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Fever, coryzal symptoms which progresses to wheezing, respiratory distress and hypoxia </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Viral culture of respiratory secretion or IF </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Supportive: oxygen, adequate hydration and vent. assistance </li></ul></ul><ul><ul><li>Severe cases: Ribavirin </li></ul></ul>
  19. 19. 3. Lung abscess <ul><li>Localized suppurative necrosis </li></ul><ul><li>Organisms commonly cultured </li></ul><ul><ul><li>Staphylococci </li></ul></ul><ul><ul><li>Streptococci </li></ul></ul><ul><ul><li>Gram-negative </li></ul></ul><ul><ul><li>Anaerobes </li></ul></ul><ul><ul><li>Frequent mixed infections </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Aspiration </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>Septic emboli </li></ul></ul><ul><ul><li>Tumors </li></ul></ul><ul><ul><li>Bronchiectasis </li></ul></ul>
  20. 20. 4. Bronchiectasis <ul><li>Dilatation of bronchi and bronchioles secondary to chronic inflammation </li></ul><ul><li>Usually due to fibrous scarring following infection (pneumonia, tuberculosis, cystic fibrosis) </li></ul><ul><li>Dilated airways accumulate purulent secretions </li></ul><ul><li>Associated conditions </li></ul><ul><ul><li>Obstruction </li></ul></ul><ul><ul><li>Cystic fibrosis </li></ul></ul><ul><ul><li>Immotile cilia syndromes </li></ul></ul><ul><ul><li>Necrotizing pneumonia </li></ul></ul>
  21. 21. 5. Pulmonary tuberculosis <ul><li>M. tuberculosis/M.bovis main pathogens in man </li></ul><ul><li>Others cause atypical infection especially in immunocompromised host </li></ul><ul><li>Transmitted through inhalation of infected droplets </li></ul><ul><li>T-cell response causes granulomatous inflammation, tissue necrosis and scarring - Hypersensitivity (type IV) </li></ul><ul><li>Pathogenicity due to ability </li></ul><ul><ul><li>to avoid phagocytosis </li></ul></ul><ul><ul><li>to stimulate a host T-cell response </li></ul></ul>
  22. 22. <ul><ul><li>Pathology </li></ul></ul><ul><ul><ul><li>Cavitary fibrocaseous lesions </li></ul></ul></ul><ul><ul><ul><li>Bronchopneumonia </li></ul></ul></ul><ul><ul><ul><li>Miliary TB </li></ul></ul></ul>Miliary Granuloma Fibrocaseous Mycobacterium
  23. 23. Primary and secondary TB <ul><li>Primary </li></ul><ul><ul><li>The site of infection shows non-specific inflammation with developing granulomas in nodes </li></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>There are primed T cells which stimulate a localised granulomatous response </li></ul></ul>
  24. 24. 6. Pneumonia <ul><li>Pneumonia is defined as inflammation of alveoli and interstitium of the lungs of infective origin and characterized by consolidation </li></ul><ul><ul><li>Alveoli are filled with a mixture of inflammatory exudates, bacteria and WBCs (opaque shadow on chest X-ray) </li></ul></ul><ul><li>It is classified as </li></ul><ul><ul><li>Community-acquired </li></ul></ul><ul><ul><li>Hospital-acquired </li></ul></ul><ul><ul><li>Opportunistic </li></ul></ul>
  25. 25. Microbial Pathogens Causing Pneumonia             Pneumocystis carinii S. pneumoniae H. Influenzae M. tuberculosis Enteric aerobic gram-negative bacilli Staph. aureus Pseudomonas aeruginosa Oral anaerobes Streptococcus pneumoniae Haemophilus influenzae Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophila Moraxella catarrhalis Staphylococcus aureus Nocardia spp. Mycobacterium tuberculosis Chlamydia psittacii Oral anaerobes Viruses Fungi   Opportunistic Hospital-Acquired Community-Acquired
  26. 26. A. Community-acquired pneumonia <ul><li>Causative organisms </li></ul><ul><ul><li>Strep. pneumoniae causes both lobar and bronchopneumonia </li></ul></ul><ul><ul><li>H. influenzae causes bronchopneumonia, also causes secondary bacterial pneumonia on primary viral pneumonia </li></ul></ul><ul><ul><li>L. pneumophila is the cause of Legionnaire’s disease occurring sporadically and in outbreaks associated with contaminated air-conditioning or water systems, rapidly progressive with extensive consolidation and respiratory failure </li></ul></ul><ul><ul><li>Chickenpox is complicated by primary varicella pneumonia </li></ul></ul>
  27. 27. <ul><li>Symptoms </li></ul><ul><ul><li>Pneumococcal lobar pneumonia: Dry cough but later produce purulent or blood-stained, rust-colored sputum, dyspnea, fever, pleuritic chest pain </li></ul></ul><ul><li>Chest X-ray shows consolidation in one or two lobes </li></ul>
  28. 28. B. Hospital-acquired pneumonia <ul><li>Causative organisms </li></ul><ul><ul><li>Gram-negative bacilli, Staph aureus , pneumococcal pneumonia and Legionella infection </li></ul></ul><ul><ul><li>Ventilator-associated pneumonia (VAP) is acquired in ICUs where broad spectrum antibiotics are frequently used and where there is resident flora with an antibiotic resistance pattern </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Nosocomial pneumonia accounts for 10-15% of all hospital-acquired infections presenting with sepsis and respiratory failure </li></ul></ul><ul><ul><li>Predisposing features: stroke, mechanical ventilation, chronic lung disease, recent surgery and broad spectrum antibiotic exposure </li></ul></ul>
  29. 29. Aspiration pneumonia <ul><li>It can be seen in community or hospital </li></ul><ul><li>Caused by inhalation of stomach contents contaminated by bacteria from the mouth (when the patient vomits while unconscious) </li></ul><ul><ul><li>Anaerobic bacteria are implicated often accompanied by aerobic organisms </li></ul></ul><ul><li>Gastric acid is very destructive to lung tissue causing severe tissue necrosis and infection with abscess </li></ul><ul><li>Risk factors </li></ul><ul><ul><li>Alcohol, hypnotic drugs and GA </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Metronidazole plus amoxicillin or metronidazole plus cefotaxime if you suspect gram-negative infection </li></ul></ul>
  30. 30. C. Opportunistic pneumonias <ul><li>Infections that affect immunosuppressed patients </li></ul><ul><li>Associated disorders </li></ul><ul><ul><li>AIDS </li></ul></ul><ul><ul><li>Cancer patients </li></ul></ul><ul><ul><li>Transplant recipients </li></ul></ul>Pneumocystis carinii Aspergillus Cytomegalovirus
  32. 32. <ul><li>LOBAR PNEUMONIA </li></ul><ul><ul><li>Involvement of the entire lung lobe </li></ul></ul><ul><li>BRONCHOPNEUMONIA </li></ul><ul><ul><li>Patchy consolidation in 1 or several lobes, usually in dependent lower or posterior portions centered around bronchi and bronchioles </li></ul></ul><ul><li>INTERSTITIAL PNEUMONIA </li></ul><ul><ul><li>Inflammation of the interstitium, including the alveolar walls and connective tissue around the bronchovascular tree </li></ul></ul><ul><li>MILIARY PNEUMONIA </li></ul><ul><ul><li>Numerous discrete lesions due to hematogenous spread </li></ul></ul>
  33. 33. A. Lobar Pneumonia <ul><li>Confluent consolidation involving a complete lung lobe </li></ul><ul><li>Most often due to Streptococcus pneumoniae </li></ul><ul><li>Can be seen with other organisms ( Klebsiella, Legionella ) </li></ul>
  34. 34. Pathology <ul><li>Lung </li></ul><ul><ul><li>Congestion </li></ul></ul><ul><ul><li>Red hepatisation </li></ul></ul><ul><ul><li>Grey hepatisation </li></ul></ul><ul><ul><li>Resolution </li></ul></ul><ul><li>A classical acute inflammatory response </li></ul><ul><ul><li>Exudation of fibrin-rich fluid </li></ul></ul><ul><ul><li>Neutrophil infiltration </li></ul></ul><ul><ul><li>Macrophage infiltration </li></ul></ul><ul><ul><li>Resolution </li></ul></ul><ul><li>Immune system plays a part </li></ul><ul><ul><li>Antibodies lead to opsonisation, phagocytosis of bacteria </li></ul></ul>
  35. 35. <ul><li>Pathogenesis </li></ul><ul><ul><li>Inhalation of air droplets </li></ul></ul><ul><ul><li>Aspiration of infected secretions or objects </li></ul></ul><ul><ul><li>Hematogenous spread </li></ul></ul>
  36. 36. B. Bronchopneumonia <ul><li>The consolidation is patchy and not confined by lobar architecture </li></ul><ul><li>Infection starts in airways and spreads to adjacent alveolar lung </li></ul><ul><li>More varied microbiology </li></ul><ul><ul><li>Strep. pneumoniae, Haemophilus influenzae, Staphylococcus , anaerobes, coliforms </li></ul></ul><ul><li>Clinical context may help </li></ul><ul><ul><li>Staph/anaerobes/coliforms seen in aspiration </li></ul></ul>
  37. 37. Viral pneumonia <ul><li>Gives a pattern of acute injury similar to adult respiratory distress syndrome (ARDS) </li></ul><ul><li>Acute inflammatory infiltration less obvious </li></ul><ul><li>Viral inclusions sometimes seen in epithelial cells </li></ul>
  38. 38. C. Atypical Pneumonia <ul><li>Atypical pneumonia is caused by atypical bacteria that do not stain with Gram stain or do not fit in any category like in virus or bacteria </li></ul><ul><li>The inflammation is confined to interstitial spaces between alveoli </li></ul><ul><li>Radiologically gives appearance of reticulo-nodular pattern </li></ul><ul><ul><li>Linear thread like opacities in lungs </li></ul></ul>
  39. 39. Comparison Not prominent Prominent (myalgia, fatigue, N/V, diarrhea) Extra-pulmonary symptoms Purulent Scanty Sputum Productive cough Dry cough Cough Abrupt Gradual Onset S. pneumoniae , H. influenzae , K. pneumoniae , mixed aerobic and anaerobic oral flora M. pneumoniae , L. pneumophilia, C. pneumophilla, viruses, protozoa and fungi Etiology TYPICAL PNEUMONIA ATYPICAL PNEUMONIA
  40. 40. Investigations <ul><li>Microscopy is unreliable due to oropharyngeal contamination </li></ul><ul><li>Gram stain </li></ul><ul><li>ZN stain for AFB </li></ul><ul><li>Sputum culture is the mainstay of diagnosis for pneumonia caused by pneumococci and H. influenzae </li></ul><ul><li>Total and differential blood count </li></ul><ul><li>Blood, urine, sputum -> Culture/sensitivity </li></ul><ul><li>Serological investigations </li></ul><ul><li>Antigen detection in sputum or urine by </li></ul><ul><ul><li>Fluorescent methods, Immunoelectrophoresis, Latex agglutination, ELISA </li></ul></ul>
  41. 41. <ul><li>Fibreoptic bronchoscopy with bronchial washing/ brushing /biopsy -> Histopathology (more sensitive but more invasive) </li></ul><ul><li>Molecular techniques </li></ul><ul><li>Radiology -> CXR, MRI and CT scan </li></ul><ul><li>Serology </li></ul><ul><li>By serological methods using acute and convalescent sera </li></ul><ul><li>Significantly raised titer or rising titer of antibodies give clues to diagnosis </li></ul>
  42. 42. <ul><li>Specific Serological Tests </li></ul><ul><li>Legionella pneumophila </li></ul><ul><ul><li>Rapid microagglutination test </li></ul></ul><ul><ul><li>Test for Legionella antigen in the urine </li></ul></ul><ul><li>Mycoplasma pneumoniae </li></ul><ul><ul><li>Complement fixation test </li></ul></ul><ul><ul><li>IgM by latex agglutination or ELISA </li></ul></ul><ul><ul><li>Cold agglutinin test </li></ul></ul>
  43. 43. <ul><li>Chlamydia </li></ul><ul><ul><li>Microimmunofluorescence </li></ul></ul><ul><ul><li>ELISA </li></ul></ul><ul><li>Coxiella burnetii </li></ul><ul><ul><li>Complement fixation test </li></ul></ul><ul><li>Serologic tests </li></ul><ul><ul><li>A four fold or greater rise in titer is confirmatory of an acute infection </li></ul></ul>
  44. 44. Treatment <ul><li>Targeted treatment </li></ul><ul><li>Pneumococcal pneumonia </li></ul><ul><ul><li>Benzyl penicillin or Amoxicillin </li></ul></ul><ul><ul><li>Erythromycin (in penicillin-allergic patients) </li></ul></ul><ul><ul><li>Combined β - lactam + macrolide </li></ul></ul><ul><ul><ul><li>when pneumonia is complicated by pneumococcal bacteremia </li></ul></ul></ul><ul><li>H. influenzae </li></ul><ul><ul><li>Co-amoxiclav, parenteral cefuroxime, cefixime </li></ul></ul><ul><ul><li>Clarithromycin and azithromycin </li></ul></ul>
  45. 45. <ul><li>Morexella pneumonia </li></ul><ul><ul><li>Doesn’t possess cell wall so not susceptible to β -lactams </li></ul></ul><ul><ul><li>Tetracyclins and quinolones </li></ul></ul><ul><li>Staphylococcal pneumonia </li></ul><ul><ul><li>Flucloxacillin + a second agent as rifampicin, fusidic acid or gentamycin </li></ul></ul><ul><li>Legionnaire’s disease </li></ul><ul><ul><li>Erythromycin or azithromycin </li></ul></ul>
  46. 51. LAW OF CONSERVATION OF KNOWLEDGE <ul><li>“ No matter how long the lecture may be, </li></ul><ul><li>the knowledge before and after the lecture remains constant” </li></ul>