Introduction

The word "pneumonia" takes its origin from the ancient Greek word "pneumon," which means "lung," so the word "pneumonia" becomes "lung disease." Medically it is an inflammation of one or both lungs' parenchyma that is more often, but not always, caused by infections. The many causes of pneumonia include bacteria, viruses, fungi, and parasites. This article will focus on bacterial pneumonia, as it is the major cause of morbidity and mortality. According to the new classification of pneumonia, there are four categories: community-acquired (CAP), hospital-acquired (HAP), healthcare-associated (HCAP) and ventilator-associated pneumonia (VAP). [1][2][3]

Types of Bacterial Pneumonia

• CAP: The acute infection of lung tissue in a patient who has acquired it from the community or within 48 hours of the hospital admission.
• HAP: The acute infection of lung tissue in a non-intubated patient that develops after 48 hours of hospitalization.
• VAP: A type of nosocomial infection of lung tissue that usually develops 48 hours or longer after intubation for mechanical ventilation.
• HCAP: The acute infection of lung tissue acquired from healthcare facilities such as nursing homes, dialysis centers, and outpatient clinics or from a patient with a history of hospitalization within the past three months.

Some articles include both HAP and VAP under the category of HCAP, so defining HCAP is problematic and controversial.

Etiology

Community-acquired pneumonia can be caused by an extensive list of agents that include bacteria, viruses, fungi, and parasites, but this article will focus on bacterial pneumonia and its causes. Bacteria have classically been categorized into two divisions on the basis of etiology, "typical" and "atypical" organisms. Typical organisms can be cultured on standard media or seen on Gram stain, but "atypical" organisms do not have such properties. [4]

• Typical pneumonia refers to pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria.
• Atypical pneumonia is mostly caused by Legionella, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Chlamydia psittaci.

The most common cause of community-acquired pneumonia (CAP) is S. pneumoniae, followed by Klebsiella pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa. The most common causes of HCAP and HAP are MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa, respectively. The causative agents of VAP include both multi-drug resistant (MDR) agents (e.g., S. pneumoniae, other Strep spp, H. influenzae and MSSA) and non-MDR (e.g., P. aeruginosa, methicillin-resistant Staphylococcus aureus, Acinetobacter spp. and antibiotic-resistant Enterobacteriaceae) bacterial pathogens.

Epidemiology

In the United States, lower respiratory tract infections account for more morbidity and mortality than any other infection. [5] The incidence of CAP in the United States is more than 5 million per year; 80% of these new cases are treated as outpatients with the mortality rate of less than 1%, and 20% are treated as inpatients with the mortality rate of 12% to 40%.

The incidence of CAP varies among different genders; for example, it is more common in males and African Americans than females and other Americans. However, the total number of deaths has been on the rise among females. [6] The incidence rates are higher at extremes of age; the adult rate is usually 5.15 to 7.06 cases per 1000 persons per year, but in the population of age less than 4 years and greater than 60 years, the rate is more than 12 cases per 1000 persons. In 2005, influenza and pneumonia combined was the eighth most common cause of death in the United States and the seventh most common cause of death in Canada. The mortality rate is variable among different regions, such as 7.3% for the United States and Canada, 9.1% for Europe, and 13.3% for Latin America.[7][8]

Pathophysiology

The lower respiratory tract is not sterile, and it always is exposed to environmental pathogens. Invasion and propagation of the above-mentioned bacteria into lung parenchyma at alveolar level causes bacterial pneumonia, and the body's inflammatory response against it causes the clinical syndrome of pneumonia.

To prevent this proliferation of microorganisms there are a number of host defenses working together in lungs such as mechanical (e.g., hair in nostrils and mucus on nasopharynx and oropharynx) and chemical (e.g., proteins produced by alveolar epithelial cells like surfactant protein A and D, which have the intrinsic property of opsonizing bacteria). Another component of the pulmonary defense system is made up of immune cells such as alveolar macrophages, which work to engulf and kill proliferating bacteria, but once bacteria overcome the capacity of host defenses, they start proliferating. In this setting, the alveolar macrophages kickoff the inflammatory response to strengthen the lower respiratory tract defenses. This inflammatory response is the main reason for the clinical manifestation of bacterial pneumonia. Cytokines are released in response to the inflammatory reaction and cause the constitutional symptoms, for example, IL-1 (interleukin-1) and TNF (tumor necrosis factor) cause fever. Chemokine-like IL-8 (interleukin-8) and colony-stimulating factors like G-CSF (granulocyte colony-stimulating factor) promote chemotaxis and neutrophils maturation respectively, resulting in leukocytosis on serological lab and purulent secretions. These cytokines are responsible for the leakage of the alveolar-capillary membrane at the site of inflammation, causing a decrease in compliance and shortness of breath. Sometimes even erythrocytes cross this barrier and result in hemoptysis.[9][10][11]

Histopathology

Pathologically, lobar pneumonia is the acute exudative inflammation of a lung lobe. It has the following four advanced stages if left untreated:

1. Congestion: In this stage, pulmonary parenchyma is not fully consolidated, and microscopically, the alveoli have serous exudates, pathogens, few neutrophils, and macrophages.
2. Red hepatization: In this stage, the lobe becomes consolidated, firm, and liver-like. Microscopically, there is an addition of fibrin along with serous exudate, pathogens, neutrophils, and macrophages. The capillaries are congested, and the alveolar walls are thickened.
3. Gray hepatization: The lobe is still liver-like in consistency but gray in color due to suppurative and exudate-filled alveoli.
4. Resolution: After a week, it starts resolving as lymphatic drainage or a productive cough clears the exudate.

History and Physical

While taking the history, it is crucial to explore the patient's potential exposures, risks of aspiration, host factors, and presenting symptoms.

Exposure: A detailed history of possible exposures should be sought as it can help in establishing the potential etiologies. The following are some associations of exposures and etiologies of bacterial pneumonia:

• Contaminated air-conditioning and water systems may cause legionella pneumonia
• Crowded places, such as jails, shelters, etc. expose a person to streptococcus pneumonia, mycobacteria, mycoplasma, and chlamydia
• Exposures to several animals, such as cats sheep, and cattle may lead to infection with Coxiella burnetii
• Some birds, such as chickens, turkeys, and ducks, can expose a person to Chlamydia psittaci.

Risks of Aspiration: Patients who have an increased risk of aspiration are more prone to develop pneumonia secondary to aspiration. Associated risks are:

• Altered mentation
• Drug abuse
• Dysphagia
• Gastroesophageal reflux disease (GERD)
• Alcoholism
• Seizure disorder

Host mechanisms: It is of utmost importance to explore a detailed history to find clues towards the etiology of pneumonia. For instance, a history of asthma, COPD, smoking, and immunocompromised status can be indicative of H influenzae infection. H influenza most commonly appears in the winter season. Similarly, social, sexual, medication and family history can all be useful in determining the cause of illness.

Features in the history of bacterial pneumonia may vary from indolent to fulminant. Clinical manifestation includes both constitutional findings and findings due to damage to the lung and related tissue. The following are significant history findings:

• Fever with tachycardia and/or chills and sweats.
• The cough may be either nonproductive or productive with mucoid, purulent or blood-tinged sputum.
• Pleuritic chest pain if the pleura is involved.
• Shortness of breath with normal daily routine work.
• Other symptoms include fatigue, headache, myalgia, and arthralgia.

For unbeknownst reasons, the presence of rigors is more often indicative of pneumococcal pneumonia than other bacterial pathogens. [12]

The presence of productive cough is the most common and significant presenting symptom. Some bacterial causes have particular manifestation, such as:

• S pneumoniae - Rust-colored sputum
• Pseudomonas, Hemophilus - Green sputum
• Klebsiella - Red currant-jelly sputum
• Anaerobes - foul-smelling and bad-tasting sputum

Atypical pneumonia presents with pulmonary and extra-pulmonary manifestations, such as Legionella pneumonia, often presents with altered mentation and gastrointestinal symptoms.

Physical findings also vary from patient to patient and mainly depend on the severity of lung consolidation, the type of organism, the extent of the infection, host factors, and existence or nonexistence of pleural effusion. The following are major clinical findings:

• Increased temperature (usually more than 38 C or 100.4 F)[13]
• Decreased temperature (less than 35 C or 95 F)
• Increased respiratory rate (more than 18 breaths/min)
• Increased heart rate (more than 100/min)
• Bradycardia (less than 60/min)
• Cyanosis
• Percussion sounds vary from flat to dull
• Tactile fremitus
• Crackles, rales, and bronchial breath sounds are heard on auscultation
• Tracheal deviation
• Lymphadenopathy
• Pleural rub
• Egophony

Confusion manifests earlier in older patients. A critically ill patient may present with sepsis or multi-organ failure.

Some examination findings are specific for certain etiologies, such as:

• Bradycardia - Legionella
• Dental illnesses - Anaerobes
• Impaired gag reflex - Aspiration pneumonia
• Cutaneous nodules - Nocardiosis
• Bullous myringitis - Mycoplasma.

Evaluation

The approach to evaluate and diagnose pneumonia depends on the clinical status, laboratory parameters, and radiological evaluation.[14]

• Clinical Evaluation: It includes taking a careful patient history and performing a thorough physical examination to judge the clinical signs and symptoms mentioned above.
• Laboratory Evaluation: This includes lab values such as complete blood count with differentials, inflammatory biomarkers like ESR and C-reactive protein, blood cultures, sputum analysis or Gram staining and/or urine antigen testing or polymerase chain reaction for nucleic acid detection of certain bacteria.
• An arterial blood gas may reveal hypoxia and respiratory acidosis.
• Pulse oximetry of less than 92% indicates severe hypoxia and elevated CRP predicts a serious infection.[15]
• Blood cultures should be obtained before administering antibiotics. Unfortunately, they are only positive in 40% of cases.
• Sputum evaluation if good quality may reveal more than 25 WBC per low-power field and less than 10 squamous epithelial cells.
• Some bacterial causes present with specific biochemical evidence, such as Legionella may present with hyponatremia and microhematuria.

• Radiological Evaluation: It includes a chest x-ray as an initial imaging test and the finding of pulmonary infiltrates on plain film is considered as a gold standard for diagnosis when the lab and clinical features are supportive.[16][2]
• The chest x-ray may reveal a consolidation or parapneumonic effusion.
• Chest CT is done for complex cases where the cause is not known.
• Bronchoalveolar lavage is done in patients who are intubated and can provide samples for culture.

Treatment / Management

In all patients with bacterial pneumonia, empirical therapy should be started as soon as possible. The first step in treatment is a risk assessment to know whether the patient should be treated in an outpatient or inpatient setting. Cardiopulmonary conditions, age, and severity of symptoms affect risk for bacterial pneumonia, especially CAP.[17][18][19]

An expanded CURB-65 or CURB-65 pneumonia severity score can be used for risk quantification. It includes C = Confusion, U = Uremia (BUN greater than 20 mg/dL), R = Respiratory rate (greater than 30 per min), B = B.P (BP less than 90/60 mmHg) and age greater than 65 years. One point is scored for each of these risk factors. For a score of 0-1, outpatient treatment is advised. If the total score is 2 or more, it indicates medical ward admission. If the total score is 3 or more, it indicates ICU admission. Recommended therapy for different settings are as follows:

• Outpatient Setting: For patients having comorbid conditions ( e.g., diabetes, malignancy, etc.), the regimen is fluoroquinolone or beta-lactams + macrolide. For patients with no comorbid conditions, macrolide or doxycycline can be used empirically. Testing is usually not performed as the empiric regimen is almost always successful.
• Inpatient Setting (non-ICU): Recommended therapy is fluoroquinolone or macrolide + beta-lactam.
• Inpatient Setting (ICU): Recommended therapy is beta-lactam + macrolide or beta-lactam + fluoroquinolone.
• MRSA: Vancomycin or linezolid can be added.

After getting a culture-positive lab result, therapy should be altered according to the culture-specific pathogen.

The patient also can benefit from smoking cessation, counseling, and vaccination for influenza and pneumococcus.

All patients treated at home should be scheduled for a follow-up visit within 2 days to assess any complication of pneumonia.

The role of corticosteroids remains controversial and may be used in patients who remain hypotensive with presumed adrenal insufficiency.

Other measures:

• Hydration
• Chest physical therapy
• Monitoring with pulse oximetry
• Upright positioning
• Respiratory therapy with bronchodilators
• Mechanical support if patients are in respiratory distress
• Nutrition
• Early mobilization

Differential Diagnosis

Distinguishing pneumonia from other pulmonary diseases can be a daunting task, particularly in patients with co-existing pulmonary pathology. The differential diagnoses are different for children and adults, as mentioned below:

Differential Diagnosis in Children

• Asthma or reactive airway disease
• Bronchiolitis
• Croup
• Respiratory distress syndrome
• Epiglottitis

Differential Diagnosis in Adults

• Acute and chronic bronchitis
• Aspiration of a foreign body
• Asthma
• Atelectasis
• Bronchiectasis
• Bronchiolitis
• Chronic obstructive pulmonary disease
• Fungal
• Lung abscess
• Pneumocystis jiroveci pneumonia
• Respiratory failure
• Viral infection

Prognosis

Prognosis of pneumonia depends on many factors including age, comorbidities, and hospital setting (inpatient or outpatient). Generally, the prognosis is promising in otherwise healthy patients. Patients older than 60 years or younger than 4 years of age have relatively poorer prognosis than young adults. If pneumonia is left untreated, the overall mortality may become 30%. Antibiotic resistance is very concerning due to the excessive and unjustified use of antibiotics. The Pneumonia Severity Index (PSI) may be utilized as a tool to establish a patient's risk of mortality.

A study conducted on etiologies of CAP, S pneumoniae was found to be the cause of mortality in most patients; however, Pseudomonas, Staphylococcus aureus, and mixed etiologies had the highest mortality rates in those affected. [20]

Complications

The most common complications of bacterial pneumonia are respiratory failure, sepsis, multiorgan failure, coagulopathy, and exacerbation of preexisting comorbidities. Other potential complications of bacterial pneumonia include:

• Lung fibrosis
• Destruction of lung parenchyma
• Necrotizing pneumonia
• Cavitation
• Empyema
• Pulmonary abscess
• Meningitis
• Death

Deterrence and Patient Education

Patients should be counseled to quit smoking, to abstain from alcohol intoxication, and to keep dental hygiene. Furthermore, to prevent bacterial pneumonia, recommendations include:

• Vaccination against pneumococcus
• The annual vaccine against H influenza

Elderly and immunocompromised patients should be instructed to seek medical assistance as soon as they develop symptoms such as dyspnea, rigors, or fever.

Pearls and Other Issues

1. Most patients respond with improvement within 48-72 hours.
2. The chest x-ray findings lag behind clinical features and may take 6-12 weeks to clear.
3. If patients fail to improve within 72 hours, another cause should be suspected, antibiotic resistance or development of complications like empyema.

Enhancing Healthcare Team Outcomes

The management of pneumonia requires an interprofessional team. The reason is that most patients are managed as outpatients, but if not properly treated, the morbidity and mortality are high.

Besides the administration of antibiotics, these patients often require chest physical therapy, a dietary consult, physical therapy to help regain muscle mass, and a dental consult. The key is to educate the patient on the discontinuation of smoking and abstaining from alcohol.

Patients need to be referred to a dietitian to ensure that they are eating healthy.

Further, the clinicians should encourage patients to get appropriate influenza and pneumococcal vaccines. The pharmacist should not only teach about antibiotic compliance but ensure that the patient is prescribed the right antibiotics aimed at the target organism. An infectious disease specialty-trained pharmacist is particularly helpful in assisting the team with difficult antibiotic treatment choices. Nursing can counsel on the appropriate dosing and administration of medications and answer patient questions, as well as charting treatment progress, and reporting any issues to the clinician managing the case.

Finally, it is important to educate the patient to follow up with clinicians if they want a complete resolution of the infectious process.[19][21] (Level V) Only with open communication between the interprofessional team can the morbidity of pneumonia be lowered.

Outcomes

In healthy people, the outcome after bacterial pneumonia is excellent. However, in people with advanced age, lung disease, immunosuppression, infection with aggressive gram-negative organisms (Klebsiella), and other comorbidities, the outcomes are usually poor. When pneumonia is left untreated, it carries mortality in excess of 25%. Pneumonia can also lead to extensive lung damage and lead to residual impairment in lung function. Other reported complications of pneumonia that occur in 1-5% of patients include lung abscess, empyema, and bronchiectasis.[22][23] (Level V)

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