Pneumonia

A presentation during our Medicine Posting (Internship days)

1. A Discussion On The Killer Infectious Disease Of Lungs: Pneumonia Presented By: Dr. Pravin Prasad Dr. Rabin Babu Paudyal Interns, Medicine Unit III

2. PNEUMONIA: INTRODUCTION Pneumonia is an infection of the pulmonary parenchyma. (Harrison- 18 th Ed) Pneumonia is defined as an acute respiratory illness associated with recently developed radiological pulmonary shadowing which may be segmental, lobar or multilobar. (Davidson- 21 st Ed) Pneumonia was typically classified as community-acquired (CAP), hospital-acquired (HAP), or ventilator-associated (VAP). Over the past two decades, however, some persons presenting as outpatients with onset of pneumonia have been found to be infected with the multidrug-resistant (MDR) pathogens previously associated with HAP: - thus development of the term Health Care – associated Pneumonia (HCAP) .

3. MDR Pathogens for Pneumonia: Factors Responsible Factors responsible for this phenomenon include: D evelopment and widespread use of potent oral antibiotics, Earlier transfer of patients out of acute-care hospitals to their homes or various lower-acuity facilities, Increased use of outpatient IV antibiotic therapy, General aging of the population, and More extensive immuno-modulatory therapies. Pneumonia: Introduction

4. Pneumonia: Classification I Classification By Site Lobar Pneumonia Bronchopneumonia Interstitial Pneumonia

5. Pneumonia: Classification II Classification By Aetiology Primary Pneumonia Secondary Pneumonia (including Aspiration Pneumonia) Suppurative Pneumonia (necrotizing pneumonia) Common Organisms Less Common Organisms Streptococcous pneumoniae Klebsiella pneumoniae Haemophilus influenza Streptococcus pneumonia Moraxella catarrhalis Pseudomonas aeruginosa Staphylococcus aureus Coxiella burnetii Legionella pneumophilia Chlamydia pneumoniae Mycoplasma pneumoniae Chlamydia psittaci Actinomyces israeli Viruses (including SARS) Table 1: Organisms responsible for primary pneumonia

6. Pneumonia: Classification III Classification by mode of acquiring pneumonia Community-acquired Pneumonia Hospital acquired pneumonia, or Ventilator associated pneumonia) Health Care Associated Pneumonia Pneumonia in immuno-compromised host

7. Pneumonia: Pathophysiology Pneumonia results from the proliferation of microbial pathogens at the alveolar level and the host's response to those pathogens. Microorganisms gain access to the lower respiratory tract in several ways. Aspiration from the oropharynx; (most common) I nhalation of contaminated droplets; Hematogenous spread Contiguous extension.

8. Pneumonia: Pathophysiology (contd.) Defense Mechanisms against Pneumonia Hairs and turbinates of the nares B ranching architecture of the tracheobronchial tree Muco-ciliary clearance and local antibacterial factors Gag reflex and the cough mechanism the normal flora adhering to mucosal cells of the oropharynx Alveolar Macrophages, local proteins (e.g., surfactant proteins A and D)

9. Pneumonia: Pathophysiology (contd.) Only when the capacity of the alveolar macrophages to ingest or kill the microorganisms is exceeded does clinical pneumonia become manifest. The alveolar macrophages initiate the inflammatory response to bolster lower respiratory tract defenses. Mediators Responsible Effects IL-1 and TNF Fever IL – 8 , GCSF stimulates r elease & attraction of neutrophils to the lungs Causes peripheral leucocytosis, increased purulent secretions Inflammatory mediators (macrophages) & neutrophils Localised alveolar capillary leak Table 2: Mediators responsible in patho-physiology of Pneumonia

10. Pneumonia: Pathophysiology (contd.) Mechanism Clinical Features Leaky alveolar capillaries Hemoptysis Radiologic infiltrates Rales on auscultation Alveolar filling and action of bacterial pathogens Hypoxemia Decreased compliance of lungs Dyspnoea Reduction in lung volume and compliance Intra-pulmonary shunting of blood Death

11. Stages/Phases of Pneumonia Characteristic Features Oedematous Phase Alveoli filled with proteinaceous exudate and bacteria Rapidly followed by Red hepatization phase Stage of Red hepatization Presence of erythrocytes in the cellular intraalveolar exudate Neutrophil influx Bacteria can be seen in specimens Stage of Gray hepatization (successful containment of the infection & improvement in gas exchange) Erythrocytes extravasation ceases, extravasated ones get lysed and degraded Neutrophils predominant Abundant fibrin deposition Disappearance of bacteria Stage of Resolution Macrophages reappear Debris (PMN, Bacteria, fibrin) cleared Inflammatory response cleared Pneumonia: Pathology Table 3: Different Pathologic Phases of Pneumonia *Has been described best for lobar pneumococcal pneumonia.

12. CAP & HAP: A Comparison Community Acquired Hospital Acquired Definition It indicates pneumonia occuring in a person in a community (outside hospital) Refers to a new episode of pneumonia occurring at least 2 days after admission to hospital. Predisposing Factors Cigarette smoking Upper respiratory tract infections Alcohol Corticosteroid therapy Old age Recent influenza infection Indoor air pollution Reduced host defences against bacteria Aspiration of nasopharyngeal/gastric secretions Bacteria introduced into lower respiratory tract Bacteraemia Mode of Spread Droplet Infection Infecting Agent S. Pneumoniae, S. aureus, H. influenza Viruses (influenza, parainfluenza , measles, Herpes simplex, Varicella , CMV) Early-Onset: similar to CAP Late-Onset: Escherichia, Pseudomonas, Klebsiella , MRSA, anaerobes

13. CAP & HAP: Presentation(contd.) Community Acquired Hospital Acquired Can vary from indolent to fulminating presentation Pulmonary Symptoms : breathlessness, cough,-non-productive or productive ( mucoid , purulent , blood stained) haemoptysis, plueritic chest pain, may able to speak sentences/ short of breath Systemic Features : fever a/w chills n rigors, tachycardia, vomiting, decreased appetite, headache, fatigue, myalgias , arthralgia Elderly : New-onset/ progressive confusion Severely ill : septic shock or organ-failure Tachypnoea , use of accessory muscles, increased/decreased vocal fremitus, Percussion note: dull to flat Bronchial Breathing, Crackles Whispering pectoriloquy , pleural friction rub Universally agreed diagnostic criteria lacking Should be considered in any hospitalised / ventilated patient who develops: purulent sputum (or endotracheal secretions), new radiological infiltrates, an otherwise unexplained increase in oxygen requirement, a core temperature > 38.3°C, and leucocytosis or leucopenia .

14. CAP & HAP: Investigation Community Acquired Hospital Acquired Chest Radiology: to confirm the diagnosis and to exclude complications Pulse oximetry to monitor response to oxygen therapy, if SaO 2 < 93%, features of severe pneumonia, identify ventilatory failure or acidosis Cell count: neutrophil leucocytosis Microbiologic Studies: for severe CAP and for those that do not respond to initial therapy (Gram stain, sputum culture, blood culture, Polymerase Chain Reaction, Serology, Antigen Detection) Renal Function Tests: Urea & electrolytes Liver Function Tests Elevated C-Reactive Protein Circulating biomarkers may assist with the diagnosis but are currently non-specific. Appropriate investigations are similar to CAP, microbiological confirmation preferrable . In mechanically ventilated patients, bronchoscopy -directed protected brush specimens or bronchoalveolar lavage (BAL) may be performed. Endotracheal aspirates are easy to obtain but less reliable.

15. Chest Radiology In Pneumonia Left Lobar Pneumonia with pleural effusion Right Middle Lobar Pneumonia Right Upper Lobar Pneumonia Right Upper Lobe Pneumonia with air bronchograms

16. Hospital Care Associated Pneumonia HCAP represents a transition between classic CAP and typical HAP Refers to the development of pneumonia in a person who has spent at least 2 days in hospital within the last 90 days, attended a haemodialysis unit, received intravenous antibiotics, or been resident in a nursing home or other long-term care facility. (Davidson-21 st Ed.) MRSA in particular is more common in HCAP than in traditional HAP/VAP. Patients at greatest risk for HCAP are not well defined. Patients from nursing homes are not always at elevated risk for infection with MDR pathogens. Low risk of MDR infection if they have not recently received antibiotics and are independent in most activities of daily living. Patients receiving home infusion therapy or undergoing chronic dialysis are probably at particular risk for MRSA pneumonia In general, management of HCAP due to MDR pathogens is similar to that of MDR HAP/VAP.

17. Pneumonia: Severity Assessment There are currently two sets of criteria: Pneumonia Severity Index (PSI) , a prognostic model used to identify patients at low risk of dying; and CURB-65 criteria, a severity-of-illness score. Assessment for need for ICU care provided by severity criteria proposed by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) ≥ ≥ ≤ ≤ ≥

18. PSI Scoring System Pneumonia: Severity Assessment

19. CAP TREATMENT: GENERAL CONSIDERATION Adequate hydration, oxygen therapy for hypoxemia, and assisted ventilation Patients with severe CAP who remain hypotensive despite fluid resuscitation may have adrenal insufficiency and may respond to glucocorticoid treatment. Immunomodulatory therapy in the form of drotrecogin alfa (activated) should be considered for CAP patients with persistent septic shock and APACHE II scores of 25, particularly if the infection is caused by S . pneumoniae . Once the etiologic agent(s) and susceptibilities are known, therapy may be altered to target the specific pathogen(s). Switch to oral treatment is appropriate as long as the patient can ingest and absorb the drugs, is hemodynamically stable, and is showing clinical improvement. The duration of treatment for CAP has generated considerable interest

20. Acute Physiology and Chronic Health Evaluation II APACHE II APACHE II Score = A ( Sum of APS points) + B (Age points) + C (Chronic health points) CAP Treatment: General Consideration

21. CAP: Empirical Treatment for Out-Patients Modality Regimen Previously healthy and no antibiotics in past 3 months: A macrolide [ clarithromycin (500 mg PO bid) or azithromycin (500 mg PO once, then 250 mg qd )] or Doxycycline (100 mg PO bid) Comorbidities or antibiotics in past 3 months: select an alternative from a different class A respiratory fluoroquinolone [ moxifloxacin (400 mg PO qd ), gemifloxacin (320 mg PO qd ), levofloxacin (750 mg PO qd )] or   A β - lactam [preferred: high-dose amoxicillin (1 g tid ) or amoxicillin/ clavulanate (2 g bid); alternatives: ceftriaxone (1–2 g IV qd ), cefpodoxime (200 mg PO bid), cefuroxime (500 mg PO bid)] plus a macrolide In regions with a high rate of "high-level" pneumococcal macrolide resistance, consider alternatives listed above for patients with comorbidities .

22. CAP: Empirical Treatment for In-Patients Modality Regimen Non ICU Patients A respiratory fluoroquinolone [ moxifloxacin (400 mg PO or IV qd ), gemifloxacin (320 mg PO qd ), levofloxacin (750 mg PO or IV qd )] A β - lactam [ cefotaxime (1–2 g IV q8h), ceftriaxone (1–2 g IV qd ), ampicillin (1–2 g IV q4–6h), ertapenem (1 g IV qd in selected patients)] plus a macrolide [oral clarithromycin or azithromycin or IV azithromycin (1 g once, then 500 mg qd )] ICU Patients A β - lactam [ cefotaxime (1–2 g IV q8h), ceftriaxone (2 g IV qd ), ampicillin-sulbactam (2 g IV q8h)] plus   Azithromycin or a fluoroquinolone

23. CAP: Empirical Treatment Special Concerns Organism being considered Treatment Regimen Pseudomonas An antipneumococcal , antipseudomonal β - lactam [ piperacillin / tazobactam (4.5 g IV q6h), cefepime (1–2 g IV q12h), imipenem (500 mg IV q6h), meropenem (1 g IV q8h)] plus either ciprofloxacin (400 mg IV q12h) or levofloxacin (750 mg IV qd ) The above β - lactams plus an aminoglycoside [ amikacin (15 mg/kg qd ) or tobramycin (1.7 mg/kg qd ) and azithromycin ] The above β – lactams plus an aminoglycoside plus an antipneumococcal fluoroquinolone CA-MRSA Add linezolid (600 mg IV q12h) or vancomycin (1 g IV q12h).

24. CAP TREATMENT: FAILURE TO RESPOND Patients who are slow to respond to therapy should be reevaluated at about day 3 (sooner if their condition is worsening rather than simply not improving) Check the drug, dose of the correct drug Pathogen resistant to the drug selected, or a sequestered focus (e.g., a lung abscess or empyema ). Consider possibility of an unsuspected pathogen (e.g., CA-MRSA, M . tuberculosis , or a fungus). Re-consider your Diagnosis: tuberculosis, pulmonary edema, pulmonary embolism, lung carcinoma, radiation and hypersensitivity pneumonitis , and connective tissue disease involving the lungs. Nosocomial superinfections —both pulmonary and extrapulmonary

25. HAP: Emperical Treatment Categories Treatment Patients without Risk Factors for MDR Pathogens   Ceftriaxone (2 g IV q24h) or  Moxifloxacin (400 mg IV q24h), ciprofloxacin (400 mg IV q8h), or levofloxacin (750 mg IV q24h) or  Ampicillin/sulbactam (3 g IV q6h) or Ertapenem (1 g IV q24h) Patients with Risk Factors for MDR Pathogens     1. A β - lactam : Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–12h) or Piperacillin / tazobactam (4.5 g IV q6h), imipenem (500 mg IV q6h or 1 g IV q8h), or meropenem (1 g IV q8h) plus 2. A second agent active against gram-negative bacterial pathogens: Gentamicin or tobramycin (7 mg/kg IV q24h) or amikacin (20 mg/kg IV q24h) or Ciprofloxacin (400 mg IV q8h) or levofloxacin (750 mg IV q24h) plus 3. An agent active against gram-positive bacterial pathogens: Linezolid (600 mg IV q12h) or Vancomycin (15 mg/kg, up to 1 g IV, q12h)

26. PNEUMONIA: COMPLICATIONS Para-pneumonic effusion Empyema Retention of sputum causing lobar collapse Pulmonary embolism and DVT Pneumothorax ( S. aureus ) Suppurative pneumonia/ lung abscess ARDS, renal failure, multi-organ failure Ectopic abscess formation ( S. aureus ), Metastatic infection Pericarditis , hepatitits , myocarditis , meningoencephalitis Pyrexia due to drug hypersensitivity Exacerbation of comorbid illnesses. Complicated pleural effusion: diagnostic/therapeutic tapping required If the fluid has a pH of <7, a glucose level of <2.2 mmol /L, and a lactate dehydrogenase concentration of >1000 U/L or if bacteria are seen or cultured, then the fluid should be drained; a chest tube is usually required.

27. PNEUMONIA: FOLLOW UP Fever and leukocytosis usually resolve within 2–4 days in otherwise healthy patients with CAP, but physical findings may persist longer. Chest radiographic abnormalities are slowest to resolve and may require 4–12 weeks to clear Patients may be discharged from the hospital once their clinical conditions are stable, with no active medical problems requiring hospital care. For a patient whose condition is improving and who (if hospitalized) has been discharged, a follow-up radiograph can be done ~4–6 weeks later. If relapse or recurrence is documented, particularly in the same lung segment, the possibility of an underlying neoplasm must be considered.

28. PNEUMONIA: PROGNOSIS Depends on Patient's age, Comorbidities , and Site of treatment (inpatient or outpatient). Young patients without comorbidity do well and usually recover fully after ~2 weeks. Older patients and those with comorbid conditions can take several weeks longer to recover fully. Overall mortality rate for the outpatient group is <1%. Overall mortality rate for Inpatient group is estimated at 10%, with ~50% of deaths directly attributable to pneumonia.

29. PNEUMONIA: PREVENTION The main preventive measure is vaccination. In the event of an influenza outbreak, unprotected patients at risk from complications should be vaccinated immediately and given chemoprophylaxis with either oseltamivir or zanamivir for 2 weeks—i.e., until vaccine-induced antibody levels are sufficiently high. Because of an increased risk of pneumococcal infection, even among patients without obstructive lung disease, smokers should be strongly encouraged to stop smoking. 7-valent pneumococcal conjugate vaccine: produces T cell–dependent antigens that result in long-term immunologic memory.

30. From our Department…. Sama Prasad, 55 years Male, non smoker, non alcohol consumer, resident of Bara, working as labour in cement factory for 15 yrs, married, Hindu, came to ED 6 days back with: Cough-productive, scanty, yellowish for 3 days Fever- a/w chills & rigors, not documented for 2 days Loss of appetite for 2 days No significant past medical, surgical, personal, family history

31. From our Department…. General Examination: Ill looking, conscious, oriented to time, place & person No signs of pallor, icterus , cyanosis, clubbing, koilonychiya , lymphadenopathy , edema, dehydration Febrile (100 o F), tachypnoeic (30 breaths/min), pulse 100 b/ miin , BP 110/60 mm of Hg Chest Examination: Inspection- B/L symmetrical & elliptical, use of accessory muscle present Palpation- no mediastinal shift, increased vocal fremitus over right infra-mammary region, reduced chest expansion on right side Percussion- dull note over same area Auscultation- decreased air entry & coarse crepitations over same area, wheeze over right subscapular area as well Other Systems Examination: No Significant Findings

32. From our Department…. Provisional Diagnosis: Right Middle Zone Pneumonia Investigations requested : Hb % - 10.25% TLC – 24,700, neutrophilic predominance RBC & Platelet count – Within normal limit Chest X-ray , Postero -Anterior View CURB-65 Score: 2/5; Hospital Supervised Treatment (Short stay Inpatient )