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    1. PNEUMONIA 1

    2. Definition: Pneumonia is an infection of the pulmonary parenchyma. Despite being the cause of significant morbidity and mortality, pneumonia is often misdiagnosed, mistreated, and underestimated. It is usually caused by bacteria. Clinically it presents as an acute illness characterized in the majority of cases by the presence of cough, purulent sputum and fever together with physical signs or radiological changes compatible with consolidation of the lung. 2

    3. Classification : Pneumonia can be classified both anatomically and on the basis of the aetiology. Anatomical classification : Pneumonias are either localized, with the whole of one or more lobes affected (lober pneumonia) , or diffuse, when they primarily affect the lobules of the lung, often in association with the bronchi and bronchioles - a condition referred to as 'bronchopneumonia'. 3

    4. Aetiological classification : An aetiological factor can be discovered in approximately 75% of patients. The term 'atypical pneumonia' has been used to describe pneumonia caused by agents such as Mycoplasma, Legionella, Chlamydia and Coxiella burnetii. While these pneumonias can differ from pneumococcal disease, there is a considerable overlap in clinical presentation and as these agents account for almost one-fifth of the cases of pneumonia , the term 'atypical' has been dropped. 4

    5. Pneumonias may also result from: chemical causes, such as in the aspiration of vomitus radiotherapy allergic mechanisms. Precipitating factors : Strep. pneumoniae - often follows viral infection with influenza or parainfluenza. 5

    6. Hospitalized 'ill' patients - often infected with Gram-negative organisms. Cigarette smoking (the strongest independent risk factor for invasive pneumococcal disease). Alcohol excess. Bronchiectasis (e.g. in cystic fibrosis). 6

    7. Bronchial obstruction (e.g. carcinoma) - occasionally associated with infection with 'non-pathogenic' organisms. Immunosuppression (e.g. AIDS or treatment with cytotoxic agents) - organisms include Pneumocystis carinii, Mycobacterium avium-intracellulare, cytomegalovirus. Intravenous drug abuse - frequently associated with Staph. aureus infection. Inhalation from oesophageal obstruction - often associated with infection with anaerobes. 7

    8. Pathology: Classic pneumonia evolves through a series of pathologic changes. The initial phase is one of edema, with the presence of a proteinaceous exudateand often of bacteriain the alveoli. This phase so rapidly followed by Red hepatization phase. The presence of erythrocytes in the cellular intraalveolar exudate gives this second stage its name, but neutrophils are also present and are important from the standpoint of host defense. Bacteria are occasionally seen in cultures of alveolar specimens collected during this phase. 8

    9. Gray hepatization, no new erythrocytes are extravasating, and those already present have been lysed and degraded. The neutrophil is the predominant cell, fibrin deposition is abundant, and bacteria have disappeared. This phase corresponds with successful elimination of the infection and improvement in gas exchange. 9

    10. Resolution, the macrophage is the dominant cell type in the alveolar space, and the debris of neutrophils, bacteria, and fibrin has been cleared, as has the inflammatory response. This pattern has been described best for pneumococcal pneumonia and may not apply to pneumonias of all etiologies. 10

    11. Clinical features: The clinical presentation varies according to the immune state of the patient and the infecting agent. In the most common type of pneumonia - caused by Strep. pneumoniae - there is often a preceding history of a viral infection. Symptoms: The patient rapidly becomes ill with a high fever pleuritic pain Dry cough. A day or two later, rusty-coloured sputum is produced and at about the same time the patient may develop labial herpes simplex. 11

    12. Signs: high temperature (up to 39.5C) Rapid and shallow breathing the affected side of the chest moves less, and signs of consolidation may be present together with a pleural rub. Investigations : Chest radiography Plain, X-ray - confirms the area of consolidation but radiological changes lag behind the clinical course so that X-ray changes may be minimal at the start of the illness. Conversely, consolidation may remain on the chest X-ray for several weeks after the patient is clinically cured. 12

    13. The chest X-ray usually returns to normal by 6 weeks, except in patients with severe airflow limitation. Persistent changes on the chest X-ray after this time suggest a bronchial abnormality, usually a carcinoma, with persisting secondary pneumonia. Chest X-rays should rarely be repeated more frequently than at weekly intervals during the acute illness and then at 6 weeks after discharge from hospital. CT,chest may be needed . 13

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    18. Gram's Stain and Culture of Sputum : The main purpose of the sputum Gram's stain is to ensure that a sample is suitable for culture. However, Gram's staining may also help to identify certain pathogens (e.g., S. pneumoniae, S. aureus, and gram-negative bacteria) by their characteristic appearance. The sensitivity and specificity of the sputum Gram's stain and culture are highly variable; even in cases of proven bacteremic pneumococcal pneumonia, the yield of positive cultures from sputum samples is 50%. 18

    19. Blood Culture in the presence of bacteramia . Antigen Tests Two commercially available tests detect pneumococcal and certain Legionella antigens in urine. Polymerase Chain Reaction Polymerase chain reaction (PCR) tests are available for a number of pathogens. However, the use of these PCR assays is generally limited to research studies. 19

    20. Serology A fourfold rise in specific IgM antibody titer between acute- and convalescent-phase serum samples is generally considered diagnostic of infection with the pathogen in question, such as Coxiella burnetii. Recently, however, they have fallen out of favor because of the time required to obtain a final result for the convalescent-phase sample. 20

    21. TYPES OF PNEUMONIA Mycoplasma pneumonia: Mycoplasma pneumonia is relatively common and often occurs in patients in their teens and twenties. Generalized features such as headaches and malaise often precede the chest symptoms by 1-5 days. Cough may not be obvious initially and physical signs in the chest may be scanty. On chest X-ray, usually only one lobe is involved but sometimes there may be dramatic shadowing in both lungs. There is frequently no correlation between the X-ray appearances and the clinical state of the patient. 21

    22. The white blood cell count is not raised. Cold agglutinins occur in half of the cases. The diagnosis is confirmed by a rising antibody titre. Treatment is with macrolides, e.g. erythromycin 500 mg four times daily for 7-10 days. Tetracycline is also effective. Although most patients recover in 10-14 days, the disease can be protracted for weeks and relapses occurring. Lung abscesses and pleural effusions are rare. 22

    23. Viral pneumonia Primary viral pneumonia is uncommon in adults, influenza A virus or adenovirus infection being the commonest causes. It predisposes patients to bacterial pneumonia by damaging the respiratory epithelium and facilitating bacterial infection. Influenza A (HSNI) normally does not affect humans but recently has been transmitted from fowls (Avian flu), crossing the species barrier. Patients present with fever, breathlessness, cough and diarrhoea. Lymphopenia and thrombocytopenia are present and pulmonary infiltrates are seen on chest X-ray. The mortality rate is high. 23

    24. Severe acute respiratory syndrome (SARS) is due to a novel coronavirus. The incubation period is approximately 5 days with spread between humans mainly by droplet infection. The outbreak in 2003 affected many healthcare workers. Fever, malaise, headache and rigors were followed in the second week by cough, breathlessness and diarrhoea. Lymphopenia, thrombocytopenia and pulmonary infiltrates (mainly in the lower zones) occur. At the end of the second week 20% of patients deteriorate, developing ARDS, and the mortality is high. 24

    25. Haemophilus influenzae H. influenzae is a frequent cause of exacerbation of chronic bronchitis and can cause pneumonia in COPD patients. The pneumonia can be diffuse or confined to one lobe. There are no special features to separate it from other bacterial pneumonias. It responds well to treatment with oral amoxicillin 500 mg 4 daily. Staphylococcus aureus Staph. aureus rarely cause pneumonia except after a preceding influenzal viral illness. The infection starts in the bronchi, leading to patchy areas of consolidation in one or more lobes, which break down to form abscesses. 25

    26. These may appear as cysts on the chest X-ray. Pneumothorax, effusion and empyemas are frequent. Septicaemia develops with metastatic abscesses in other organs. Fulminating staphylococcal pneumonia can lead to death in hours. Areas of pneumonia (septic infarcts) are also seen in staphylococcal septicaemia. This is frequently seen in intravenous drug abusers. Pulmonary symptoms are often few but breathlessness and cough occur and the chest X-ray reveals areas of consolidation. Abscess formation is frequent. 26

    27. Gram-negative bacteria These are the cause of many hospital-acquired pneumonias but they are occasionally responsible for cases in the community. Klebsiella pneumoniae: Pneumonia due to Klebsiella usually occurs in elderly people with a history of heart or lung disease, diabetes, alcohol excess or malignancy. The onset is often sudden, with severe systemic upset. The sputum is purulent, gelatinous or blood-stained. The upper lobes are more commonly affected and the consolidation is often extensive. . The organism can be found in the sputum or in the blood. Treatment is dependent on the sensitivity of the organism, but a cephalosporin is usually required. The mortality is high, partly owing to the presence of the predisposing condition. 27

    28. Pseudomonas aeruginosa Pneumonia due to Pseudomonas is of considerable significance in patients with cystic fibrosis, since it correlates with a worsening clinical condition and mortality. It is also seen in patients with neutropenia following cytotoxic chemotherapy. The isolation of P. aeruginosa from sputum must be interpreted with care because may simply represent contamination from the upper airways. Treatment with the 4-quinolone antibiotic ciprofloxacin (200-400 mg i.v. over 30-60 minutes twice daily) or ceftazidime (2 g bolus i.v. 8-hourly). Ticarcillin (15-20 g daily i.v. infusion) and piperacillin are active against these bacilli. These penicillins are usually given in combination with an aminoglycoside, e.g. gentamicin, for maximum benefit. 28

    29. GENERAL MANAGEMENT OF PNEUMONIA: Sputum and blood should always be sent for culture but antibiotic treatment should not be delayed. Severe cases need to be admitted to hospital and a chest X-ray performed. Other investigations, e.g. blood gases, are useful to detect respiratory failure and provide a baseline for comparison if the patient deteriorates. The choice of antibiotics is inevitably empirical, and is largely directed at Strep. pneumoniae infections. There is no convincing evidence that newer antibiotics provide any significant therapeutic advantage over established therapies. For treatment of mild community-acquired pneumonia, oral amoxicillin at a dose of at least 500 mg 8-hourly. Oral erythromycin (or clarithromycin, which is better tolerated) is an alternative choice for those sensitive to penicillin. 29

    30. For more severe cases treated in hospital, combined therapy with amoxicillin and a macrolide (erythromycin or clarithromycin) is recommended. When oral therapy is contraindicated, parenteral ampicillin or benzylpenicillin should be combined with clarithromycin. ForStaph. aureus infection intravenous flucloxacillin sodium fusidate should be added. Fluoroquinolones are recommended for those intolerant of penicillins or macrolides. For severe cases, parenteral antibiotics should be given with the combination of a broad-spectrum lactamase-stable beta-lactam antibiotic (co-amoxiclav or cefuroxime) and clarithromycin. 30

    31. Parenteral antibiotics should be switched to oral once the temperature has settled for a period of 24 hours and provided there is no contraindication to oral therapy. The choice of antibiotics may be narrowed once microbiological results are available but it should be remembered that up to 10% of pneumonias may have mixed infections. . 31

    32. Criteria for the diagnosis of severe community-acquired pneumonia: Clinical features Respiratory rate = 30/min Diastolic blood pressure = 60 mmHg Confusion High mortality particularly in those > 65 years old Co-morbidity 32

    33. Investigations Chest X-ray - more than one lobe involved Pao2 < 8 kPa Low albumin (< 35 g/L) White cell count (low < 109/L or high > 20 109/L) Raised serum urea (> 7 mmol/L) Blood culture - positive 33

    34. For more severe cases treated in hospital in addition to antibiotic therapy fluids should be given to avoid dehydration, care of the mouth and skin. Cough should normally be encouraged, but if it is unproductive and distressing, cough suppressants can be given. Physiotherapy is needed to help and encourage the patient to cough. Pleuritic pain may require analgesia, but powerful analgesia (e.g. opiates) should be used with care because they cause respiratory depression. severe hypoxia, oxygen therapy should be given. 34

    35. COMPLICATIONS OF PNEUMONIA Lung abscess This term is used to describe severe localized suppuration in the lung associated with cavity formation on the chest X-ray, often with the presence of a fluid level. Abscesses may develop during the course of specific pneumonias, particularly when the infecting agent is Staph. aureus or Klebsiella pneumoniae. Septic emboli, usually staphylococci, result in multiple lung abscesses. Infarcted areas of lung occasionally cavitate and rarely become infected. Amoebic abscesses may occasionally develop in the right lower lobe following transdiaphragmatic spread from an amoebic liver abscess. The patient is often anaemic with a high ESR. 35

    36. Empyema: Empyema means the presence of pus within the pleural cavity. This usually arises from bacterial spread from a severe pneumonia or after the rupture of a lung abscess into the pleural space. Typically an empyema cavity becomes infected with anaerobic organisms and the patient is severely ill with a high fever and a neutrophil granulocytosis. Empyemas should be treated by prompt tube drainage or by rib resection and drainage of the empyema cavity under ultrasound control. 36