Author:Dr. Ratan Vaish

Pneumonia is an infection of the pulmonary parenchyma. Despite being the cause of significant morbidity and mortality, pneumonia is often misdiagnosed, mistreated, and underestimated. Pneumonia was typically classified as community-acquired (CAP), hospital-acquired (HAP), or ventilator-associated (VAP).

ETIOLOGY
Various causes of CAP includes bacteria, fungi, viruses, and protozoa. Newly identified pathogens include metapneumo viruses, the corona viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, and community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA). Most cases of CAP, however, are caused by relatively few pathogens. Although Streptococcus pneumoniae is most common, other organisms also must be considered in light of the patient’s risk factors and severity of illness. Typical” bacterial pathogens includes S. pneumoniae, Haemophilus influenzae, and (in selected patients) S. aureus and gram-negative bacilli such as Klebsiella pneumoniae and Pseudomonas aeruginosa. The “atypical” organisms include Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species (in inpatients) as well as respiratory viruses such as influenza viruses, adenoviruses, human metapneumo virus, and respiratory syncytial viruses. Viruses may be responsible for a large proportion of CAP cases that require hospital admission, even in adults.

EPIDEMIOLOGY
More than 5 million CAP cases occur annually in the United States; usually, 80% of the affected patients are treated as outpatients and 20% as inpatients. The mortality rate among outpatients is usually ≤1%, whereas among hospitalized patients the rate can range from ∼12% to 40%, depending on whether treatment is provided in or outside of the intensive care unit (ICU). CAP results in more than 1.2 million hospitalizations and more than 55,000 deaths annually. The overall yearly cost associated with CAP is estimated at $12 billion. The incidence rates are highest at the extremes of age. The overall annual rate in the United States is 12 cases/1000 persons, but the figure increases to 12–18/1000 among children 60 years of age. In United Kingdom an estimated 5-11/ 1000 adults suffer from CAP each year.

Factor Possible Pathogen(s)
Alcoholism treptococcus pneumoniae, oral anaerobes, Klebsiella pneumoniae, Acinetobacter spp., Mycobacterium tuberculosis
COPD and/or smoking Haemophilus influenzae, Pseudomonas aeruginosa, Legionella spp., S. pneumoniae, Moraxella catarrhalis, Chlamydia pneumonia
Structural lung disease (e.g., bronchiectasis) P. aeruginosa, Burkholderia cepacia, Staphylococcus aureus
Dementia, stroke, decreased level of consciousness Oral anaerobes, gram-negative enteric bacteria
Lung abscess CA-MRSA, oral anaerobes, endemic fungi, M. tuberculosis, atypical mycobacteria
Travel to Ohio or St. Lawrence river valleys Histoplasma capsulatum
Travel to southwestern United States Hantavirus, Coccidioides spp.
Travel to Southeast Asia Burkholderia pseudomallei, avian influenza virus
Stay in hotel or on cruise ship in previous 2 weeks Legionella spp.
Local influenza activity Influenza virus, S. pneumoniae, S. aureus
Exposure to bats or birds H. capsulatum
Exposure to birds Chlamydia psittaci
Exposure to rabbits Francisella tularensis
Exposure to sheep, goats, parturient cats Coxiella burnetii
Abbreviations: CA-MRSA, community-acquired methicillin-resistant Staphylococcus aureus; COPD, chronic obstructive pulmonary disease.


CLINICAL MANIFESTATIONS
CAP can vary from indolent to fulminant in presentation and from mild to fatal in severity. Manifestations of progression and severity include both constitutional findings and those limited to the lung and associated structures. In light of the pathobiology of the disease, many of the findings are to be expected. The patient is frequently febrile with tachycardia or may have a history of chills and/or sweats. Cough may be either nonproductive or productive of mucoid, purulent, or blood-tinged sputum. Gross hemoptysis is suggestive of CA-MRSA pneumonia. Depending on severity, the patient may be able to speak in full sentences or may be very short of breath. If the pleura is involved, the patient may experience pleuritic chest pain. Up to 20% of patients may have gastrointestinal symptoms such as nausea, vomiting, and/or diarrhea. Other symptoms may include fatigue, headache, myalgias, and arthralgias. Findings on physical examination vary with the degree of pulmonary consolidation and the presence or absence of a significant pleural effusion. An increased respiratory rate and use of accessory muscles of respiration are common. Palpation may reveal increased or decreased tactile fremitus, and the percussion note can vary from dull to flat, reflecting underlying consolidated lung and pleural fluid, respectively. Crackles, bronchial breath sounds, and possibly a pleural friction rub may be heard on auscultation. The clinical presentation may not be so obvious in the elderly, who may initially display new-onset or worsening confusion and few other manifestations. Severely ill patients may have septic shock and evidence of organ failure.

  • Differential diagnosis
  • Acute bronchitis
  • Acute exacerbations of
  • Chronic bronchitis
  • Heart failure
  • Pulmonary embolism
  • Hypersensitivity pneumonitis
  • Radiation pneumonitis



Investigations
CBC, RBS, Blood Urea, S. Creatinine, Urine examination, ECG, ECHO etc.

Chest radiography Chest radiography is often necessary to differentiate CAP from other conditions. Radiographic findings may include risk factors for increased severity (e.g., cavitation or multilobar involvement). Occasionally, radiographic results suggest an etiologic diagnosis. For example, pneumatoceles suggest infection with S. aureus, and an upper-lobe cavitating lesion suggests tuberculosis. CT may be of value in a patient with suspected postobstructive pneumonia caused by a tumor or foreign body or suspected cavitary disease.

Gram’s Stain and Culture of Sputum
Gram’s staining may identify certain pathogens (e.g., S. pneumoniae, S. aureus, and gram-negative bacteria) by their characteristic appearance.

Blood Cultures Urinary Antigen Tests
urinary antigen tests can detect pneumococcal and Legionella antigen in urine. Both tests can detect antigen even after the initiation of appropriate antibiotic therapy.

Polymerase Chain Reaction
Polymerase chain reaction (PCR) tests, which amplify a microorganism’s DNA or RNA, can detect the nucleic acid of Legionella species, M. pneumoniae, C. pneumoniae, and mycobacteria. In patients with pneumococcal pneumonia, an increased bacterial load in whole blood documented by PCR is associated with an increased risk of septic shock, the need for mechanical ventilation, and death.

Serology Biomarkers
The two currently in use are C-reactive protein (CRP) and procalcitonin (PCT).

Treatment
Certain patients clearly can be managed at home, and others clearly require treatment in the hospital, but the choice is sometimes difficult. Tools that objectively assess the risk of adverse outcomes, including severe illness and death, can minimize unnecessary hospital admissions. There are currently two sets of criteria: the Pneumonia Severity Index (PSI), a prognostic model used to identify patients at low risk of dying; and the CURB-65 criteria, a severity-of-illness score. To determine the PSI, points are given for 20 variables, including age, coexisting illness, and abnormal physical and laboratory findings. On the basis of the resulting score, patients are assigned to one of five classes with the following mortality rates: class 1, 0.1%; class 2, 0.6%; class 3, 2.8%; class 4, 8.2%; and class 5, 29.2%. Determination of the PSI is often impractical in a busy emergency department setting because of the number of variables that must be assessed. However, clinical trials demonstrate that routine use of the PSI results in lower admission rates for class 1 and class 2 patients. Patients in class 3 could ideally be admitted to an observation unit until a further decision can be made. The CURB-65 criteria include five variables: confusion (C); urea >7 mmol/L (U); respiratory rate ≥30/min (R); blood pressure, systolic ≤90 mmHg or diastolic ≤60 mmHg (B); and age ≥65 years. Patients with a score of 0, among whom the 30-day mortality rate is 1.5%, can be treated outside the hospital. With a score of 2, the 30-day mortality rate is 9.2%, and patients should be admitted to the hospital.

Risk Factors for Early Deterioration in CAP
Multilobar infiltrates, severe hypoxemia (arterial saturation <90%), severe acidosis (pH <7.30), mental confusion, severe tachypnea (>30 breaths/min), hypoalbuminemia, neutropenia, thrombocytopenia,hyponatremia and hypoglycemia etc. Among patients with scores of ≥3, mortality rates are 22% overall; these patients may require ICU admission.

Antibiotic Resistance
Antimicrobial resistance is a significant problem that threatens to diminish our therapeutic armamentarium. Misuse of antibiotics results in increased antibiotic selection pressure that can affect resistance locally or even globally by clonal dissemination.

Gram-Negative Bacilli
Fluoroquinolone resistance among isolates of Escherichia coli from the community appears to be increasing. Enterobacter species are typically resistant to cephalosporins; the drugs of choice for use against these bacteria are usually fluoroquinolones or carbapenems

Initial antibiotic management
initial therapy is usually empirical, designed to cover the most likely pathogens. In all cases, antibiotic treatment should be initiated as expeditiously as possible. Antibiotic Treatment of Community-Acquired Pneumonia

Outpatients
1. 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)
2. 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 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 macrolides
3. In regions with a high rate of “high-level” pneumococcal macrolide resistance, b consider alternatives listed above for patients with comorbidities.

Inpatients, Non-ICU
•A respiratory fluoroquinolone (e.g., moxifloxacin [400 mg PO or IV qd] or levofloxacin [750 mg PO or IV qd])
•A β-lactamc (e.g., ceftriaxone [1–2 g IV qd], ampicillin [1–2 g IV q4–6h], cefotaxime [1–2 g IV q8h], ertapenem [1 g IV qd]) plus a macrolides (e.g., oral clarithromycin or azithromycin [as listed above] or IV azithromycin [1 g once, then 500 mg qd])

Inpatients, ICU
•A β-lactame (e.g., ceftriaxone [2 g IV qd], ampicillin-sulbactam [2 g IV q8h], or cefotaxime [1–2 g IV q8h]) plus either azithromycin or a fluoroquinolone (as listed above for inpatients, non-ICU)

Special Concerns
If Pseudomonas is a consideration:
•An antipseudomonal β-lactam (e.g., 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]) plus azithromycin
•The above β-lactamsf plus an aminoglycoside plus an antipneumococcal fluoroquinolone


If CA-MRSA is a consideration:
• Add linezolid (600 mg IV q12h) or vancomycin (15 mg/kg q12h initially, with adjusted doses) A- Doxycycline (100 mg PO bid) is an alternative to the macrolide. B- MICs of >16 μg/mL in 25% of isolates. C- A respiratory fluoroquinolone should be used for penicillin-allergic patients. D -Doxycycline (100 mg IV q12h) is an alternative to the macrolide. E- For penicillin-allergic patients, use a respiratory fluoroquinolone and aztreonam (2 g IV q8h). F-For penicillin-allergic patients, substitute aztreonam.

Abbreviations: ICU, intensive care unit. A longer course may be required for patients with bacteremia, metastatic infection, or infection with a virulent pathogen such as P. aeruginosa or CA-MRSA.

GENERAL CONSIDERATIONS
In addition to appropriate antimicrobial therapy, Adequate hydration, oxygen therapy for hypoxemia, and assisted ventilation when necessary are critical to successful treatment. Patients with severe CAP who remain hypotensive despite fluid resuscitation may have adrenal insufficiency and may respond to glucocorticoid treatment.

Failure to Improve
Patients slow to respond to therapy should be reevaluated at about day 3 (sooner if their condition is worsening rather than simply not improving), and several possible scenarios should be considered. In all cases of delayed response or deteriorating condition, the patient must be carefully reassessed and appropriate studies initiated, possibly including such diverse procedures as CT or bronchoscopy.

Complications
respiratory failure, shock and multiorgan failure, coagulopathy, and exacerbation of comorbid illnesses. Three particularly noteworthy conditions are metastatic infection, lung abscess, and complicated pleural effusion. Metastatic infection (e.g., brain abscess or endocarditis) is very unusual and will require a high degree of suspicion and a detailed workup for proper treatment. Lung abscess may occur in association with aspiration or with infection caused by a single CAP pathogen, such as CA-MRSA, P. aeruginosa, or (rarely) S. pneumoniae. Aspiration pneumonia is typically a polymicrobial infection involving both aerobes and anaerobes. A significant pleural effusion should be tapped for both diagnostic and therapeutic purposes. 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 it should be completely drained; a chest tube is often required and video-assisted thoracoscopy may be needed for late treatment or difficult cases.

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 (4–12 weeks), with the speed of clearance depending on the patient’s age and underlying lung disease. Patients may be discharged from the hospital once their clinical conditions, including comorbidities, are stable. The site of residence after discharge (nursing home, home with family, home alone) is an important discharge timing consideration, particularly for elderly patients. For a hospitalized patient, a follow-up radiograph ∼4–6 weeks later is recommended. If relapse or recurrence is documented, particularly in the same lung segment, the possibility of an underlying neoplasm must be considered.

PROGNOSIS
The prognosis of CAP depends on the 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. The overall mortality rate for the outpatient group is <1%. For patients requiring hospitalization, the overall mortality rate is estimated at 10%, with ~50% of deaths directly attributable to pneumonia.

Prevention
Stop smoking, vaccinations (A pneumococcal polysaccharide vaccine (PPV23) , a protein conjugate pneumococcal vaccine (PCV13)), and Influenza vaccine. 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.

Refferences :

  1. British Thoracic Society Guidelines
  2. Andrew R et al. ( Cochrane Review ) Cochrane Library, issue 4, 2003. Oxford: update software
  3. Harrison`s principles of Internal Medicine, 19th Edition
  4. Davidson`s Principles & Practice of Medicine, 21st Edition