PNEUMONIA. Pneumonia is an inflammation of the lungs caused by bacteria, viruses, fungi, rickettsiae and other microorganisms.

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1 PNEUMONIA Dr. A.Torossian, M.D., Ph. D. Department of Respiratory Diseases Definition Pneumonia is an inflammation of the lungs caused by bacteria, viruses, fungi, rickettsiae and other microorganisms. Sometimes they may also be due to the inhalation of chemicals or trauma to the chest wall. 1

2 Classifications Based on various characteristics of the illness, such as: Anatomic or radiologic distribution Lobar pneumonia Segmental pneumonia Bronchopneumonia (multifocal or lobular pneumonia) Interstitial pneumonia The pathogen responsible The setting or mechanism of acquisition Setting of Infection Community-acquired pneumonia Community-acquired pneumonia (CAP) is defined as pneumonia that develops in the outpatient setting or within 48 hours of admission to a hospital. 2

3 Hospital-acquired pneumonia (HAP) Pneumonia that develops at least 48 hours after admission to a hospital and is characterized by increased risk of exposure to multidrug-resistant (MDR) organisms,as well as gram-negative organisms. Risk factors for exposure to such organisms in HAP include the following : Antibiotic therapy within 90 days of the hospital-acquired infection Current length of hospitalization of 5 days or more High frequency of antibiotic resistance in the local community or within the specific hospital unit Immunosuppressive disease or therapy Healthcare-associated pneumonia Nursing home-associated pneumonia Ventilator-associated pneumonia Nursing home patients with pneumonia are less likely to present with classic signs and symptoms of the typical pneumonia presentation, such as fever, chills, chest pain, and productive cough, but instead often have delirium and altered mental status. VAP may occur in as many as 10-20% of patients who are on ventilators for more than 48 hours. 3

4 Aspiration Pneumonia Caused by the aspiration of oropharyngeal secretions into the lung Patients with increased risk of aspiration and/or the development of aspiration pneumonia : Decreased ability to clear oropharyngeal secretions - Poor cough or gag reflex, impaired swallowing mechanism (eg. dysphagia in stroke patients), impaired ciliary transport (eg. from smoking) unconsciousness- seizures, coma, anesthesia Increased volume of secretions Increased bacterial burden of secretions Presence of other comorbidities - Anatomic abnormalities, gastroesophageal reflux Intubation/extubation Because the episode of aspiration is usually not witnessed, the diagnosis is inferred when a patient at risk of aspiration develops evidence of a radiographic infiltrate in characteristic anatomic pulmonary locations or bronchopulmonary segments. The classic findings are in the right lower lobe. 4

5 Causes: Community Acquired Pneumonia Bacteria: Typical Streptococcus Pneumoniae Staphylococcus aureus Haemophilus Influenzae Moraxella catarrhalis Hospital-acquired pneumonia Typical :Gram-negative bacteria Pseudomonas aeruginosa Klebsiella pneumoniae Haemophilus influenzae Escherichia coli Acinetobacter baumannii and others 5

6 Atypical organisms Atypical organisms are generally associated with a milder form of pneumonia, the so-called "walking pneumonia." A feature that makes these organisms atypical is the inability to detect them on Gram stain or to cultivate them in standard bacteriologic media. Mycoplasmapneumoniae: Mycoplasmas are the smallest known free-living organisms in existence; they lack cell walls (and therefore are not apparent after Gram stain) but have protective 3-layered cell membranes. Chlamydophila species (Chlamydophila psittaci, Chlamydophila pneumoniae): Psittacosis, also known as parrot disease or parrot fever, is caused by C psittaci and is associated with the handling of various types of birds. Legionella species: Legionella species are gram-negative bacteria found in freshwater; they are known to grow in complex water distribution systems; institutional water contamination is frequently noted in endemic outbreaks. Legionella species are the causative agent of Legionnaires disease. Coxiella burnetii: C burnetii is the causative agent of Q fever. It is spread from animals to humans; person-to-person transmission is unusual. Animal reservoirs typically include cats, sheep, and cattle. Anaerobic organisms Pneumonia due to anaerobes typically results from aspiration of oropharyngeal contents. These infections tend to be polymicrobial and may consist of the following anaerobic species: Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella. They are often combined with aerobic species. 6

7 Viruses Common causes of viral pneumonia are: Influenza virus A and B Respiratory syncytial virus (RSV) Human parainfluenza viruses (in children) Rarer viruses that commonly result in pneumonia include: Adenoviruses (in military recruits) Metapneumovirus Severe acute respiratory syndrome virus (SARS coronavirus) Viruses that primarily cause other diseases, but sometimes cause pneumonia include: Herpes simplex virus (HSV), mainly in newborns Varicella-zoster virus (VZV) Cytomegalovirus (CMV), mainly in people with immune system problems Fungal pneumonia Endemic fungal pathogens (eg, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis) cause infection in both healthy and immunocompromised hosts in defined geographic locations of the Americas and around the world. Opportunistic fungal organisms (eg, Candida species, Aspergillus species, Mucor species, Cryptococcus neoformans) tend to cause pneumonia in patients with congenital or acquired defects in their host defenses. 7

8 Parasitic pneumonia The most common parasites involved: Ascariasis Schistosoma Toxoplasma gondii The most common bacterial pathogens that cause CAP include Streptococcus pneumoniae (both penicillin-sensitive and -resistant strains), H influenzae (both ampicillin-sensitive and -resistant strains), and Moraxella catarrhalis (all strains penicillin-resistant). These 3 pathogens account for approximately 85% of CAP cases. 8

9 Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa are not causes of CAP in typical hosts. S aureus causes CAP in the setting of postviral influenza. K pneumoniae CAP occurs primarily in persons with chronic alcoholism. Ps. aeruginosa is a cause of CAP in patients with bronchiectasis or cystic fibrosis. Other gram-negative pathogens rarely cause CAP. Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most common bacterial causes of HAP HAP can also be caused by viruses, fungi, anaerobic bacteria and combinations of these 9

10 Ethiology of CAP (European region) cause Typical pathogens Streptococcus pneumoniae Haemophillus inflienzae Moraxellacatarrhalis Atypical pathogens Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila Others Viral agents Pneumocystis carinii Mycobacterium tuberculosis Unknown pathogen percentage (%) CAP is usually acquired via inhalation or aspiration of pulmonary pathogenic organisms into a lung segment or lobe. Less commonly, CAP results from secondary bacteremia from a distant source, such as Escherichia coli urinary tract infection CAP due to aspiration of oropharyngeal contents involves multiple pathogens. 10

11 Anamnesis Determining the presence of pneumonia Assessing disease severity at the time of presentation Identifying the causative agent Anamnesis Symptoms The presence of cough, particularly cough productive of sputum, is the most consistent presenting symptom. The character of the sputum may suggest a particular pathogen, for example: Rust-colored sputum - Frequently associated with infection by S. pneumoniae Foul-smelling or bad-tasting sputum - Often produced by anaerobic infections Chest pain, dyspnea, hemoptysis, are also highly indicative of a pulmonary process Nonspecific symptoms such as fever, rigors or shaking chills, and malaise are common. Other nonspecific symptoms - myalgia, arthralgia, headacheoften seen in cases with atypical pneumonia sometimes nausea, vomiting, diarrhea, and altered sensorium. 11

12 Anamnesis Potential exposures Exposure to contaminated air-conditioning or water systems -Legionella species Exposure to overcrowded institutions (eg. jails, homeless shelters) S pneumoniae, Mycoplasma Exposure to various types of animals - cats, cattle, sheep, goats (C burnetii, B anthracis) turkeys, chickens, ducks, or other birds (C psittaci), etc. Anamnesis Patients at increased risk of aspiration are also at increased risk of developing pneumonia secondarily Aspiration risks Alcoholism Altered mental status Anatomic abnormalities, congenital or acquired Dysphagia GERD (gastro-esophageal reflux disease) Seizure disorder,unconsciousness 12

13 Anamnesis Additional host factors Comorbid conditions Previous surgeries Possibility of immunosuppression Social history Family history Medication history Allergy history Risk Factors for severe disease Age over 65 years Recent antibiotics Immune compromised (e.g. HIV Infection) Respiratory illness (COPD, Asthma) Diabetes Mellitus Chronic Liver Disease Chronic Kidney Disease Cancer 13

14 Physical examination Physical examination findings may vary depending on the type of organism, severity of infection, coexisting host factors, and the presence of complications. Signs: Hyperthermia (fever, typically >38 C) or hypothermia (<35 C) Tachypnea (>18 respirations/min) Use of accessory respiratory muscles Tachycardia (>100 bpm) or bradycardia (<60 bpm) Central cyanosis Altered mental status Physical examination Adventitious breath sounds, such as rales/crackles, rhonchi or wheezes Decreased intensity of breath sounds Whispering pectoriloquy Dullness to percussion 14

15 HOW TO DIFFERENTIATE BETWEEN PNEUMONIA AND OTHER RESPIRATORY TRACT INFECTIONS? A patient should be suspected of having pneumonia when the following signs and symptoms are present: an acute cough and one of the following: new focal chest signs, dyspnoea, tachypnoea, fever > 4 days. If pneumonia is suspected, a chest X-ray should be performed to confirm the diagnosis. Imaging methods Chest X-ray Radiology is generally helpful in detecting suspected pneumonia and identifying the presence of complications only occasionally can imaging suggest specific pathogens 15

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17 Computed tomography CT scanning may identify pulmonary infections earlier than plain radiography. In most cases, it can be helpful in the analysis of more complex lung findings and evaluation of other intrathoracic structures. Ultrasonography Ultrasonography is useful in evaluating suspected parapneumonic effusions, especially if septations are present within the fluid collection that may not be visible on CT scans. Ultrasonography also has great utility for direct operation by physicians at the patient bed 17

18 Labs The amount of laboratory and microbiological work-up should be determined by the severity of pneumonia Complete Blood Count Sputum Gram stain Sputum Culture C-reactive protein Consider urine antigen testing for pneumococcus and Legionella pneumophila Tests The following initial tests are indicated in more severe cases: Blood culture, prior to antibiotic therapy Endotracheal aspirate for culture in intubated patients Culture and study of pleural fluid if effusion is present 18

19 Procedures Bronchoscopy with or without bronchoalveolar lavage (BAL): Lung tissue can be visually evaluated and bronchial washing specimens can be obtained with the aid of a fiberoptic bronchoscope. Protected brushings and BAL can be performed for fluid analysis and cultures. Thoracocentesis: This is an essential procedure in patients with a parapneumonic pleural effusion. Obtaining fluid from the pleural space for laboratory analysis allows for the differentiation between simple and complicated effusions. The fluid can also be sent for Gram stain and culture. Treatment Almost all major decisions regarding management of pneumonia address the initial assessment of severity. Perhaps the most important initial determination is that of the need for hospitalization. In determining site or level of care, options include outpatient, medical ward care, or medical ICU care. 19

20 Various systems to assess the severity of disease and risk of death exist and are in wide use, including the PSI/PORT (ie, Pneumonia Severity Index/Patient Outcomes Research Team score), CURB- 65 and others Severity mild moderate severe Place of treatment Out-patient hospital ICU Gr.1 Gr. 2 Gr. 3 Gr. 4 Gr. 5 Ramirez, Dis Manage Heart Outcomes 2003; 11 (1)

21 CURB-65 CURB-65 One point is given for the presence of each of the following: Confusion of new onset - Altered mental status Uremia -BUN greater than 7 mmol/l Respiratory rate -Greater than or equal to 30 breaths per minute Blood pressure -Systolic less than 90 mm Hg or diastolic less than 60 mm Hg Age older than 65 years Thorax 2009;64(Suppl III):iii1 iii55. doi: /thx.2009 BTS guidelines 21

22 WHO SHOULD BE CONSIDERED FOR ICU ADMISSION? Criteria of acute respiratory failure, severe sepsis or septic shock and radiographic extension of infiltrates should prompt consideration of the admission to the ICU or an intermediate care unit. The presence of at least two of systolic blood pressure < 90 mmhg, severe respiratory failure (PaO2/FIO2 < 250), Involvement of > 2 lobes on chest radiograph (multilobar involvement) or one of requirement for mechanical ventilation or requirement of vasopressors > 4 hours (septic shock) indicates severe CAP and can be used to guide ICU referral. Differentiation between communityacquired pneumonia (CAP), healthcareassociated pneumonia (HCAP), hospitalacquired pneumonia (HAP), and other pulmonary pathology at presentation is important for several reasons, but primarily because the varying pathogens implicated in each category dictate the empiric therapy likely to be most useful. 22

23 Management Determine if hospitalization needed Be aware of Antibiotic Resistance Start antibiotic within 4 hours of hospitalization Decreases mortality Decreases length of stay Review of patients in the community with CAP is recommended after 48 h or earlier if clinically indicated. Disease severity assessment should form part of the clinical review. Those who fail to improve after 48 h of treatment should be considered for hospital admission or chest radiography. 23

24 Medication The goals of pharmacotherapy for bacteria pneumonia are to eradicate the infection, reduce morbidity, and prevent complications. Treatment of pneumonia depends largely on the empiric use of antibiotic regimens directed against potential pathogens as determined by the setting in which the infection took place and potential for exposure to multidrug-resistant (MDR) organisms and other more virulent pathogens (ie, CAP, healthcare-acquired pneumonia (HCAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP). Duration of medication Usually 7-10 days Atypical pathogens-min 14 days Clinical improvement is expected during the first 2-3 days The patients should be instructed to contact the physician if there is no improvement 24

25 SETTING LRTI TYPE SEVERITY/SUB-GROUP PREFERRED ALTERNATIVE* COMMUNITY ALL AMOXICILLIN or TETRACYCLINE** CO-AMOXICLAV MACROLIDE*** LEVOFLOXACIN MOXIFLOXACIN HOSPITAL MILD AMOXICILLIN or TETRACYCLINE** CO-AMOXICLAV MACROLIDE*** LEVOFLOXACIN MOXIFLOXACIN COPD MODERATE / SEVERE CO-AMOXICLAV LEVOFLOXACIN MOXIFLOXACIN COPD CAP CAP CAP BRONCHIECT ASIS + RISK FACTORS FOR Ps aeruginosa NON-SEVERE SEVERE SEVERE + RISK FACTORS FOR Ps aeruginosa NO RISK ACTORS FOR Ps aeruginosa CIPROFLOXACIN PENICILLIN G ± MACROLIDE*** AMINOPENICILLIN ± MACROLIDE*** CO-AMOXICLAV ± MACROLIDE*** 2 nd OR 3 rd CEPHALOSPORIN ± MACROLIDE*** 3 rd CEPHALOSPORIN + MACROLIDE*** ANTI-PSEUDOMONAL CEPHALOSPORIN + CIPROFLOXACIN AMOXICILLIN CLAVULANATE MOXIFLOXACIN LEVOFLOXACIN LEVOFLOXACIN MOXIFLOXACIN 3 rd CEPHALOSPORIN + (LEVOFLOXACIN OR MOXIFLOXACIN) ACYLUREIDOPENICILL IN/β-LACTAMASE INHIBITOR + CIPROFLOXACIN or CARBAPENEM + CIPROFLOXACIN Oral therapy with amoxicillin and a macrolide is preferred for patients with moderate severity CAP who require hospital admission. Monotherapy with a macrolide may be suitable for patients who have failed to respond to an adequate course of amoxicillin prior to admission. 25

26 When oral therapy is contraindicated, the preferred parenteral choices include intravenous amoxicillin or benzylpenicillin, together with clarithromycin. For those intolerant of penicillins or macrolides, oral doxycyline is the main alternative agent. Oral levofloxacin and oral moxifloxacin are other alternative choices. Patients with high severity pneumonia should be treated immediately after diagnosis with parenteral antibiotics. An intravenous combination of a broad-spectrum betalactamase stable antibiotic such as co-amoxiclav together with a macrolide such as clarithromycin is preferred. In patients allergic to penicillin, a second-generation (eg, cefuroxime) or third-generation (eg, cefotaxime or ceftriaxone) cephalosporin can be used instead of coamoxiclav, together with clarithromycin. 26

27 Aspiration pneumonia empiric therapy Although the causative organisms in aspiration pneumonia have been noted to be similar to those of CAP or HCAP, patients with severe periodontal disease, putrid sputum, or a history of alcoholism with suspected aspiration pneumonia may be at greater risk of anaerobic infection. One of the following antibiotic regimens is suggested for such patients: Piperacillin-tazobactam Imipenem Clindamycin or metronidazole plus a respiratory fluoroquinolone plus ceftriaxone Additional supportive care measures : Analgesia and antipyretics Intravenous fluids (and, conversely, diuretics) if indicated Oxygen supplementation Respiratory therapy, including treatment with bronchodilators and N acetylcysteine Chest physiotherapy, early mobilization 27

28 Low molecular heparin is indicated in patients with acute respiratory failure. Steroids have no place in the treatment of pneumonia unless septic shock is present Suctioning and bronchial hygiene mechanical ventilation Clinical response to antibiotic therapy should be evaluated within hours of initiation. With appropriate antibiotic therapy, improvement in the clinical manifestations of pneumonia should be observed in hours. Because of the time required for antibiotics to act, antibiotics should not be changed within the first 72 hours unless marked clinical deterioration occurs. 28

29 WHEN SHOULD IV BE USED AND WHEN SHOULD THE SWITCH TO ORAL OCCUR? In mild pneumonia, treatment can be applied orally from the beginning. In patients with moderate pneumonia, sequential treatment should be considered in all patients except the most severely ill. The optimal time to switch to oral treatment is also unknown; it seems reasonable to target this decision according to the resolution of the most prominent clinical features at admission. The timing of radiologic resolution of pneumonia varies with patient age and the presence or absence of an underlying lung disease. The chest radiograph usually clears within 4 weeks in patients younger than 50 years without underlying pulmonary disease. 29

30 If patients do not improve within 72 hours, an organism that is not susceptible or is resistant to the initial empiric antibiotic regimen should be considered. Lack of response may also be secondary to a complication such as empyema or abscess formation. Also consider broadening the differential diagnosis to include noninfectious etiologies such as malignancies, congestive heart failure, etc., or other pathogens - M.Tuberculosis Diagnostic testing may require more complex studies when the cause of disease is less apparent. Further Outpatient Care When treated in an outpatient setting, arranging adequate follow-up evaluations for the patient is mandatory. Patients also should be instructed to return if their condition deteriorates. Patients should have a follow-up chest radiograph to ensure resolution of consolidation. Chest radiograph findings indicating nonresolution should raise the consideration of an endobronchial obstruction as a cause of postobstructive pneumonia. A CT scan may be of benefit in these cases. 30

31 Complications Potential complications include the following: Destruction and fibrosis/organization of lung parenchyma Necrotizing pneumonia/pulmonary abscess Bronchiectasis Empyema Respiratory failure Acute respiratory distress syndrome Death Differential diagnosis Lung cancer Other malignancy Tuberculosis Fibrosis Collagenosis PT others 31

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34 Prognosis Generally, the prognosis is good in otherwise healthy patients with uncomplicated pneumonia Advanced age, aggressive organisms (eg, Klebsiella, Legionella, resistant S.pneumoniae), comorbidity, respiratory failure, neutropenia, and features of sepsis, alone or in combination, increase morbidity and mortality 34