Pneumonia

Pneumonia is a respiratory infection characterized by inflammation of the alveolar space and/or the interstitial tissue of the lungs. In industrialized nations, it is the leading infectious cause of death. Pneumonia is commonly transmitted via aspiration of airborne pathogens (primarily bacteria) but may also result from the aspiration of stomach contents. The spectrum of causal pathogens is mainly determined by patient age, immune status, and where the infection was acquired (community-acquired or hospital-acquired). Pneumonia is also classified based on clinical features as either typical and atypical; each type has its own spectrum of commonly associated pathogens. Typical pneumonia presents with sudden onset of malaise, fever, and a productive cough. On auscultation, crackles and bronchial breath sounds are audible. Atypical pneumonia, on the other hand, presents with gradual onset of unproductive cough, dyspnea, and extrapulmonary manifestations. Auscultation is typically unremarkable. In reality, some patients may present with elements of both types. Diagnostics include blood tests for inflammatory parameters and pathogen detection in blood, urine, or sputum samples. Chest x-ray in cases of typical pneumonia shows extensive opacity restricted to one lobe, while atypical pneumonia presents with diffuse, often subtle infiltrates. A newly developed pulmonary infiltrate on chest x-ray in combination with the clinical features confirms the diagnosis. Management consists of supportive measures, such as oxygen administration or physiotherapy, and antibiotic treatment. Antibiotics are initially administered empirically and later adapted based on the results of bacterial culture.

• Primary pneumonia: no apparent preexisting conditions that may predispose to pneumonia
• Secondary pneumonia
  • Bronchial asthma, COPD, heart failure, cystic fibrosis
  • Viral upper respiratory tract infections with bacterial superinfection
  • Anatomical abnormalities such as tubercular caverns, bronchial tumors, or stenosis (post-obstructive pneumonia)
  • Aspiration (aspiration pneumonia)
• Community-acquired pneumonia: (CAP: ): pneumonia that is acquired outside of a health care establishment
• Hospital-acquired pneumonia: (HAP: ): nosocomial pneumonia, with onset > 48 hours after admission
• Typical pneumonia
  • Pneumonia featuring classic symptoms (see “Clinical features” below); typical findings on auscultation and percussion
  • Manifests as lobar pneumonia or bronchopneumonia
• Atypical pneumonia
  • Pneumonia with less distinct classical symptoms and often unremarkable findings on auscultation and percussion
  • Manifests as interstitial pneumonia

References:^[1][2]

Pathogens

Type of pneumonia		Common pathogens
Community-acquired pneumonia	Typical pneumonia	Streptococcus pneumoniae (most common) Most common also in nursing home patients Haemophilus influenzae
	Atypical pneumonia	Mycoplasma pneumoniae (most common in the ambulatory setting) Chlamydophila pneumoniae Legionella pneumophila → legionellosis Coxiella burnetii
Hospital-acquired pneumonia		Gram-negative pathogens Pseudomonas aeruginosa Enterobacteriaceae Staphylococci (Staphylococcus aureus) Streptococcus pneumoniae
Special groups
Pneumonia in immunocompromised patients		Encapsulated bacteria Pneumocystis jirovecii → Pneumocystis jirovecii pneumonia Aspergillus fumigatus → aspergillosis Candida species → candidiasis Cytomegalovirus
Pneumonia in newborn infants		Escherichia coli Group B streptococcus (Streptococcus agalactiae) Streptococcus pneumoniae Haemophilus influenzae
Recurrent pneumonia		Unusual organisms (e.g., Nocardia, Coxiella burnetii, Aspergillus, Pseudomonas aeruginosa)

Routes of infection

• Most common: microaspiration (droplet infection) of airborne pathogens or oropharyngeal secretions
• Aspiration of gastric acid (Mendelson's syndrome) , or of food or liquids
• Hematogenous dissemination in rare cases

Risk factors

• Old age and immobility of any cause
• Chronic diseases
  • Preexisting cardiopulmonary conditions (e.g., bronchial asthma, COPD, heart failure)
  • Acquired or congenital abnormalities of the airways (e.g., bronchiectasis, space-occupying lesions, cystic fibrosis)
• Immunosuppression (e.g., HIV infection, diabetes mellitus, cytostatic therapy, alcoholism, immunosuppressive therapy)
• Smoking

References:^[3][4][5]

• Pulmonary protective mechanisms (cough reflex, mucociliary clearance , alveolar macrophages ) fail → microbial infiltration of the pulmonary parenchyma cannot be prevented
• Pathogen infiltrates pulmonary parenchyma → interstitial and alveolar inflammation → impaired alveolar ventilation → Ventilation/perfusion (V/Q) mismatch with intrapulmonary shunting (right to left) → hypoxia due to increased alveolar-arterial oxygen gradient (This effect is worsened if the affected lung is in the dependent position since perfusion is better to the dependent lung than the non-dependent lung)
• Pattern of involvement
  • Lobar pneumonia: classic (typical) pneumonia of an entire lobe, primarily caused by pneumococci
    • Classic disease progression in stages
      • Congestion (day 1): serous exudate in blood-rich lungs, numerous bacteria evident
      • Red hepatization (days 2–3): exudate rich in fibrin and inflammatory cells with many bacteria still visible; lungs take on a liver-like texture. Lung loses some spongy quality
      • Gray hepatization (days 4–7): erythrocytes are degraded but inflammatory cells persist; most bacteria have been destroyed by this stage; . Lung is now firm
      • Resolution (day 8 to week 4): fibrinolysis by enzymatic means and removal of the purulent exudate via productive cough
  • Bronchopneumonia: mostly descending infection that affects the bronchioles and adjacent alveoli; usually involves the lower lobes or right middle lobe; manifests as typical pneumonia
    • Primarily caused by pneumococci and/or other streptococci
    • Necrotizing bronchopneumonia (and pneumatocele) are caused by Staphylococcus aureus and are often preceded by an influenza infection.
  • Interstitial pneumonia: interstitial inflammation, particularly caused by mycoplasma and viral infections; manifests as atypical pneumonia
  • Miliary pneumonia: multiple small infiltrations caused by hematogenous dissemination (e.g., of tuberculosis)

References:^[6][7]

Typical pneumonia

Typical pneumonia presents with a sudden onset of symptoms caused by lobar infiltration.

• Severe malaise
• High fever and chills
• Productive cough with purulent sputum (yellow-greenish)
  • Crackles, bronchial, and decreased breath sounds on auscultation
  • Enhanced bronchophony, egophony, and tactile fremitus
  • Dullness on percussion
• Tachypnea and dyspnea (nasal flaring, thoracic retractions)
• Pleuritic chest pain when breathing, often accompanying pleural effusion
• Pain projecting to the abdomen and epigastric region (particularly in children)

Suspect bacterial pneumonia in immunocompromised patients with acute high fever and pleural effusion!

Atypical pneumonia

Atypical pneumonia typically takes an indolent course (slow onset) with an emphasis on extrapulmonary symptoms; . Common pathogens include mycoplasma, legionella, chlamydiae, and viruses such as RSV, influenza, CMV, and adenovirus.

• Low-grade fever
• Non-productive, dry cough
• Dyspnea
• Common extrapulmonary features include fatigue, headaches, sore throat, myalgias, malaise
• Auscultation often unremarkable

A clear distinction between typical and atypical pneumonia is not always possible based solely on the symptoms. As both forms may be caused by any pathogen, the distinction has little bearing on therapeutic decisions!

References:^{[8][9][6][10][11]}

Aspiration pneumonia

• Definition: Aspiration is the inhalation of foreign material into the respiratory tract. It often occurs after instrumentation of the upper airways or esophagus (e.g., upper GI endoscopy), or secondary to vomiting and regurgitation of gastric content.
  • Mendelson syndrome
    • Aspiration of gastric acid initially causing tracheobronchitis with rapid progression to chemical pneumonitis
    • May cause ARDS in extreme cases
• Risk factors
  • Altered consciousness: alcohol, sedation, general anesthesia
  • Apoplexy and neurodegenerative conditions
  • Gastroesophageal reflux disease, esophageal motility disorders
• Pathogens: mixed infections with anaerobic organisms are common (e.g., Klebsiella)
• Clinical findings
  • Immediate symptoms: bronchospasms ; , crackles on auscultation, hypoxemia with cyanosis
  • Late symptoms: fever, shortness of breath, cough with foul-smelling sputum
• Diagnosis
  • Radiologic imaging: infiltrates visible in lung regions according to body position on aspiration; (posterior upper lobes if recumbent, lower lobes if standing, often the lower right lobe due to the right bronchus' steep angle)
  • Arterial blood gas analysis (↓ PaO₂, pH < 7.35, PaCO₂ > 45 mm Hg)
• Management
  • Immediate (re)intubation with administration of 100% O₂
  • Endotracheal suction with microbiological analysis of bronchial secretions
  • Antibiotic treatment that covers anaerobes (e.g., clindamycin)
  • Regular monitoring: arterial blood gas, radiologic imaging
• Prevention: optimize therapy and/or prophylaxis of underlying causes to reduce the risk of aspiration

Pathogen-specific pneumonia

• Mycoplasma pneumonia:
  • Epidemiology
    • One of the most common causes of atypical pneumonia
    • More common in young individuals
    • Outbreaks may occur in schools, colleges, prisons, and military facilities
  • Clinical features
    • See atypical pneumonia
    • Generalized papular rash, erythema multiforme
  • Diagnostics
    • Subclinical hemolytic anemia: associated with elevated cold agglutinin titers (IgM)
    • Interstitial pneumonia, often with reticulonodular pattern on CXR
  • Treatment: macrolides, doxycycline, and fluoroquinolones
• Legionnaires’ disease
• Pneumocystis pneumonia
• Tuberculosis
• Primary influenza pneumonia
• Various viral infections (e.g., respiratory-syncytial-virus, hantavirus, adenovirus, CMV)
• SARS
• Ornithosis
• Pseudomonas aeruginosa: causes ventilator associated pneumonia

Lung abscess

• Definition: a localized collection of pus and necrotic tissue within lung parenchyma caused by microbial infection
• Risk factors
  • Predisposition to aspiration due to: reduced level of consciousness , dysphagia
  • Bronchial obstruction: lung cancer, foreign body aspiration, bronchial stenosis
  • Immunocompromised state
• Pathogens
  • Most commonly: mixed infections caused by anaerobic bacteria that colonize the oral cavity (e.g., Peptostreptococcus, Prevotella, Bacteroides, Fusobacterium spp.)
  • Less commonly: monomicrobial lung abscess caused by S. aureus, Klebsiella pneumoniae, Streptococcus pyogenes, Streptococcus anginosus
• Clinical findings: indolent presentation with symptoms that evolve over weeks to months
  • Fever
  • Cough with production of foul-smelling sputum
  • Anorexia, weight loss
  • Night sweats
  • Hemoptysis
• Diagnosis
  • Gram stain, culture, and sensitivity of expectorated sputum
  • Radiologic imaging (x-ray or CT): irregular rounded cavity with an air-fluid level in lung region on aspiration that is dependent on body position
• Management
  • Antibiotic treatment that covers anaerobes; (e.g., clindamycin, ampicillin-sulbactam, carbapenems)
  • If medical therapy fails, percutaneous catheter drainage or surgical resection may be considered.

References:^[12][13][14]

Laboratory tests

• Blood
  • ↑ CRP, ↑ ESR, leukocytosis, ↑ procalcitonin (PCT)
  • ABG to rule out respiratory failure ( ↓ PaO₂, pH < 7.35, PaCO₂ > 45 mm Hg)
• Pathogen detection
  • Blood cultures are always recommended.
  • Urine
    • Legionella antigen detection (if legionellosis is suspected)
    • Urine pneumococcal antigen test (if Streptococcus pneumoniae is suspected)
  • PCR and antibody tests to detect Chlamydia pneumoniae

Imaging

• Chest x-ray
  • Lobar pneumonia: extensive opacity restricted to one pulmonary lobe; positive air bronchogram ; unilateral pleural effusion may be visible
  • Bronchopneumonia: poorly defined patchy infiltrates scattered throughout the lungs, air bronchogram is unusual
  • Atypical or interstitial pneumonia: diffuse reticular opacity, absent (or minimal) consolidation

A newly developed pulmonary infiltrate on chest x-ray in a patient with the classic symptoms of pneumonia confirms the diagnosis!

• Thorax CT
  • Indications: inconclusive chest x-ray, recurrent pneumonia
  • Advantages: more reliable evaluation of circumscribed opacities, pleural emphysema, or sites of colliquation

Typical pneumonia usually appears as a lobar pneumonia on x-ray, while atypical pneumonia tends to appear as interstitial pneumonia. However, the underlying pathogen cannot be conclusively identified based on the imaging results!

Further diagnostics

The following tests are not part of the initial diagnostic workup; they are predominantly used for further investigation if the results of previous tests are negative or inconclusive.

• Sputum : testing for multiresistant pathogens ; severe, rapid progressive nosocomial pneumonia
• Pleurocentesis
  • pH metry value (normally 7.60–7.64)
  • Leukocyte count > 1000 WBCs/mm³ and protein levels (> 1-2 g/dL)
  • Inoculation of blood cultures with the puncture fluid and subsequent analysis
• Bronchoscopy: indicated to visualize and biopsy a central mass discovered on CT imaging, or if CT results are inconclusive

References:^{[15][16][6][4]}

Criteria for hospitalization

• Based on CURB-65 score (or CRB-65 score (without U) if it is not possible to measure urea)
  • Confusion (disorientation, impaired consciousness)
  • Urea > 7 mmol/L (20 mg/dL)
  • Respiratory rate ≥ 30/min
  • Blood pressure: systolic BP ≤ 90 mm Hg or diastolic BP ≤ 60 mm Hg
  • Age ≥ 65 years
  • Interpretation
    • Each finding is appointed 1 point; max. 5 points possible
    • CURB-65 score ≤ 1: The patient may be treated as an outpatient.
      • A patient with a CRB-65 score of 0 may be treated as an outpatient.
    • CURB-65 score ≥ 2: Hospitalization is indicated.
      • A patient with a CRB-65 score ≥ 1 should be admitted for hospital treatment.
    • CURB-65 score ≥ 3: ICU-care should be considered.

Any patient being treated in a primary care setting should be reexamined after 48–72 hours to evaluate the efficacy of the prescribed antibiotic!

General measures

• Sufficient rest (not absolute bedrest) and physical therapy
• High liquid intake (prevents dehydration, reduces bronchial secretion viscosity)
• Pulse oximetry monitoring
• Oxygen via nasal tube in cases of hypoxia
• Antipyretics, analgesics (e.g., acetaminophen, ibuprofen)
• Expectorants and mucolytics
• Antitussives (e.g., codeine)

Medical treatment of pneumonia

As laboratory results with definite pathogen identification may take time to obtain, initial empiric antibiotic treatment with broad coverage is recommended.

Community-acquired pneumonia
Treatment parameters		Regimen
Outpatient treatment	Patients without risk factors	Macrolide (e.g., azithromycin, clarithromycin, erythromycin ) OR doxycycline
	Patients with risk factors Recent antibiotic treatment Preexisting neurological conditions or diseases of internal organs (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, malignancy, asplenia, immunosuppression, alcoholism) Living in nursing homes	A 3rd or 4th generation respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin, gemifloxacin ) OR an antipneumococcal beta-lactam (e.g., amoxicillin ± clavulanate, ceftriaxone, cefpodoxime, cefuroxime) + macrolide (OR doxycycline)
Inpatient treatment	Non-ICU treatment	Respiratory fluoroquinolone OR an antipneumococcal beta-lactam (e.g., cefotaxime, ceftriaxone, ampicillin/sulbactam) + macrolide (OR doxycycline)
	ICU treatment for Acute respiratory failure Septic shock Decompensation of comorbidities (e.g., cardial decompensation, exacerbation of COPD, acute renal failure)	An antipneumococcal beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) + azithromycin OR + a respiratory fluoroquinolone If penicillin allergy: respiratory fluoroquinolone plus aztreonam
Special cases	If Pseudomonas aeruginosa is suspected	Antipneumococcal, antipseudomonal beta-lactam (piperacillin/tazobactam, cefepime, meropenem, or imipenem) + respiratory fluoroquinolone ± an aminoglycoside OR + azithromycin + aminoglycoside
	If MRSA is suspected	Add vancomycin or linezolid

Antibiotic treatment may be terminated 2–3 days after the fever subsides. In cases of community-acquired pneumonia that can be treated in the outpatient setting, seven days of antibiotic treatment are usually sufficient!

Hospital-acquired pneumonia

Hospital-acquired pneumonia
Profiles	Regimen
Patients without risk factors for multiresistant pathogens	An antipneumococcal beta-lactam (e.g., cefotaxime, ceftriaxone, amoxicillin/clavulanate) OR a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin)
Patients with risk factors for multiresistant pathogens Prior antibiotic treatment Hospitalization (on ICU) > 4 days Invasive ventilation > 4–6 days Colonization with multiresistant pathogens Structural lung disease Malnutrition	An antipneumococcal, antipseudomonal beta-lactam (piperacillin/tazobactam, cefepime, meropenem, or imipenem) If necessary, combination therapy with respiratory fluoroquinolone Alternatively, combination therapy with aminoglycoside (e.g., gentamicin)

Hospital-acquired pneumonia
Treatment parameters			Regimen
Low/moderate risk of mortality	Patients without risk factors for multiresistant pathogens		An antipneumococcal, antipseudomonal beta-lactam (e.g., piperacillin-tazobactam, cefepime, meropenem, or imipenem) OR a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin)
	Patients with risk factors for multiresistant pathogens*		An antipneumococcal, antipseudomonal beta-lactam (piperacillin/tazobactam, cefepime, meropenem, or imipenem) OR a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin) OR aztreonam + vancomycin OR linezolid
High risk of mortality or history of recent IV antibiotic use (< 90 days)			Two of the following (avoid 2 beta-lactams) An antipneumococcal, antipseudomonal beta-lactam (piperacillin/tazobactam, cefepime, meropenem, or imipenem) A respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin) An aminoglycoside (e.g., amikacin, gentamicin, tobramycin) Aztreonam + vancomycin OR linezolid
* Risk factors include: recent IV antibiotic treatment; hospitalization (on ICU); colonization with multiresistant pathogens; structural lung disease

References:^{[17][18][19][20][21][22][23]}

• Parapneumonic pleuritis
  • Fibrinous pleuritis: inflammation → increased vessel permeability → fibrin-rich exudate deposited on the serosal surface of the pleura
    • May present with pleuritic chest pain; , friction rub present
• Parapneumonic pleural effusion (common)
• Pleural empyema
• Sepsis
• Respiratory failure, ARDS

References:^[24][25][26]

We list the most important complications. The selection is not exhaustive.