History

• Fever may be reported ^c1
• Chills, sweating, and/or shivering ^c2c3c4
• Chest pain with inspiration and coughing ^c5c6c7c8
• Cough (productive or nonproductive) ^c9c10
• Dyspnea ^c11
• Fatigue ^c12
• Myalgia ^c13

Physical examination

• General
  • Altered mental status may occur with severe pneumonia, especially in the elderly ^c14c15
  • Fever (typically over 38.1°C) ^c16
  • Cyanosis, if hypoxemic ^c17
  • Tachypnea is a suggestive sign ^c18c19
  • Tachycardia occurs with fever and with severe disease ^c20
• Pulmonary
  • Respiratory splinting ^c21
  • Palpable fremitus ^c22
  • Dullness to percussion ^c23
  • Bronchial breath sounds or rales ^r3c24c25
  • Egophony ^c26
  • Whispered pectoriloquy ^c27

Causes

• Common pathogens ^r6r7
  • Streptococcus pneumoniae (pneumococcus) ^c28
  • Mycoplasma pneumoniae^c29
  • Haemophilus influenzae^c30
  • Chlamydia pneumoniae^c31
  • Staphylococcus aureus^c32
  • Legionella species ^c33
  • Gram-negative bacilli ^c34
  • MRSA ^c35
  • Pseudomonas aeruginosa^c36
  • Respiratory viruses ^c37
    • Influenza A and B viruses ^c38c39
    • Parainfluenza virus ^c40
    • Respiratory syncytial virus ^c41
    • Adenoviruses ^c42
    • Rhinovirus ^c43
    • Coronavirus ^c44

Risk factors and/or associations

Primary diagnostic tools

• History and physical examination alone may be sufficient to suggest the diagnosis ^r7c69
• Chest radiography or other chest imaging demonstrating an infiltrate confirms the diagnosis ^r7
• Testing to identify a causative agent is not routine for outpatients ^r7
• Testing to identify a causative agent (eg, blood cultures, sputum testing, pleural fluid testing, urinary antigen testing, and/or cultures for fungi and tuberculosis, depending on history and clinical findings) is indicated if: ^r7
  • Severe pneumonia
  • Pleural effusion and/or a cavitary infiltrate
  • Specific comorbidities (eg, alcohol use disorder, liver disease, leukopenia, chronic lung disease, asplenia)
  • Identification of a suspected pathogen would significantly alter antibiotic choice
  • Failure of outpatient treatment
  • Epidemiologic considerations (eg, outbreaks of public health importance)
• Pulse oximetry assesses hypoxemia ^r7c70
• Other laboratory tests—including blood gases, CBC, C-reactive protein, and blood chemistries (including lactate)—may be useful in both determining degree of severity at presentation and managing hospitalized patients ^r7
• Serum procalcitonin has been used to discriminate between infectious and noninfectious causes of pneumonia and between bacterial and viral causes. However, current guidelines do not recommend its use either to determine need for antibacterial therapy or to determine when to discontinue antibiotics ^r3r8

Laboratory

• Blood gas tests are not routine, but they are indicated when there is respiratory distress and/or suspicion of carbon dioxide retention ^c71c72
  • PaO₂ or FiO₂ ratio less than 250 suggests the need for ICU admission and/or mechanical ventilation ^r9
• CBC will reveal leukocytosis in most cases of community-acquired pneumonia ^c73
  • Leukopenia (WBC count less than 4000) suggests immunosuppression or severe infection and the need for hospitalization ^r9
  • Thrombocytopenia (platelet count less than 100,000 cells/mm³) may be present and is associated with poor prognosis ^r7
• Serum chemistry testing is indicated for hospitalized patients receiving IV fluids and to monitor renal function and glucose levels in patients with severe pneumonia. BUN level can be used as a criterion to determine a CURB-65 score. Lactate level^r11 can be used to identify and manage sepsis ^r10c74
• C-reactive protein
  • C-reactive protein level greater than 30 mg/L, in addition to suggestive symptoms and signs, implies diagnosis of pneumonia ^r8
• Etiologic testing
  • Blood cultures are indicated for patients with: ^r3
    • Severe community-acquired pneumonia (patients admitted to ICU) ^c75
    • Patients being empirically treated for MRSA or Pseudomonas aeruginosa (or other resistant gram-negative bacilli)
    • Patients previously infected with MRSA or Pseudomonas aeruginosa (or other resistant gram-negative bacilli), especially those with history of respiratory tract infection
    • Patients who were hospitalized and received parenteral antibiotics, whether during the hospitalization event or not, in the last 90 days
  • Sputum Gram stain and culture are indicated for: ^r3
    • All ICU patients (severe) ^c76c77
      • Use an endotracheal specimen in intubated patients
    • Patients being empirically treated for MRSA or Pseudomonas aeruginosa (or other resistant gram-negative bacilli)
    • Patients previously infected with MRSA or Pseudomonas aeruginosa (or other resistant gram-negative bacilli), especially those with prior respiratory tract infection
    • Patients who were hospitalized and received parenteral antibiotics, whether during the hospitalization event or not, within the last 90 days
• Pathogen-specific tests
  • Legionella urinary antigen test
    • Indicated for patients with any of the following: ^r3
      • Severe community-acquired pneumonia ^c78
      • In cases where indicated by epidemiologic factors, such as association with a Legionella outbreak or recent travel
  • Pneumococcal urinary antigen test (for diagnosis of Streptococcus pneumoniae)
    • Indicated only for patients with: ^r3
      • Severe community-acquired pneumonia ^c79
  • Influenza test ^r3
    • Obtain nasal swab samples to test for influenza in patients with suspected viral pneumonia ^r12c80c81
    • Testing for influenza with a rapid influenza molecular assay (ie, influenza nucleic acid amplification test) is preferred over a rapid influenza diagnostic test (ie, antigen test) ^r3
    • Standard polymerase chain reaction test may be used if rapid molecular test is not available. It detects influenza A and B viruses on sputum and endotracheal or bronchoalveolar lavage specimens and confirms positive nasal swab rapid test result in nonepidemic settings ^r13c82c83
  • Fungal culture and tuberculosis testing
    • Indicated for patients with:
      • Cavitary infiltrate on chest radiograph ^r7c84c85
      • Persistent cough associated with weight loss, weakness, or night sweats ^r12c86c87
      • Presence of risk factors for tuberculosis (eg, older adults, those who traveled to or reside in tuberculosis-endemic regions, those with low socioeconomic status) ^{r12c88c89c90c91c92c93}
  • Serology and/or polymerase chain reaction test may be indicated to confirm the diagnosis of pathogens such as Chlamydia, Legionella, or Mycoplasma pneumoniae^{r12c94c95c96c97c98c99}

Imaging

• Chest radiography ^r7c100
  • Routine investigation for evaluation of pneumonia in adults
  • Results may be negative, especially with dehydration
  • Lung infiltrate is the hallmark finding
  • May demonstrate alveolar filling with inflammatory exudate or interstitial thickening
  • Pleural effusion may be present
• Lung ultrasonography ^r14r15c101
  • Accurate alternative to chest radiography that may be performed at bedside in emergency department setting or in critically ill patients ^r16r17
  • May be used as adjunctive means of diagnosing pneumonia, especially in patients with baseline chest radiograph abnormalities
• CT ^r16c102
  • More sensitive than plain radiographs for detecting pneumonia
  • Consider if clinical suspicion for pneumonia remains high despite negative chest radiography findings
  • Better at visualizing upper lobes and lingula, necrotizing infection, multilobar disease, interstitial infiltrates due to atypical pathogens, empyema, and pleural involvement
  • Useful for excluding tuberculosis or lung cancer

Procedures

Most common

• Bronchitis ^c105d1
  • Presents with fever, malaise, productive cough, hoarseness, chest pain, and muscle pain
  • Differentiated by chest radiography and physical examination
    • No radiographic evidence of pulmonary pathology
    • Signs of consolidation (eg, rales, egophony, fremitus) indicative of pneumonia will be absent
• Seasonal influenza ^c106d2
  • Sudden onset of high fever with chills, myalgia, or malaise
  • Dry cough, sneezing, sore throat, nasal discharge, and substernal soreness
  • History of contact with an infected person
  • Viral infection present in the winter season
  • Differentiated by history and laboratory testing
    • Antigen detection test using nasopharyngeal secretion will help in detecting type A and type B viral antigens
• Asthma ^d3
  • Patient may present with recurrent attacks of dyspnea with wheezing or accessory muscle use ^c107
  • Differentiated by history (absence of fever), chest radiography, spirometry/pulmonary function testing, and response to bronchodilators
• Chronic obstructive pulmonary disease ^c108d4
  • Patients present with dyspnea, pursed lip breathing, or use of accessory muscles for breathing
  • Other features include chronic productive cough, cyanosis, tachycardia, and tachypnea
  • Differentiated by history, chest radiography, and spirometry/pulmonary function testing
    • Spirometry shows abnormal diffusing capacity, fixed reduction in FEV1, and increased total lung capacity and/or residual volume in patients with chronic obstructive pulmonary disease
    • Chest radiography shows hyperinflation with flattened diaphragm, tenting of the diaphragm at the rib, and increased retrosternal chest space in patients with chronic obstructive pulmonary disease
• Congestive heart failure ^d5
  • Characterized by: ^c109
    • Dyspnea
    • Fatigue
    • Exercise intolerance
    • Fluid retention
  • Differentiated by:
    • Chest radiography showing:
      • Pulmonary edema
      • Pleural effusion
      • Pulmonary venous congestion
      • Chamber dilation
      • Kerley B lines
      • Cardiomegaly
    • Echocardiography showing abnormalities with cardiac structure and function
• Pneumothorax
  • Sudden onset of breathlessness and chest pain ^c110
  • Differentiated by history, physical examination, and chest radiography
    • Chest radiography will reveal air in the pleural space
• Pulmonary embolism ^d6
  • Blocking of pulmonary artery by thrombus
  • Patients present with dyspnea and pleuritic chest pain but usually do not have a fever or cough productive of purulent sputum ^c111
  • Calf tenderness and swelling may be present if embolism was caused by deep venous thrombosis
  • Differentiated by history, physical examination, and imaging
    • Chest CT shows filling defects in the pulmonary arteries
• Tuberculosis ^d7
  • Patients present with weight loss, night sweats, and cough ^c112
  • Travel to or residence in a tuberculosis-infected endemic area or advanced age (born early 20th century during worldwide endemicity)
  • Differentiated by history, laboratory testing, and imaging
    • Positive tuberculin test result
    • Chest radiography findings of reactivation disease (usually in older patients) showing upper-lobe predominance or cavity, and/or granuloma formation
    • Chest radiography of primary tuberculous pneumonia (usually in in younger patients) showing hilar adenopathy, and/or pleural effusion (sometimes massive)

Admission criteria

Use severity of illness scores in combination with clinical judgment to determine if the patient can be safely managed as an outpatient or should be managed as an inpatient; 2019 guidelines recommend Pneumonia Severity Index preferentially over the CURB-65 criteria ^r3

• Pneumonia Severity Index ^r20
  • Uses a point system of several variables including patient age, vital signs, mental status, and the presence of comorbid conditions (eg, neoplastic disease, liver disease, chronic heart failure, cerebrovascular disease, renal disease)
  • Classifies patients into a mortality risk level
    • Class I and II patients (fewer than 70 points) may be treated as outpatients
    • Class III patients should be treated in an observation unit or briefly hospitalized (71-90 points)
    • Class IV (91-130 points) and V (greater than 130 points) should be treated as inpatients
• CURB-65 criteria ^r1
  • Patients receive 1 point for each of the following indicators:
    • Confusion (compared to baseline)
    • BUN greater than 20 mg/dL
    • Respiratory rate greater than or equal to 30 breaths per minute
    • Systolic blood pressure less than 90 mm Hg or diastolic blood pressure of 60 mm Hg or less
    • Age 65 years or older
  • Inpatient admission is recommended for patients with a score of 2 or more
  • Most patients with a score of 1 can be managed as outpatients; consider overnight observation for some patients
• Studies of specific biomarkers used to identify high-risk patients have not proven more accurate than these scoring systems ^r21

Consider inpatient admission for patients otherwise meeting criteria for outpatient treatment but who are unable to safely and reliably take medication orally or who have insufficient personal support ^r12

Recommendations for specialist referral

• Refer to pulmonologist for:
  • Respiratory failure requiring noninvasive and positive pressure ventilation or intubation and mechanical ventilation
  • Worsening hypoxemia
  • Pleural effusion requiring chest tube drainage
  • Nonresolving pneumonia (characterized by persistent fever and absence of clinical improvement)
  • Bronchoscopic sampling, if necessary
• Refer to infectious disease specialist for assistance with identification of causative agent and antibiotic management of severe pneumonia or pneumonia that does not respond to empiric antibiotics

Drug therapy

• Antibiotics ^r6
  • Macrolides ^c113
    • First line therapy for outpatient treatment; used in combination with other antibiotics in the inpatient setting
    • Azithromycin ^c114
      • Azithromycin Oral tablet; Outpatient Adults: 500 mg PO on day 1, followed by 250 mg PO once daily for at least 5 days.
      • Azithromycin Oral tablet; Hospitalized Adults: 500 mg PO once daily for at least 5 days.
      • Azithromycin Solution for injection; Adults: 500 mg IV once daily for at least 5 days.
    • Clarithromycin ^c115
      • Clarithromycin Oral tablet; Adults: 500 mg PO every 12 hours for at least 5 days.
  • Tetracyclines ^c116
    • Acceptable alternative to macrolides
    • Doxycycline ^c117
      • Doxycycline Hyclate Oral tablet; Adults: 100 mg PO every 12 hours for at least 5 days.
      • Doxycycline Hyclate Solution for injection; Adults: 100 mg IV every 12 hours for at least 5 days.
  • Quinolones ^c118
    • Respiratory quinolones (ie, gemifloxacin, moxifloxacin, levofloxacin, delafloxacin) are first line outpatient therapy for patients with community-acquired pneumonia who are at risk for multidrug-resistant Streptococcus pneumoniae
    • Gemifloxacin ^c119
      • Gemifloxacin Oral tablet; Adults: 320 mg PO once daily for at least 5 days.
    • Moxifloxacin ^c120
      • Moxifloxacin Hydrochloride Oral tablet; Adults: 400 mg PO once daily for at least 5 days.
      • Moxifloxacin Hydrochloride Solution for injection; Adults: 400 mg IV once daily for at least 5 days.
    • Levofloxacin ^c121c122
      • Levofloxacin Oral tablet; Adults: 750 mg PO every 24 hours for at least 5 days.
      • Levofloxacin Solution for injection; Adults: 750 mg IV every 24 hours for at least 5 days.
    • Delafloxacin ^r26c123
      • Delafloxacin Oral tablet; Adults: 450 mg PO every 12 hours for 5 to 10 days.
      • Delafloxacin Solution for injection; Adults: 300 mg IV every 12 hours for 5 to 10 days.
  • Penicillins ^c124c125
    • Frequently used in combination regimens in both outpatient and inpatient settings
    • Amoxicillin ^c126c127
      • Amoxicillin Trihydrate Oral tablet; Adults: 1 g PO every 8 hours for at least 5 days.
    • Amoxicillin-clavulanate ^c128c129
      • Amoxicillin Trihydrate, Clavulanate Potassium Oral tablet; Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for at least 5 days.
      • Amoxicillin Trihydrate, Clavulanate Potassium Oral tablet, extended-release; Adults: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for at least 5 days.
    • Ampicillin-sulbactam ^c130c131
      • Ampicillin Sodium, Sulbactam Sodium Solution for injection; Adults: 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for at least 5 days.
    • Piperacillin-tazobactam ^c132c133
      • Tazobactam Sodium, Piperacillin Sodium Solution for injection; Adults: 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours for at least 7 days.
  • Cephalosporins ^c134c135
    • Frequently used in combination regimens in both outpatient and inpatient settings
    • Cefuroxime ^c136c137
      • Cefuroxime Axetil Oral tablet; Adults: 500 mg PO every 12 hours for at least 5 days.
    • Cefpodoxime ^c138c139
      • Cefpodoxime Proxetil Oral tablet; Adults: 200 mg PO every 12 hours for at least 5 days.
    • Ceftriaxone ^c140c141
      • Ceftriaxone Sodium Solution for injection; Adults: 1 to 2 g IV every 24 hours for at least 5 days.
    • Cefotaxime ^c142c143
      • Cefotaxime Sodium Solution for injection; Adults: 1 to 2 g IV every 8 hours for at least 5 days.
    • Ceftaroline ^c144
      • Ceftaroline fosamil Solution for injection; Adults: 600 mg IV every 12 hours for at least 5 days.
    • Cefepime ^c145c146
      • Cefepime Hydrochloride Solution for injection; Adults: 2 g IV every 8 hours for at least 7 days.
    • Ceftazidime ^c147
      • Ceftazidime Sodium Solution for injection; Adults: 2 g IV every 8 hours for at least 7 days.
  • Carbapenems ^c148c149
    • Used in combination regimens in the inpatient and ICU settings to manage seriously ill patients with community-acquired pneumonia; imipenem-cilastatin and meropenem also provide coverage for suspected Pseudomonas infection
    • Imipenem-cilastatin ^c150c151
      • Imipenem, Cilastatin Sodium Solution for injection; Adults: 500 mg IV every 6 hours for at least 7 days.
    • Meropenem ^c152c153
      • Meropenem Solution for injection; Adults: 1 g IV every 8 hours for at least 7 days.
  • Monobactams ^c154c155
    • Used in combination regimens in the inpatient and ICU settings to manage seriously ill patients with community-acquired pneumonia who are allergic to penicillin
    • Aztreonam ^c156c157
      • Aztreonam Solution for injection; Adults: 2 g IV every 8 hours for at least 7 days.
  • Glycopeptides ^c158c159
    • Used for the treatment of MRSA and penicillin-resistant pneumococci
    • Vancomycin ^c160c161
      • Vancomycin Hydrochloride Solution for injection; Adults: 20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for at least 7 days.
  • Oxazolidinones ^c162c163
    • Used for the treatment of infections due to aerobic gram-positive bacteria, including MRSA and penicillin-resistant pneumococci
    • Linezolid ^c164c165
      • Linezolid Oral tablet; Adults: 600 mg PO every 12 hours for at least 7 days.
      • Linezolid Solution for injection; Adults: 600 mg IV every 12 hours for at least 7 days.
  • Pleuromutilin ^c166
    • Lefamulin ^r27c167
      • First-in-class antibiotic approved to treat community-acquired pneumonia
      • Lefamulin Oral tablet; Adults: 600 mg PO every 12 hours for 5 days.
      • Lefamulin Solution for injection; Adults: 150 mg IV every 12 hours for 5 to 7 days.
• Antiviral agents ^r6r28c168
  • Antiviral agents are recommended for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness; who are hospitalized; or who are at high risk for complications, regardless of the time since symptom onset. Can be considered for previously healthy, symptomatic outpatients not at high risk for influenza complications if initiated within 48 hours of onset of symptoms ^c169c170
  • Neuraminidase inhibitors ^c171
    • Oseltamivir ^c172
      • Oseltamivir Phosphate Oral capsule; Adults: 75 mg PO twice daily for 5 days.
    • Zanamivir ^c173
      • Zanamivir Inhalation powder; Adults: 10 mg by oral inhalation every 12 hours for 5 days.
    • Peramivir ^c174
      • Peramivir Solution for injection; Adults: 600 mg IV as a single dose.
  • Polymerase acidic endonuclease inhibitor
    • Baloxavir ^r29c175
      • Baloxavir Marboxil Oral tablet; Adults less than 80 kg: 40 mg PO as a single dose.
      • Baloxavir Marboxil Oral tablet; Adults weighing 80 kg or more: 80 mg PO as a single dose.

Nondrug and supportive care

Supplemental oxygen or mechanical ventilation ^r30

• May be required in patients with severe pneumonia or underlying cardiopulmonary disease ^c176c177c178
• Maintain oxygen saturation within 94% to 98% in patients with hypoxemia ^r22

Respiratory therapy ^c179

• Postural drainage facilitated by chest percussion may be helpful in patients who have difficulty mobilizing respiratory secretions ^c180c181

Breathing exercises ^c182

• Strengthen the chest wall muscles; beneficial particularly to sedentary patients
• Help patients mobilize secretions to improve expectoration

Venous thromboembolism prophylaxis ^r22c183

• Low-molecular-weight heparin is recommended in patients at high risk
• Early ambulation is recommended

Smoking cessation ^r31c184

• Advise patients to quit smoking, using counseling and pharmacologic approaches recommended in tobacco cessation guidelines and reviews ^r31r32d8

Comorbidities

• Patients with comorbid disorders such as neoplastic disease, liver disease, congestive heart failure, cerebrovascular disease, or renal disease are likely to require hospital admission and IV antibiotics, at least initially ^{c186c187c188c189c190}
• Immunocompromised patients ^c191
  • Prone to multiorganism pneumonia, including unusual pathogens such as cytomegalovirus, Pneumocystis jiroveci, and fungal infection
  • Microbiologic diagnosis may require bronchoscopy with biopsy, immunohistology, and quantitative molecular assays
  • Begin empiric therapy as soon as possible based on epidemiologic history, sputum Gram stain, previous courses of antimicrobial agents, and historical microbiologic data

Special populations

• Elderly patients
  • Classic signs and symptoms may be absent or altered in elderly patients
    • Presentation may include nonspecific symptoms such as confusion ^r12
  • May recover more slowly compared with younger patients
  • Aspiration is an important risk factor for community-acquired pneumonia in elderly patients
• Pregnant women
  • Prone to preterm labor and delivery
  • Prone to pulmonary edema
  • Acidosis and hypoxic state are poorly tolerated by the fetus
  • High risk for severe influenza
  • Treat with pregnancy-safe antibiotics
    • Azithromycin or erythromycin with or without ceftriaxone, depending on severity of illness; antiviral neuraminidase inhibitor for influenza
    • Antibiotics to be avoided in pregnancy include doxycycline, fluoroquinolones, and clarithromycin
    • Lefamulin may cause fetal harm when administered during pregnancy; effective contraception use is recommended for women of reproductive potential