Pneumonia - Community-Acquired Disease Background

Introduction 

Pneumonia is an acute infection of the pulmonary parenchyma accompanied by symptoms of acute illness and abnormal chest findings. It commonly presents with at least one abnormal chest finding of diminished breath sounds, rhonchi, crackles, or wheezing, and X-ray may show lobar consolidation, bilateral infiltrates, or cavitation. It occurs in the very young and the very old. It is a potentially life-threatening disease, especially in older adults and those with comorbid illnesses.

Epidemiology 

Pneumonia is still the leading cause of death from an infectious disease in both adults and children <5 years old. The rate is higher among the very young (children <5 years old) and the very old (adults >60 years of age). It is more common in men than in women.  

India comprises 23% of the pneumonia burden worldwide and has a case fatality rate of 14-30. In China, the two-week prevalence was 0.9% in 2003 and 1.1% in 2008.  

A study in South Korea reported that the hospitalization rate was 520 per 100,000 population in 2002-2005, the highest among those ≥75 years old. In rural Thailand, the estimated hospitalization rate ranged from 177-580 per 100,000 population in 2002-2003 and 199-256 per 100,000 population in 2006 based on epidemiological studies. In the Philippines, pneumonia is one of the top medical claims reimbursed through its largest insurance provider making it a significant public health concern in the country.  

It is the sixth major cause of morbidity and mortality. In the Asia-Pacific region, mortality is estimated at 1.1-30%, with Japan, India, Philippines, Pakistan, Malaysia, and Cambodia having the highest mortality rates. Mortality is higher in patients who are hospitalized, with comorbidities, those belonging to low-income countries, in nursing homes, or with advanced age.

Etiology 

In most patients with community-acquired pneumonia (CAP), the causative organism is unknown and the success rate in determining the etiologic agent is usually about 50%.  

Streptococcus pneumoniae is the most frequently isolated organism. Other commonly identified pathogens include Haemophilus influenzae, atypical pathogens (eg Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Chlamydophila psittaci) and viruses, which may account for 10-20% of cases.  

Drug-resistant Streptococcus pneumoniae (DRSP) may be found in patients with antibiotic use within the past 3 months, alcoholism, >65 years old, immunosuppression, or resident of nursing homes. Gram-negative bacilli (Enterobacteriaceae and Pseudomonas aeruginosa) are frequent causative agents in patients who have had previous antimicrobial treatment or who have pulmonary comorbidities (eg bronchiectasis or chronic obstructive pulmonary disease [COPD]). Anaerobes are usually associated with aspiration pneumonia.

Pathophysiology 

The development of community-acquired pneumonia may be due to microaspiration, presence of a defect in the host defenses, possible exposure to a virulent microorganism, or due to presence of an overwhelming inoculum. Microaspiration is a mechanism by which the constituents of both the microbiota and pathogens reach the lungs. Other mechanisms by which a pathogen gains access to the lungs are via hematogenous spread, contiguous spread, and macroaspiration.  

The following are the virulence factors of some causative agents of community-acquired pneumonia: 

• Chlamydia pneumoniae possesses ciliostatic factor
• Mycoplasma pneumoniae shears off the cilia
• Influenza virus causes a marked reduction in the tracheal mucus velocity for up to 12 weeks post-infection
• Streptococcus pneumoniae and Neisseria meningitides produce proteases and split secretory IgA; other virulence factors include inhibition of phagocytosis, pneumolysin, and thiol-activated cytolysin
• Mycobacterium sp, Nocardia sp, and Legionella sp are all resistant to microbicidal activity (phagocytes)

Risk Factors 

• Administration of immunosuppressive agents (eg recipients of solid organ or stem cell transplants or those receiving chemotherapy, and long-term steroids)
• Comorbid conditions:
  • Chronic respiratory disease (eg bronchial asthma, chronic bronchitis, cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, pulmonary edema)
  • Genetic disorder (eg Kartagener's syndrome)
  • Influenza
  • Chronic renal disorders
  • Hepatic conditions
  • Diabetes mellitus
  • Malignancy (eg myeloma, lung cancer)
  • Immunocompromised states such as human immunodeficiency virus (HIV) infection, hypogammaglobulinemia (IgG2 immunodeficiency), hyperimmunoglobulin E (Job) syndrome, surgical asplenia, or sickle cell disease 
• Continual contact with children (eg young children attending childcare, preschool teachers)
• Cigarette smoking and alcoholism
• Elderly (>65 years old)
• Immunosuppression and malnutrition
• Medications (eg inhaled corticosteroids, proton pump inhibitors and H₂ blockers, antipsychotic drugs, and sedatives) 
• Oxygen and inhalation therapy particularly containing steroids or using plastic spacers
• Other risk factors for young adults include training in the military and presence of low cholesterol or albumin levels
• People who are homeless and overcrowding inside jails and human shelters 

Classification 

Community-acquired pneumonia may be classified as low-, moderate-, or high-risk depending on the patient’s overall clinical status, vital signs, presence of co-morbidities, and chest X-ray findings.

Low-risk Community-acquired Pneumonia (CAP)  

Low-risk community-acquired pneumonia is associated with low morbidity and mortality rate of <5% and is therefore suitable for outpatient care. Patients considered at low-risk community-acquired pneumonia are those with stable vital signs and stable comorbid conditions (eg controlled diabetes mellitus [DM], coronary artery disease [CAD], renal insufficiency, COPD, chronic liver disease, chronic alcohol abuse, and asplenia).  

They may be treated as outpatients with a reasonable assurance of follow-up and sufficient social support. Hospitalization of patients with low-risk community-acquired pneumonia may be required if there are complications of pneumonia itself, exacerbation of underlying diseases, advanced age (≥65 years of age), inability to reliably take oral medications or receive outpatient care, inability to maintain oral intake, uncontrollable vomiting, cognitive dysfunction, and social problems (eg unavailability of a caregiver, homelessness).  

The possible pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis, and enteric Gram-negative bacilli (among those with comorbid illnesses).

Moderate-risk Community-acquired Pneumonia (CAP)  

Moderate-risk community-acquired pneumonia is associated with a complicated outcome and higher mortality rate, thus in-hospital parenteral therapy is recommended. In patients with prior respiratory tract colonization, culture, swab, or polymerase chain reaction (PCR) tests must be taken prior to starting empiric therapy.  

The possible pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis, enteric Gram-negative bacilli, Legionella pneumophila, and anaerobes (in patients with risk of aspiration).

High-risk Community-acquired Pneumonia (CAP)  

High-risk community-acquired pneumonia is associated with a mortality rate of 36%, thus it is managed in a hospital setting and those with hemodynamic instability or respiratory failure should be admitted to the intensive care unit (ICU).  

The possible pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis, enteric Gram-negative bacilli, Legionella pneumophila, Staphylococcus aureus, Pseudomonas aeruginosa, Pneumocystis jirovecii, Klebsiella pneumoniae, Acinetobacter sp, and anaerobes (in patients with risk of aspiration).  

Patients who have a history of chronic (>7 days within the past month) use of broad-spectrum antibiotic therapy, bronchiectasis, malnutrition, and on steroid therapy are at risk of developing Pseudomonas aeruginosa infection.