2 Icahn School of Medicine at Mount Sinai, New York, NY, USA
Pneumonia is an infection of the lower respiratory tract due to bacteria, viruses, or less commonly fungal organisms.
Disease severity ranges from mild outpatient illness to severe infection with respiratory failure and sepsis, requiring admission to the ICU.
Community‐acquired pneumonia (CAP) is an acute infection of the lower respiratory tract acquired in the community, without hospitalization or regular exposure to health care facilities. Severe CAP is defined as requiring ICU management for shock, organ dysfunction, or mechanical ventilation.
Nosocomial pneumonia can be subdivided into hospital‐acquired pneumonia (HAP), pneumonia that develops after 48 hours of hospitalization, and health care‐associated pneumonia (HCAP). It occurs in patients with extensive health care contact and at risk for multidrug‐resistant (MDR) pathogens. Risks for HCAP include recent hospitalization >2 days in the past 90 days, contact with health care facilities (e.g. nursing home residence, hemodialysis center), recent antibiotic use, home wound care or infusion therapy, immunosuppression (e.g. corticosteroid use), or structural lung disease (e.g. bronchiectasis).
Ventilator‐associated pneumonia (VAP) is a type of HAP that develops after 48 hours of invasive mechanical ventilation. In 2013, the US Center for Disease Control and Prevention (CDC) recognized that the definition of VAP was neither sensitive nor specific. The CDC introduced the new concept of ventilator‐associated events (VAEs), a tiered surveillance definition. See also Chapter 44.
Ventilator‐associated condition (VAC): worsening oxygenation (increase in FiO2 ≥0.2 or PEEP ≥3 cmH2O) for ≥2 days following a period of stability.
Infection‐related ventilator‐associated complication (IVAC): VAC with fever or hypothermia, and/or leukocytosis or leukopenia, and receiving new antibiotics for ≥4 days.
Possible VAP: IVAC with purulent respiratory secretions with Gram stain evidence of respiratory infection or growth of a pathogen from respiratory cultures.
Probable VAP: Gram stain evidence of infection plus significant growth of a pathogenic organism from endotracheal aspirate, bronchoalveolar lavage (BAL), protected brush specimen, pleural fluid, or lung tissue; or detection of respiratory viruses or Legionella species.
The World Health Organization (WHO) estimates that lower respiratory tract infection is the most common infectious cause of death in the world, with almost 3.5 million deaths annually.
In the USA, the annual incidence of CAP requiring hospitalization is 25 cases per 10 000 adults, with the highest rates among those aged 65–79 years (nine times higher) and in those 80 years or older (25 times higher) as compared with those under 50 years of age.
HAP is the second most common nosocomial infection with a rate of 5–10 cases per 1000 adult patients.
Varies with the season and is dependent on the patient’s risk factors (see later in this chapter) and the setting in which pneumonia develops.
In a large study by the CDC, causative agents for CAP were found in only 38% of patients, with viruses detected in 27% and bacteria in 14% of patients.
Human rhinovirus and influenza are the most common viral pathogens isolated, followed by human metapneumovirus, respiratory syncytial virus, parainfluenza virus, coronavirus, and adenovirus.
Streptococcus pneumoniae is the most common bacterial cause of CAP, followed by Hemophilus influenza, and atypical pathogens such as Mycoplasma pneumoniae, Chlamydophila pneumoniae,and Legionella.
In patients with severe CAP, S. pneumoniae is most common, but Legionella, gram‐negative bacilli, Staphylococcus aureus, and influenza are important considerations.
Causes of nosocomial pneumonia tend to be more bacterial in nature, including methicillin‐sensitive Staphylococcus aureus (MSSA) and methicillin‐resistant Staphylococcus aureus (MRSA), Streptococcal spp., resistant gram‐negative organisms (Pseudomonas aeruginosa, Acinetobacter, Klebsiella, Enterobacter, Stenotrophomonas and Escherichia coli). Anaerobic pathogens have a minor role.
Viral and fungal pathogens should be considered in immunocompromised hosts. Pneumocystis jirovecii can cause pneumocystis pneumonia (PCP) in patients with acquired immune deficiency syndrome (AIDS) and those taking chronic corticosteroids.
Pneumonia develops when host defenses are overwhelmed by an infectious pathogen. This is typically a result of an inadequate immune response, often due to underlying comorbidities, immunosuppression, or from anatomic abnormalities (e.g. endobronchial obstruction, bronchiectasis). Pneumonia also occurs when the host defense system is overwhelmed by a large inoculum of microorganisms (e.g. massive aspiration) or a particularly virulent organism.
The primary route of infection is by micro‐aspiration of oropharyngeal pathogens. Hospitalized patients become colonized with nosocomial organisms in as little as 48 hours. Thus, patients with impaired mentation (e.g. stroke, dementia, intoxication) are particularly at risk. Chronically ill patients may be colonized by pathogens, particularly gram‐negative bacteria, and develop pneumonia when the immune response is inadequate.
Other routes of entry include inhalation (viruses, Legionella, and Mycobacterium tuberculosis), hematogenous dissemination from extrapulmonary sites of infection (right‐sided endocarditis), and direct extension.
In mechanically ventilated patients, aspiration of oropharyngeal and gastrointestinal contents can lead to pneumonia. Additionally, water reservoirs and respiratory devices can serve as a source of pneumonia.
Predictive/risk factors for CAP
HIV and AIDS
History of pneumonia
Cerebrovascular disease, stroke, and dementia
Chronic cardiovascular disease
Chronic liver or kidney disease
Chronic lung disease (COPD, asthma)
Poor dental hygiene
Risk factors for specific pathogens that cause pneumonia
Penicillin‐resistant and drug‐resistant S. pneumoniae
Age >65 years Alcoholism Immune suppression Multiple medical comorbid conditions Beta‐lactam therapy within past 3 months Exposure to a child in daycare center
Enteric gram‐negative bacteria
Recent antibiotic therapy Residence in a nursing home Underlying cardiopulmonary disease Multiple medical comorbid conditions
Malnutrition Structural lung disease (bronchiectasis) Corticosteroid therapy (prednisone >10 mg/day) Broad spectrum antibiotic therapy for >7 days in the past month
There are no screening tools for pneumonia.
Identifying patients at risk for MDR pathogens is important for infection control.
Smoking cessation and abstinence from alcohol abuse can reduce the risk of pneumonia.
All individuals over the age of 65 years, and high risk persons should receive pneumococcal (PCV‐13 and PCV‐23) and annual influenza vaccination.
All patients hospitalized with a medical illness should be considered for pneumococcal and influenza vaccination.
Strategies to prevent nosocomial pneumonia include use of non‐invasive positive pressure ventilation (NPPV) when possible.
Preventive strategies for VAP are combined in ventilator bundles: limit sedation, daily interruption of sedation, daily ventilator weaning trials, early mobilization, head of the bed elevation >30°, and oral care with chlorhexidine.
Use of endotracheal tubes (ETTs) with subglottic secretion drainage ports can potentially reduce VAP, however this is not in widespread practice.
Change ventilator tubing only when visibly soiled.
Selective oral or digestive decontamination, silver coated ETT, and early tracheostomy remain controversial in preventing VAP.
Vaccination and cessation of tobacco and alcohol abuse.
Antibiotic stewardship programs and infection control measures, especially proper hand hygiene, prevent the emergence of MDR bacteria.
Known or previously undiagnosed cardiac disease. Patients present with weight gain, lower extremity edema, and orthopnea. Examination reveals basilar rales, cardiac gallop, jugular venous distension, and edema. Chest radiograph often shows airspace opacities and brain natriuretic peptide may be elevated
History of neurologic disease, sedative use, or vomiting. Clinical signs of pneumonia can be delayed up to 2–3 days following aspiration event
History of pulmonary malignancy, weight loss, or aspiration of foreign body. Exam may reveal unilateral wheezing. Chest radiograph can show mass‐like consolidation, atelectasis, or unresolving pneumonia
Acute presentation with dyspnea, pleurisy, and hemoptysis. Chest radiographs can show wedge‐shaped opacities or sharp cutoffs of pulmonary vessels and CT angiogram confirms pulmonary embolism
Acute exacerbation of chronic lung disease (COPD, bronchiectasis, fibrosis)
Acute dyspnea, wheezing, and/or productive cough. Examination and imaging can mimic pneumonia
Acute respiratory distress syndrome
Acute dyspnea secondary to lung injury from pulmonary or non‐pulmonary insult. Hypoxemia and crackles often present. Chest imaging shows acute, bilateral alveolar–interstitial opacities
Cryptogenic organizing pneumonia
Recurrent pneumonia with fleeting opacities. Tissue diagnosis and prompt initiation of corticosteroid therapy are needed
Acute eosinophilic pneumonia
Presents like typical pneumonia, however does not resolve with antibiotics. Chest imaging may show peripheral opacities and BAL shows eosinophil‐predominant cell count. Lung biopsy confirms diagnosis
Idiopathic interstitial pneumonia
Interstitial lung disease that can present like pneumonia with abnormal chest imaging. Lung biopsy often needed for diagnosis
Lung disease associated with connective tissue disease
History of autoimmune disease and may present with additional, non‐pulmonary findings. Chest imaging reveals interstitial or nodular opacities
Drug‐induced pulmonary toxicity
Use of medications known to cause pulmonary toxicity (e.g. methotrexate, nitrofurantoin, amiodarone). Chest imaging can show interstitial changes or ground glass opacities
Patients present with fever, cough with productive sputum, and dyspnea. Cough and fever are present in 80% of patients with pneumonia. Purulent sputum is commonly seen in bacterial pneumonia while watery sputum is often associated with atypical organisms. Pleurisy may be present and can be indicative of severe disease or parapneumonic effusion (PPE).
Non‐respiratory symptoms such as confusion or generalized weakness may be the initial presentation in the elderly.
Patients with Legionella pneumonia can present with confusion, diarrhea, and electrolyte abnormalities.
In patients undergoing mechanical ventilation for >48 hours, the diagnosis of VAE/VAP should be considered (see Definitions section).
Pneumonia can present in a subacute or acute manner, with symptoms such as cough, purulent or blood‐tinged sputum, dyspnea, pleurisy, fever, and chills.
Extrapulmonary symptoms such as confusion or diarrhea may be present.
Special attention should be paid to recent travel history and exposure to sick contacts. It is crucial to identify MDR risk factors such as alcoholism, malnutrition, immunosuppression, recent antibiotic use, exposure to children in day care or health care facilities, and medical comorbidities.
Duration of hospitalization or ventilator support guides the choice of antibiotics.
Abnormal vital signs include fever, hypothermia, tachycardia, tachypnea, and hypoxemia.
Crackles are auscultated over the involved lobes. Bronchial breath sounds, tactile fremitus, whispered pectoriloquy, and egophony are findings of consolidation.
Patients with pleural effusion have decreased tactile fremitus and dullness to percussion.
Useful clinical decision rules and calculators
Scoring systems are infrequently used in clinical practice but were designed to predict the severity of CAP and determine the optimal site of care.
The 2007 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) consensus guidelines recommend using the CURB‐65 score or pneumonia severity index (PSI) to guide the initial site of treatment for adults with CAP.
A person with a CURB‐65 score of 2 should be hospitalized and those with a score of ≥3 should be assessed for ICU admission. See http://www.mdcalc.com/curb‐65‐severity‐score‐community‐acquired‐pneumonia/.
The PSI risk class correlates directly with mortality rate. See http://www.mdcalc.com/psi‐port‐score‐pneumonia‐severity‐index‐adult‐cap/.
ATS/IDSA criteria for ICU admission for CAP
Major criteria (1 or more = ICU admit)
Minor criteria (3 or more = ICU admit)
Endotracheal intubation and mechanical ventilation
Basic laboratory testing includes: complete blood count (CBC), basic metabolic panel (BMP), lactic acid, and arterial blood gas (ABG).
Respiratory cultures can include sputum, tracheal aspirates, and samples obtained via bronchoscopy. Bronchoscopy may provide diagnostic value in patients unable to expectorate or those with treatment failure.
Blood cultures are positive in <15% of cases (S. pneumoniae most commonly isolated) and are standard tests for patients with sepsis.
Nasal swabs for viral infection during appropriate seasons, including rapid influenza assay and PCR.
Urinary antigens for Legionella and S. pneumoniae.
Procalcitonin is a biomarker used to support the diagnosis of bacterial pneumonia and guide antimicrobial therapy. Some algorithms call for withholding or discontinuing antibiotic therapy for levels <0.1 μg/L while administering antibiotics if >0.25 μg/L. Utilization is not yet widely accepted.
C‐reactive protein is elevated in bacterial pneumonia.
ATS/IDSA: 1 major criteria or 3 minor criteria – ICU admission.
Managing the hospitalized patient
Monitor for clinical improvement by assessing symptoms, fever curve, WBC count, oxygen saturation, and lactic acid levels.
If there is no improvement despite 48 hours of appropriate antibiotics, consider parapneumonic effusion, other infectious etiology, and broadening antibiotics.
Principles of antimicrobial therapy
Early and appropriate antibiotics are of utmost importance.
Close attention to the patient’s clinical status and need for ventilatory support.
Choice of antibiotics should be based on type of pneumonia, site of care (ICU versus non‐ICU), risks for MDR organisms, and local antibiogram.
Hospitalized patients are treated with empiric parenteral antibiotic therapy.
Switch from intravenous to oral antibiotic regimen can be considered based on clinical improvement.
Treatment regimens may be simplified when the pathogen has been identified by reliable microbiologic testing.
Duration of antibiotic therapy is based on type of pneumonia and patient’s clinical response.
CAP: 5–7 days for uncomplicated cases but severe cases may require longer courses. Assess for clinical stability for 48–72 hours before discontinuing antibiotics.
HAP/HCAP: 7–8 days of empiric or culture‐directed antibiotics (see Chapter 44).
VAP: broad spectrum antibiotics for 72 hours, and then de‐escalation based on culture data and clinical response.
De‐escalation of antibiotics and shorter courses have been shown to improve outcomes.
Longer courses should be reserved for patients with delayed clinical response or those with Pseudomonas, Acinetobacter, S. aureus, or Legionella pneumonia.
Legionella pneumonia requires 10–14 days of therapy; up to 21 days in the immunosuppressed. Although macrolides and respiratory fluoroquinolones are both effective, more rapid defervescence, fewer complications, and shorter hospital stay are seen with fluoroquinolone therapy.
Procalcitonin‐guided algorithms may be effective in safely reducing the duration of antibiotics for CAP. However point‐of‐care testing is not available at all institutions.
Adjunctive aerosolized antibiotics can achieve higher concentrations in the lung than certain systemic antibiotics. Aerosolized antibiotics such as tobramycin, amikacin, and colistin have been used in VAP patients who are not responding despite appropriate systemic therapy or are infected with highly resistant organisms.
Failure to respond to initial antibiotic therapy should prompt consideration for broader antibiotic coverage, antifungal therapy, or additional imaging.
Antipneumococcal beta‐lactam plus macrolide or tetracycline:
Ceftriaxone 1–2 g daily, cefotaxime 1–2 g daily, or ampicillin‐sulbactam 1.5–3 g q6 h
Azithromycin 500 mg daily, clarithromycin 500 mg
q12 h, or doxycycline 100 mg q12 h
Severe CAP – ICU
Third‐generation cephalosporin plus macrolide (preferred) or tetracycline (alternative):
Ceftriaxone 2 g daily plus azithromycin 500 mg daily (preferred) or doxycycline 100 mg q12 h
Third‐generation cephalosporin plus respiratory fluoroquinolone:
Ceftriaxone 2 g daily plus either levofloxacin 750 mg or moxifloxacin 400 mg daily
Oseltamivir 75 mg twice a day × 5 days
Levofloxacin 750 mg or moxifloxacin 400 mg daily
Azithromycin 500 mg daily
Methylprednisolone 0.5 mg/kg q12 h × 5 days or prednisone 50 mg daily × 7 days
Choice of antibiotics should be individualized and based on local antibiogram Narrow antibiotics based on culture and susceptibility data Monotherapy with respiratory fluoroquinolone is sufficient in non‐severe CAP Cover atypical organisms with fluoroquinolone, macrolide, or tetracycline Combination therapy with macrolides shown to decrease mortality in CAP Doxycycline can be alternative to macrolide if QTc interval is prolonged. Dual therapy superior to monotherapy in critically ill patients with severe CAP and shock
Vancomycin 15 mg/kg IV q12 h
Linezolid 600 mg IV q12 h
Antipseudomonal, gram‐negative pathogens:
Beta‐lactam: piperacillin‐tazobactam 4.5 g q6 h
Cephalosporins: cefepime 1–2 g IV q8–12 h or ceftazidime 2 g IV q8 h
Carbapenem: imipenem 500 mg IV q6 h or 1 g q8 h, or meropenem 1 g IV qh
Aminoglycoside: gentamicin or tobramycin 7 mg/kg/day IV, amikacin 20 mg/kg/day
Fluoroquinolone: ciprofloxacin 400 mg q8 h or levofloxacin 750 mg daily
MRSA pneumonia should be considered in influenza cases Linezolid shown to have less treatment failure in MRSA pneumonia Aminoglycoside penetration into the lung and pleura is suboptimal; close monitoring of levels are essential Aerosolized antibiotics can be considered for resistant organisms
Multidisciplinary management to determine chest tube versus surgical management of complicated PPE and empyema Bronchoscopy can be diagnostic and therapeutic for endobronchial obstruction by foreign body Stenting of mainstem bronchi can relieve obstruction in setting of malignancy and post‐obstructive pneumonia
Fluoroscopic, ultrasound, or CT‐guided drainage in appropriate cases Radiation therapy can be considered for malignancy‐related endobronchial obstruction
The use of adjunctive corticosteroids for CAP is currently controversial. Several studies have suggested improved clinical outcomes such as reductions in time to clinical stability, duration of illness, treatment failure, progression to ARDS, and need for mechanical ventilation. Further studies are needed before corticosteroids can be strongly recommended.
Further imaging is indicated to assess for complications of pneumonia such as lung necrosis, abscess formation, complicated parapneumonic effusion, or empyema.
Pleural effusions associated with pneumonia should be sampled and drained.
Complicated PPEs and empyemas can be drained via tube thoracostomy with use of intrapleural tissue plasminogen activator (tPA) and DNase, or decorticated via video‐assisted thoracoscopy surgery (VATS) or thoracotomy.
Prevention/management of complications
Complications of pneumonia such as complicated PPE, empyema, lung necrosis, or abscess formation may develop.
Chest tube drainage or thoracic surgical intervention may be necessary for complicated pleuropulmonary infection.
Severe sepsis develops in almost 50% of patients with CAP; septic shock may be seen in 5% of CAP patients.
CAP is the most common cause of ARDS. Lung protective ventilation can prevent the development of ARDS.