Pathogenesis, Clinical features, Diagnosis, and Management of Community Acquired Pneumonia

 INTRODUCTION:

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. The clinical presentation of CAP varies, ranging from mild pneumonia characterized by fever and productive cough to severe pneumonia characterized by respiratory distress and sepsis. Because of the wide spectrum of associated clinical features, CAP is a part of the differential diagnosis of nearly all respiratory illnesses.

DEFINITIONS:

Community-acquired pneumonia (CAP) refers to an acute infection of the pulmonary parenchyma acquired outside of the hospital.

●Nosocomial pneumonia refers to an acute infection of the pulmonary parenchyma acquired in hospital settings and encompasses both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).

•HAP refers to pneumonia acquired ≥48 hours after hospital admission.

•VAP refers to pneumonia acquired ≥48 hours after endotracheal intubation.

Risk factors:

Older age – The risk of CAP rises with age. The annual incidence of hospitalization for CAP among adults ≥65 years old is approximately 2000 per 100,000 in the United States. This figure is approximately three times higher than the general population and indicates that 2 percent of the older adult population will be hospitalized for CAP annually .

Chronic comorbidities – The comorbidity that places patients at highest risk for CAP hospitalization is chronic obstructive pulmonary disease (COPD), with an annual incidence of 5832 per 100,000 in the United States [7]. Other comorbidities associated with an increased incidence of CAP include other forms of chronic lung disease (eg, bronchiectasis, asthma), chronic heart disease (particularly congestive heart failure), stroke, diabetes mellitus, malnutrition, and immunocompromising conditions.

Viral respiratory tract infection – Viral respiratory tract infections can lead to primary viral pneumonias and also predispose to secondary bacterial pneumonia. This is most pronounced for influenza virus infection.

Impaired airway protection – Conditions that increase risk of macroaspiration of stomach contents and/or microaspiration of upper airway secretions predispose to CAP, such as alteration in consciousness (eg, due to stroke, seizure, anesthesia, drug or alcohol use) or dysphagia due to esophageal lesions or dysmotility.

Smoking and alcohol overuse – Smoking, alcohol overuse (eg, >80 g/day), and opioid use are key modifiable behavioral risk factors for CAP.

Other lifestyle factors – Other factors that have been associated with an increased risk of CAP include crowded living conditions (eg, prisons, homeless shelters), residence in low-income settings, and exposure to environmental toxins (eg, solvents, paints, or gasoline).

MICROBIOLOGY:

Common causes — Streptococcus pneumoniae (pneumococcus) and respiratory viruses are the most frequently detected pathogens in patients with CAP.

The most commonly identified causes of CAP can be grouped into three categories:

●Typical bacteria

•S. pneumoniae (most common bacterial cause)

•Haemophilus influenzae

•Moraxella catarrhalis

•Staphylococcus aureus

•Group A streptococci

•Aerobic gram-negative bacteria (eg, Enterobacteriaceae such as Klebsiella spp or Escherichia coli)

•Microaerophilic bacteria and anaerobes (associated with aspiration)

●Atypical bacteria ("atypical" refers to the intrinsic resistance of these organisms to beta-lactams and their inability to be visualized on Gram stain or cultured using traditional techniques)

•Legionella spp

•Mycoplasma pneumoniae

•Chlamydia pneumoniae

•Chlamydia psittaci

•Coxiella burnetii

●Respiratory viruses

•Influenza A and B viruses

•Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

•Other coronaviruses (eg, CoV-229E, CoV-NL63, CoV-OC43, CoV-HKU1)

•Rhinoviruses

•Parainfluenza viruses

•Adenoviruses

•Respiratory syncytial virus

•Human metapneumovirus

•Human bocaviruses

PATHOGENESIS:

CAP has been viewed as an infection of the lung parenchyma, primarily caused by bacterial or viral respiratory pathogens. In this model, respiratory pathogens are transmitted from person to person via droplets or, less commonly, via aerosol inhalation (eg, as with Legionella or Coxiella species). Following inhalation, the pathogen colonizes the nasopharynx and then reaches the lung alveoli via microaspiration. When the inoculum size is sufficient and/or host immune defenses are impaired, infection results. Replication of the pathogen, the production of virulence factors, and the host immune response lead to inflammation and damage of the lung parenchyma, resulting in pneumonia (figure 3).

With the identification of the lung microbiome, that model has changed [19-21]. While the pathogenesis of pneumonia may still involve the introduction of respiratory pathogens into the alveoli, the infecting pathogen likely has to compete with resident microbes to replicate. In addition, resident microbes may also influence or modulate the host immune response to the infecting pathogen. If this is correct, an altered alveolar microbiome (alveolar dysbiosis) may be a predisposing factor for the development of pneumonia.

In some cases, CAP might also arise from uncontrolled replication of microbes that normally reside in the alveoli. The alveolar microbiome is similar to oral flora and is primarily comprised of anaerobic bacteria (eg, Prevotella and Veillonella) and microaerophilic streptococci. Hypothetically, exogenous insults such as a viral infection or smoke exposure might alter the composition of the alveolar microbiome and trigger overgrowth of certain microbes. Because organisms that compose the alveolar microbiome typically cannot be cultivated using standard cultures, this hypothesis might explain the low rate of pathogen detection among patients with CAP.

In any scenario, the host immune response to microbial replication within the alveoli plays an important role in determining disease severity. For some patients, a local inflammatory response within the lung predominates and may be sufficient for controlling infection. In others, a systemic response is necessary to control infection and to prevent spread or complications, such as bacteremia. In a minority, the systemic response can become dysregulated, leading to tissue injury, sepsis, acute respiratory distress syndrome, and/or multiorgan dysfunction.

CLINICAL PRESENTATION:

The clinical presentation of CAP varies widely, ranging from mild pneumonia characterized by fever, cough, and shortness of breath to severe pneumonia characterized by sepsis and respiratory distress. Symptom severity is directly related to the intensity of the local and systemic immune response in each patient.

●Pulmonary signs and symptoms – Cough (with or without sputum production), dyspnea, and pleuritic chest pain are among the most common symptoms associated with CAP. Signs of pneumonia on physical examination include tachypnea, increased work of breathing, and adventitious breath sounds, including rales/crackles and rhonchi. Tactile fremitus, egophony, and dullness to percussion also suggest pneumonia. These signs and symptoms result from the accumulation of white blood cells (WBCs), fluid, and proteins in the alveolar space. Hypoxemia can result from the subsequent impairment of alveolar gas exchange. On chest radiograph, accumulation of WBCs and fluid within the alveoli appears as pulmonary opacities.

●Systemic signs and symptoms – The great majority of patients with CAP present with fever. Other systemic symptoms such as chills, fatigue, malaise, chest pain (which may be pleuritic), and anorexia are also common. Tachycardia, leukocytosis with a leftward shift, or leukopenia are also findings that are mediated by the systemic inflammatory response. Inflammatory markers, such as the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin may rise, though the latter is largely specific to bacterial infections. CAP is also the leading cause of sepsis; thus, the initial presentation may be characterized by hypotension, altered mental status, and other signs of organ dysfunction such as renal dysfunction, liver dysfunction, and/or thrombocytopenia.

Diagnosis:

A chest X-ray looks for inflammation in your lungs. A chest X-ray is often used to diagnose pneumonia.

Blood tests, such as a complete blood count (CBC) see whether your immune system is fighting an infection.

Pulse oximetry measures how much oxygen is in your blood. Pneumonia can keep your lungs from getting enough oxygen into your blood. To measure the levels, a small sensor called a pulse oximeter is attached to your finger or ear.

A blood gas test may be done if you are very sick. For this test, your provider measures your blood oxygen levels using a blood sample from an artery, usually in your wrist. This is called an arterial blood gas test.

A sputum test, using a sample of sputum (spit) or mucus from your cough, may be used to find out what germ is causing your pneumonia.

A blood culture test can identify the germ causing your pneumonia and also show whether a bacterial infection has spread to your blood.

A polymerase chain reaction (PCR) test quickly checks your blood or sputum sample to find the DNA of germs that cause pneumonia.

A bronchoscopy looks inside your airways. If your treatment is not working well, this procedure may be needed. At the same time, your doctor may also collect samples of your lung tissue and fluid from your lungs to help find the cause of your pneumonia.

A chest computed tomography (CT) scan can show how much of your lungs are affected by pneumonia. It can also show whether you have complications such as lung abscesses or pleural disorders. A CT scan shows more detail than a chest X-ray.

A pleural fluid culture can be taken using a procedure called thoracentesis, which is when a doctor uses a needle to take a sample of fluid from the pleural space between your lungs and chest wall. The fluid is then tested for bacteria.

DIFFERENTIAL DIAGNOSIS:

Congestive heart failure with pulmonary edema

•Pulmonary embolism

•Pulmonary hemorrhage

•Atelectasis

•Aspiration or chemical pneumonitis

•Drug reactions

•Lung cancer

•Collagen vascular diseases

•Vasculitis

•Acute exacerbation of bronchiectasis

•Interstitial lung diseases (eg, sarcoidosis, asbestosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia)

TREATMENT:

Outpatient antibiotic therapy:

For most patients aged <65 years who are otherwise healthy and have not recently used antibiotics, we typically use oral amoxicillin (1 g three times daily) plus a macrolide (eg, azithromycin or clarithromycin) or doxycycline. Generally, we prefer to use a macrolide over doxycycline.

This approach differs from the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA), which recommend monotherapy with amoxicillin as first line and monotherapy with either doxycycline or a macrolide (if local resistance rates are <25 percent [eg, not in the United States]) as alternatives for this population [26]. The rationale for each approach is discussed separately. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Empiric antibiotic treatment'.)

●For patients who have major comorbidities (eg, chronic heart, lung, kidney, or liver disease, diabetes mellitus, alcohol dependence, or immunosuppression), who are smokers, and/or who have used antibiotics within the past three months, we suggest oral amoxicillin-clavulanate (875 mg twice daily or extended release 2 g twice daily) plus either a macrolide (preferred) or doxycycline.

Inpatient antibiotic therapy:

For patients without suspicion for MRSA or Pseudomonas, we generally use one of two regimens: combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone. Because these two regimens have similar clinical efficacy, we select among them based on other factors (eg, antibiotic allergy, drug interactions). For patients who are unable to use either a macrolide or a fluoroquinolone, we use a beta-lactam plus doxycycline.

●For patients with known colonization or prior infection with Pseudomonas, recent hospitalization with IV antibiotic use, or other strong suspicion for pseudomonal infection, we typically use combination therapy with both an antipseudomonal beta-lactam (eg, piperacillin-tazobactam, cefepime, ceftazidime, meropenem, or imipenem) plus an antipseudomonal fluoroquinolone (eg, ciprofloxacin or levofloxacin). The selection of empiric regimens should also be informed by the susceptibility pattern for prior isolates.

●For patients with known colonization or prior infection with MRSA or other strong suspicion for MRSA infection, we add an agent with anti-MRSA activity, such as vancomycin or linezolid, to either of the above regimens. We generally prefer linezolid over vancomycin when community-acquired MRSA is suspected (eg, a young, otherwise healthy patient who plays contact sports presenting with necrotizing pneumonia) because of linezolid's ability to inhibit bacterial toxin production.Ceftaroline is a potential alternative for the treatment of MRSA pneumonia but is not US Food and Drug Administration approved.

PREVENTION:

The three primary pillars for the prevention of CAP are:

●Smoking cessation (when appropriate)

●Influenza vaccination for all patients

●Pneumococcal vaccination for at-risk patients