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Jan.22.2021View related content

Community-acquired pneumonia in adults

Synopsis

Key Points

  • Community-acquired pneumonia is an acute infection of the pulmonary parenchyma that is not acquired in a hospital or other health care facility (patient not hospitalized nor residing in a long-term care facility for at least 14 days before the onset of symptoms)
  • History and physical examination suggest diagnosis, which is confirmed with chest radiography
  • Testing for the causative agent (eg, blood and sputum cultures) is not necessary for patients able to be treated as outpatients unless it is likely that treatment would change based on a suspected unusual pathogen
  • Base site of care decisions (eg, outpatient, general hospital ward, ICU) on pneumonia severity level, Pneumonia Severity Index score, and CURB-65r1 score. Do not allow these scoring systems to supersede clinical judgment
  • Select empiric antibiotic therapy based on the site of care and likely pathogen. Initiate treatment promptly once diagnosis of pneumonia appears likely
  • Patients able to be treated as outpatients with no significant risk of drug-resistant Streptococcus pneumoniae should receive first line therapy with a macrolide or second line therapy with doxycycline
  • Treat hospitalized (general ward) patients with no significant risk of drug-resistant Streptococcus pneumoniae empirically with respiratory quinolone monotherapy; alternatives include a β-lactam plus a macrolide or a β-lactam plus doxycycline
  • First line treatment for patients in ICU is usually a combination therapy of β-lactam plus either azithromycin or a respiratory quinolone
  • Additional coverage is required in patients with suspected community-acquired MRSA or Pseudomonas species infections
  • Treat all hospitalized patients who test positive for influenza with oseltamivir, regardless of the duration of illness
  • Pneumococcal vaccination is indicated in patients older than 65 years and in younger patients with chronic medical conditions; influenza vaccination is recommended for all persons aged 6 months and older

Urgent Action

  • In patients being admitted, initiate empiric antibiotic therapy as soon as possible, within 6 hours of presentation to the emergency department r2
  • Admit patients presenting with acute respiratory failure and septic shock directly to the ICU r3

Pitfalls

  • Lack of response to initial therapy may suggest unusual pathogens (eg, Legionella species, fungi, viruses), nosocomial infection, or an infectious complication (eg, empyema, postobstructive pneumonia, abscess)
  • False-negative chest radiograph findings may occur, especially in a dehydrated patient; the diagnosis should then primarily depend on history and physical examination findings
  • False-negative respiratory sample cultures can occur if obtained after antibiotic therapy has been started r4

Terminology

Clinical Clarification

  • Community-acquired pneumonia in adults is acute infection of the pulmonary parenchyma that is not acquired in a hospital or other health care facility (patient not hospitalized nor residing in a long-term care facility for at least 14 days before the onset of symptoms) r2

Classification

  • By cause r5
    • Typical
      • Classically caused by Streptococcus pneumoniae, but other pyogenic organisms may cause a similar presentation
      • Characterized both by cough that produces purulent sputum and by lobar consolidation
    • Atypical
      • Caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella species, and respiratory viruses
      • Characterized by dry cough and patchy infiltrates
  • By severity level (and site of care) r3
    • Determined by severity of illness scores in combination with clinical judgment and an assessment of the patient’s social support
      • Pneumonia that can be managed in an outpatient setting
      • Pneumonia that should be managed with inpatient admission (general ward)
      • Pneumonia that is severe and should be managed in the ICU
    • Severe community-acquired pneumonia (either major criteria or 3 or more minor criteria) r3
      • Major criteria
        • Need for mechanical ventilation
        • Septic shock with need for vasopressors
      • Minor criteria
        • Respiratory rate of 30 breaths per minute or more
        • Ratio of arterial partial pressure of oxygen (PaO₂) to fraction of inspired oxygen (FiO₂) 250 or less
        • Multilobar disease
        • Leukopenia (leukocyte count less than 4000 cells/μL)
        • Uremia (BUN level of 20 mg/dL or higher)
        • Confusion or disorientation
        • Hypothermia (core temperature lower than 36°C)
        • Thrombocytopenia (platelet count less than 100,000 cells/μL)
        • Hypotension requiring aggressive fluid resuscitation

Diagnosis

Clinical Presentation

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 and Risk Factors

Causes

  • Common pathogens r6r7
    • Streptococcus pneumoniae (pneumococcus) c28
    • Mycoplasma pneumoniaec29
    • Haemophilus influenzaec30
    • Chlamydia pneumoniaec31
    • Staphylococcus aureusc32
    • Legionella species c33
    • Gram-negative bacilli c34
    • MRSA c35
    • Pseudomonas aeruginosac36
    • 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

Other risk factors/associations
  • Hospitalization and treatment with parenteral antibiotics in the preceding 90 days c45
    • MRSA, Pseudomonas aeruginosa, resistant gram-negative bacilli
      • Documented history of infection with these organisms
      • Previously regarded as health care–associated pneumonia, infection due to these bacteria is now considered within the spectrum of community-acquired pneumonia r3
  • Chronic obstructive pulmonary disease c46
    • Streptococcus pneumoniae
    • Haemophilus influenzae
    • Moraxella (Branhamella) catarrhalis
    • Legionella species
  • Bronchiectasis c47
    • Pseudomonasaeruginosa
    • Burkholderia cepacia
    • Staphylococcus aureus
  • Cystic fibrosis c48
    • Pseudomonas aeruginosa
      • Most common organism in adults
  • Diabetes c49
    • Staphylococcus aureus
    • Gram-negative organisms
  • Renal disease c50
    • Streptococcus pneumoniae
  • Early-stage HIV c51
    • Streptococcus pneumoniae
    • Haemophilus influenzae
    • Mycobacterium tuberculosis
  • Late-stage HIV
    • Pneumocystisjiroveci
    • Cryptococcus species
    • Histoplasma species
  • Medical conditions that result in aspiration of nasopharyngeal secretions, food, liquids, or gastric contents c52
  • Alcohol use disorder c53
    • Streptococcus pneumoniae
    • Klebsiella pneumoniae
    • Anaerobic bacteria
  • Asplenia c54c55
    • Encapsulated organisms
      • Streptococcus pneumoniae
      • Haemophilus influenzae
  • Sickle cell disease c56
    • Streptococcus pneumonia
    • Haemophilus influenzae
  • Poor dental hygiene c57
    • Anaerobic bacteria
  • Smoking c58
    • Streptococcus pneumonia
    • Haemophilus influenzae
    • Moraxella (Branhamella) catarrhalis
    • Legionella species
  • Travel history c59
    • Travel to area of known outbreak within 2 weeks before illness c60
      • Legionella species
    • Travel to the southwestern United States within 1 month before illness c61
      • Coccidioides species
  • Exposure to animals c62
    • Exposure to bats or soil enriched with bird droppings c63c64
      • Histoplasma capsulatum
    • Exposure to birds c65
      • Chlamydia psittaci
    • Exposure to rabbits c66
      • Francisella tularensis
    • Exposure to farm animals or parturient cats c67c68
      • Coxiella burnetii

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination alone may be sufficient to suggest the diagnosis r6c69
  • Chest radiography or other chest imaging demonstrating an infiltrate confirms the diagnosis r6
  • Testing to identify a causative agent is not routine for outpatients r6
  • 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: r6
    • 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 r6c70
  • 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 r6
  • 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 r6
  • 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 levelr11 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 r6c84c85
        • 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 pneumoniaer12c94c95c96c97c98c99

Imaging

  • Chest radiography r6c100
    • 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 r17c102
    • 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

Diagnostic thoracentesis r6c103
General explanation
  • Insertion of a small-gauge needle between the ribs, through the thorax, and into the pleural space to access pleural fluid for diagnostic purposes
  • Procedure can be performed with or without ultrasonographic guidance
Indication
  • Pleural effusions greater than 5 cm high on a lateral view chest radiograph c104
Contraindications
  • No absolute contraindications
  • Relative
    • Uncorrected coagulopathy
    • Small effusion with secure clinical diagnosis
    • Mechanically ventilated patient
    • Perform bilateral thoracentesis only after ensuring absence of pneumothorax in the first side
Complications r18
  • Pain at puncture site
  • Bleeding (eg, hematoma, hemothorax, hemoperitoneum)
  • Pneumothorax
  • Re-expansion pulmonary edema
  • Infection (eg, empyema, soft tissue infection)
  • Spleen or liver puncture
  • Vasovagal events
  • Retained intrapleural catheter fragments
Interpretation of results
  • Pleural fluid analysis
    • Obtain pH, glucose, Gram stain, and aerobic and anaerobic cultures r19
      • Parapneumonic effusion and empyema are exudative
        • Protein level higher than 3 g/dL
        • Ratio of pleural fluid protein to serum protein greater than 0.5
        • Lactate dehydrogenase level higher than 200 units/L
        • Ratio of pleural fluid lactate dehydrogenase to serum lactate dehydrogenase higher than 0.6
        • Glucose level lower than 60 mg/mL
      • pH is generally low
      • WBC count may exceed 50,000 cells/mm³ with neutrophils predominating
    • Fluid can be saved for further analysis based on initial results
    • Other pleural fluid testing, such as cytology, based on clinical suspicion

Differential Diagnosis

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)

Treatment

Goals

  • Eradicate infection with antibiotics
  • Relieve symptoms and provide supportive care as needed
  • Prevent disease progression and complications

Disposition

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

Criteria for ICU admission
  • Recommended with either major criteria or 3 or more minor criteria (severe community-acquired pneumonia) r3
    • Major criteria
      • Need for mechanical ventilation
      • Septic shock with need for vasopressors
    • Minor criteria
      • Respiratory rate of 30 breaths per minute or more
      • Ratio of arterial partial pressure of oxygen (PaO₂) to fraction of inspired oxygen (FiO₂) of 250 or less
      • Multilobar disease
      • Leukopenia (leukocyte count less than 4000 cells/μL)
      • Uremia (BUN level of 20 mg/dL or higher)
      • Confusion or disorientation
      • Hypothermia (core temperature lower than 36 °C)
      • Thrombocytopenia (platelet count less than 100,000 cells/μL)
      • Hypotension requiring aggressive fluid resuscitation
  • Pneumonia prognostic prediction tools have also been used in practice to determine level of in-hospital care; ICU is appropriate in the following patients: r17
    • Pneumonia severity index: class V (greater than 130 points)
    • CURB-65r1 score of 4 or 5

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

Treatment Options

Determine the optimal care setting using severity of illness scores and clinical judgment r3

Begin empiric therapy based on treatment setting; in patients admitted to the hospital, give first dose before patient leaves emergency department

  • Outpatient treatment
    • First line therapy for patients without comorbidities or risk factors for antibiotic-resistant pathogens includes amoxicillin or doxycycline or a macrolide (only in areas with pneumococcal resistance to macrolides less than 25%) r3
    • For outpatient adults with the following comorbidities, antibiotic options include combination therapy or monotherapy r3
      • Comorbidities include: r3
        • Chronic heart, lung, liver, or renal disease
        • Diabetes mellitus
        • Alcohol use disorder
        • Active malignancy
        • Asplenia
      • Combination therapy r3
        • Amoxicillin-clavulanate or a cephalosporin (eg, cefpodoxime, cefuroxime), and
        • Macrolide or doxycycline
      • Monotherapy r3
        • Respiratory fluoroquinolone
    • Consider treating patients with positive test results for influenza (eg, oseltamivir), independent of duration of illness before diagnosis r3
  • General ward inpatient treatment (nonsevere community-acquired pneumonia without risk factors for MRSA, Pseudomonas aeruginosa or resistant gram-negative bacilli) r3
    • Monotherapy with an appropriate respiratory fluoroquinolone, orr3r22
    • A β-lactam plus a macrolide may be used r3r22
      • Doxycycline may be used in place of a macrolide r3
    • A systematic review showed either monotherapy with a respiratory quinolone or combination therapy with a β-lactam plus a macrolide to be superior to β-lactam monotherapy in patients requiring hospitalization r23
    • Treat patients with positive test results for influenza (eg, oseltamivir), independent of duration of illness before diagnosis; because patients with influenza often have concurrent bacterial infection, recommended antibacterial antibiotics should be administered as well, pending culture results r3
    • 2019 guidelines recommend clinicians only cover empirically for MRSA or Pseudomonas aeruginosa in adults with community-acquired pneumonia if locally validated risk factors for either pathogen are present. IDSA guidelines do not recommend empiric coverage (pending culture results) for these organisms based on individual risk factors in patients with nonsevere pneumonia r3
      • Empiric treatment options for MRSA include vancomycin or linezolid r3
      • Empiric treatment options for Pseudomonas aeruginosa include piperacillin-tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem r3
  • ICU inpatient treatment (severe community-acquired pneumonia without risk factors for MRSA or Pseudomonas aeruginosa) r3
    • β-lactam plus a macrolide r3
    • Alternatively, a β-lactam plus a respiratory fluoroquinolone may be used r3
    • Treat patients with positive test results for influenza (eg, oseltamivir), independent of duration of illness before diagnosis; because concurrent bacterial infection is common with influenza, recommended antibacterial antibiotics should be administered as well, pending culture results r3
    • 2019 American Thoracic Society and Infectious Diseases Society of America guidelines recommend clinicians only cover empirically for MRSA or Pseudomonas aeruginosa in adults with community-acquired pneumonia if locally validated risk factors for either pathogen are present. In the absence of these, clinicians may treat patients with severe pneumonia empirically for these pathogens when there is a history of recent (90 days) hospitalization and parenteral antibiotic treatment or documented past infection with these pathogens. Antibiotics should be de-escalated if indicated by culture results r3
      • Empiric treatment options for MRSA include vancomycin or linezolid r3
      • Empiric treatment options for Pseudomonas aeruginosa include: r3
        • Piperacillin-tazobactam
        • Cefepime
        • Ceftazidime
        • Aztreonam
        • Meropenem
        • Imipenem

General considerations

  • 2019 guidelines recommend that duration of antibiotic therapy should be guided by a validated measure of clinical stability. Antibiotic therapy should be continued until the patient achieves stability and for no fewer than a total of 5 days r3
    • Indicators of clinical stability: r24
      • Temperature of 37.8 °C or lower
      • Heart rate of 100 beats per minute or fewer
      • Respiratory rate of 24 breaths per minute or fewer
      • Systolic blood pressure of 90 mm Hg or higher
      • Arterial oxygen saturation of 90% or higher or PO₂ of 60 mm Hg or higher on room air
      • Ability to maintain oral intake
      • Normal mental status
  • Most patients will achieve clinical stability within the first 48 to 72 hours; thus, a total duration of therapy of 5 days should be appropriate for most patients r3
    • 2019 guidelines suggest duration of therapy for community-acquired pneumonia due to suspected or proven MRSA orPseudomonas aeruginosa should be 7 days r3
    • Other pathogens or clinical circumstances may also require a longer duration:
      • Initial therapy is not effective against identified pathogen r3
      • Staphylococcus aureus lobar pneumonia (2 weeks) r17
      • Staphylococcus aureus bacteremia (4 weeks, IV) r17
      • Mycoplasma pneumoniae or Chlamydia pneumoniae (10-14 days) r17
      • Legionella (14-21 days) r17
      • Complications caused by extrapulmonary infections (eg, meningitis, endocarditis) r3
  • If there is no improvement within 72 hours of initiation of the empiric treatment, there may be drug resistance, an unsuspected pathogen, or unrecognized complications (eg, endobronchial obstruction, empyema)
  • When culture and antibiotic susceptibility results are available, antibiotics should be adjusted to specific, narrow-spectrum therapy r3
  • Treatment can be switched from IV to oral once hemodynamic stability and clinical improvement are seen r3
  • Use of adjunctive corticosteroids remains controversial and clinical studies have produced conflicting reports. They may be considered in some cases of severe pneumonia, particularly with septic shock r3r17r22
    • 2019 Infectious Diseases Society of America guidelines recommend not routinely using corticosteroids in adults with nonsevere community-acquired pneumonia and suggest not routinely using corticosteroids in adults with severe community-acquired pneumonia or severe influenza pneumonia r3
    • 2019 Infectious Diseases Society of America guidelines endorse the Surviving Sepsis Campaign recommendationsr25 on the use of steroids in patients with septic shock refractory to adequate fluid resuscitation and vasopressor support r3

Drug therapy

  • Antibiotics r7
    • 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
        • Piperacillin Sodium, Tazobactam 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: 25 to 30 mg/kg IV loading dose for seriously ill patients, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours for at least 7 days. Adjust dose based on serum concentrations.
    • 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 r7r28c168
    • 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
Procedures
Therapeutic thoracentesis c185
General explanation
  • Drainage of pleural fluid for therapeutic (versus diagnostic) purposes:
    • Relieves dyspnea caused by a large parapneumonic effusion
    • Evacuation of purulent fluid is essential for treatment of empyema
Indication
  • Parapneumonic pleural effusion r6
    • Fluid more than 5 cm high on the lateral view of an upright chest radiograph or more than 10 mm of fluid on a lateral decubitus view
  • Pleural fluid drainage by chest tube is recommended in cases of empyema: r33
    • Pleural fluid pH is less than 7.28
    • Pleural fluid glucose level is less than 40 mg/dL
    • Ratio of pleural fluid to serum glucose is less than 0.5
    • Pleural fluid lactate dehydrogenase level is greater than 1000 units/L
Contraindications
  • No absolute contraindications
  • Relative
    • Uncorrected coagulopathy
    • Mechanically ventilated patient
    • Perform bilateral thoracentesis only after ensuring absence of pneumothorax in the first side
Complications r18
  • Pain at puncture site
  • Bleeding (eg, hematoma, hemothorax, hemoperitoneum)
  • Pneumothorax
  • Reexpansion pulmonary edema
  • Infection (eg, empyema, soft tissue infection)
  • Spleen or liver puncture
  • Vasovagal events
  • Retained intrapleural catheter fragments

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

Monitoring

  • 2019 guidelines recommend against routinely obtaining follow-up chest imaging in adults with community-acquired pneumonia whose symptoms have resolved within 5 to 7 days r3

Complications and Prognosis

Complications

  • Reduction in breathing capacity requiring mechanical ventilation c192c193
  • Empyema or lung abscess secondary to inadequately treated pleural effusion
  • Systemic complications (eg, sepsis, meningitis, bacteremia, endocarditis) c194c195c196c197
  • Pneumonia may recur in recently treated patients, particularly in high-risk groups such as elderly patients, patients who smoke, patients who have alcohol use disorder, immunosuppressed patients, or those with bronchopulmonary anatomic abnormalities c198c199c200c201c202

Prognosis

  • Outcomes are improved through early diagnosis and timely administration of antibiotics r4r34
    • Treatment within 4 to 6 hours of hospital arrival reduces mortality
  • Patients with a CURB-65r1 score of 0 to 1 or a pneumonia severity index risk class of I and II are at low risk of mortality. Mortality rate is higher in patients with higher scores or risk class
  • Infections due to Staphylococcusaureus or gram-negative bacilli and aspiration pneumonia are associated with high mortality rates for all populations
  • Incorrect diagnosis, comorbidities, inappropriate medication dose or route of administration, presence of an unusual or unanticipated pathogen, adverse drug reactions, or complications negatively impact prognosis

Screening and Prevention

Prevention

  • Tobacco use
    • Smoking cessation is important for preventing pneumonia, especially in older patients r35c203d8
  • Immunization
    • Immunocompetent persons aged 65 years and older should receive both the 23-valent pneumococcal polysaccharide vaccine and the 13-valent pneumococcal conjugate vaccine r36c204c205
      • PCV13 should be administered first, with PPSV23 administered at least 1 year later; vaccines should not be coadministered r37
      • If a dose of PPSV23 is inadvertently given earlier than the 1-year recommended interval, dose does not need to be repeated r37
      • If patient already received 1 or more doses of PPSV23, give the PCV13 dose at least 1 year after the most recent PPSV23 dose r36
    • Persons aged 19 years and older with the following comorbidities should receive both vaccines, where the 23-valent pneumococcal polysaccharide vaccine is given at least 8 weeks after 13-valent pneumococcal conjugate vaccine: r37c206c207c208c209c210c211c212c213c214c215
      • HIV infection or other congenital or acquired immunodeficiencies c216
      • Solid organ transplant c217
      • Long-term immunosuppressive therapy c218
      • Generalized malignancy c219
      • Multiple myeloma c220
      • Hodgkin disease c221
      • Leukemia or lymphoma c222
      • Nephrotic syndrome c223
      • Chronic renal failure c224
      • Cochlear implant c225
      • Functional or anatomic asplenia c226
      • Sickle cell disease and other hemoglobinopathies c227c228
      • Cerebrospinal fluid leaks c229
    • Yearly influenza vaccination is recommended for all persons 6 months of age and older r38c230
    • Dental hygiene
      • Lack of good dental hygiene is a risk factor for community-acquired pneumonia; periodic dental hygiene checks are recommended c231
Patel S: CURB-65 Severity Score. MDCalc website. Accessed September 10, 2020. http://www.mdcalc.com/curb-65-severity-score-community-acquired-pneumonia/http://www.mdcalc.com/curb-65-severity-score-community-acquired-pneumonia/Nazarian DJ et al: Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 54(5):704-31, 200919853781Metlay JP et al: Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 200(7):e45-67, 201931573350Dunbar LM et al: High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis. 37(6):752-60, 200312955634Watkins RR et al: Diagnosis and management of community-acquired pneumonia in adults. Am Fam Physician. 83(11):1299-306, 201121661712Mandell LA et al: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 44 Suppl 2:S27-72, 200717278083Metlay JP et al: Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. [online supplement]. Published 2019. Accessed September 10, 2020.https://www.atsjournals.org/doi/suppl/10.1164/rccm.201908-1581STHill AT et al: Adult outpatients with acute cough due to suspected pneumonia or influenza: CHEST guideline and expert panel report. Chest. 155(1):155-67, 201930296418Ho E: Community-acquired pneumonia in adults and children. Prim Care. 40(3):655-69, 201323958362Chalmers JD et al: Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia: systematic review and meta-analysis. Thorax. 65(10):878-83, 201020729231Levy MM et al: The Surviving Sepsis Campaign bundle: 2018 update. Crit Care Med. 46(6):997-1000, 201829767636Lim WS et al: BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 64 Suppl 3:iii1-55, 200919783532Coutinho HD et al: Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers. Int Arch Med. 1(1):24, 200818992146Long L et al: Lung ultrasound for the diagnosis of pneumonia in adults: a meta-analysis. Medicine (Baltimore). 96(3):e5713, 201728099332Llamas-Álvarez AM et al: Accuracy of lung ultrasonography in the diagnosis of pneumonia in adults: systematic review and meta-analysis. Chest. 151(2):374-82, 201727818332Orso D et al: Lung ultrasound in diagnosing pneumonia in the emergency department: a systematic review and meta-analysis. Eur J Emerg Med. 25(5):312-21, 201829189351Rider AC et al: Community-acquired pneumonia. Emerg Med Clin North Am. 36(4):665-83, 201830296998Ault MJ et al: Thoracentesis outcomes: a 12-year experience. Thorax. 70(2):127-32, 201525378543Septimus EJ: Pleural effusion and empyema. In: Bennett JE et al, eds: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Updated Edition. 8th ed. Saunders; 2015:847-54.e2https://www.clinicalkey.com//#!/content/book/3-s2.0-B978032340161600070X3-s2.0-B978032340161600070XEbell MH: Outpatient vs. inpatient treatment of community acquired pneumonia. Fam Pract Manag. 13(4):41-4, 200616671349Viasus D et al: Biomarkers for predicting short-term mortality in community-acquired pneumonia: a systematic review and meta-analysis. J Infect. 72(3):273-82, 201626777314Lee MS et al: Guideline for antibiotic use in adults with community-acquiredpneumonia. Infect Chemother. 50(2):160-98, 201829968985Lee JS et al: Antibiotic therapy for adults hospitalized with community-acquired pneumonia: a systematic review. JAMA. 315(6):593-602, 201626864413Halm EA et al: Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA. 279(18):1452-7, 19989600479Rhodes A et al: Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 43(3):304-77, 201728101605 Melinta Therapeutics, Inc: Baxdela (delafloxacin): Highlights of Prescribing Information. Melinta Therapeutics website. Revised October 2019. Accessed September 9, 2020. https://www.baxdela.com/docs/baxdela-prescribing-information.pdfhttps://www.baxdela.com/docs/baxdela-prescribing-information.pdfNabriva Therapeutics: Xenleta (lefamulin): Highlights of Prescribing Information. Nabriva Therapeutics website. Reviewed August 2019. Accessed September 10, 2020. https://www.xenleta.com/?gclid=EAIaIQobChMI-ayXzd_G5QIVCeN3Ch2igwSPEAAYASAAEgJCO_D_BwEhttps://www.xenleta.com/?gclid=EAIaIQobChMI-ayXzd_G5QIVCeN3Ch2igwSPEAAYASAAEgJCO_D_BwECDC: Influenza Antiviral Medications: Summary for Clinicians. CDC website. Updated November 15, 2019. Accessed November 22, 2019. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htmhttp://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htmGenentech USA, Inc: Xofluza (baloxavir marboxil): Highlights of Prescribing Information. Genentech website. Revised October 2019. Accessed September 10, 2020. https://www.xofluza.com/hcp/why-xofluza/mechanism-of-action.htmlhttps://www.xofluza.com/hcp/why-xofluza/mechanism-of-action.htmlZhang Y et al: Oxygen therapy for pneumonia in adults. Cochrane Database Syst Rev. 3:CD006607, 201222419316Agency for Healthcare Research and Quality: Treating Tobacco Use and Dependence: 2008 Update. AHRQ website. Published 2008. Reviewed April 2013. Accessed September 10, 2020. https://www.ahrq.gov/prevention/guidelines/tobacco/clinicians/update/index.html#https://www.ahrq.gov/prevention/guidelines/tobacco/clinicians/update/index.html#Rigotti NA et al: Interventions for smoking cessation in hospitalised patients. Cochrane Database Syst Rev. 5:CD001837, 201222592676Sahn SA: Diagnosis and management of parapneumonic effusions and empyema. Clin Infect Dis. 45(11):1480-6, 200717990232Meehan TP et al: Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA. 278(23):2080-4, 19979403422Nuorti JP et al: Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med. 342(10):681-9, 200010706897CDC: Pneumococcal Vaccine Recommendations. CDC website. Last reviewed November 21, 2019. Accessed September 10, 2020. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/recommendations.htmlhttps://www.cdc.gov/vaccines/vpd/pneumo/hcp/recommendations.htmlKobayashi M et al: Intervals between PCV13 and PPSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 64(34):944-7, 201526334788Grohskopf LA et al: Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices — United States, 2020–21 influenza season. MMWR Recomm Rep. 69(8):1-24, 2020https://www.cdc.gov/mmwr/volumes/69/rr/rr6908a1.htm
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