Pneumonia

Pneumonia is a common infection and a major cause of death, particularly in the elderly. Key management points include prompt recognition of the underlying microbe, which can be diverse, and prescribing the right antibiotics for bacterial infection, which can be challenging in an era of increasing antimicrobial resistance and concurrent need for better stewardship. For information on Covid-19, please see the NEJM Coronavirus (Covid-19) Topic Page.

In this section, we cover:

• Community-Acquired Pneumonia

• Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia

• Aspiration Pneumonia

Community-Acquired Pneumonia

A distinguishing feature of community-acquired pneumonia (CAP) is that it is caused by organisms that are less likely to have developed drug resistance. CAP is more likely to develop in patients who have not been hospitalized within the past 90 days or are not regularly exposed to the health care system. In a contemporary cohort of hospitalized patients, no specific pathogen was detected in approximately 60% of cases, and coinfection with virus and bacteria was common.

(Source: Community-Acquired Pneumonia. N Engl J Med 2014.)

Common pathogens include:

• viruses: human rhinovirus, influenza A/B, human metapneumovirus, parainfluenza virus, respiratory syncytial virus

• Streptococcus pneumoniae: the most common bacteria, with decreasing incidence due to vaccination and smoking cessation

• Haemophilus influenzae and Moraxella catarrhalis: more likely in patients with chronic obstructive pulmonary disease (COPD)

• Mycoplasma pneumoniae and Chlamydophila pneumoniae: “atypical” bacteria

• Staphylococcus aureus: increased risk with concurrent influenza infection or glucocorticoid use, increasing community-acquired methicillin-resistant Staphylococcus aureus (MRSA) incidence with characteristic features

• Legionella pneumophilia: uncommon but can have severe presentation

• Pseudomonas aeruginosa and other gram-negative bacilli: normally rare, but more common with structural lung disease (e.g., COPD, bronchiectasis)

(Source: Community-Acquired Pneumonia. N Engl J Med 2014.)

Diagnosis and Testing

Diagnosis of pneumonia is clinical and classically based on the following triad:

• signs of infection (e.g., fever, chills, leukocytosis)

• respiratory symptoms (e.g., cough, sputum production, shortness of breath, pleuritic chest pain)

• new lung infiltrate on imaging

However, the diagnosis can be challenging with a broad differential diagnosis. Symptoms may be absent or mild in elderly or immunocompromised patients. Existing lung disease or technical difficulties may obscure radiographic findings.

(Source: Community-Acquired Pneumonia. Engl J Med 2014.)

Laboratory testing: In addition to basic labs, consider the tests listed below. Outpatients are typically treated empirically due to costs associated with testing. More-severe presentations warrant more testing.

• sputum culture and Gram stain: helpful with good specimen (i.e., >10 inflammatory cells per epithelial cell); decreasing yield within 6 hours of antibiotic administration

• blood cultures: in severe cases or those predisposed to bacteremia (e.g., asplenia)

• Legionella and pneumococcal urine antigen tests: should only be performed in patients with severe CAP, unless local outbreaks or recent travel support use of the Legionella antigen test

• polymerase chain reaction (PCR) for influenza: during flu season

• testing for SARS CoV-2 infection

• polymerase chain reaction (PCR) for M. pneumoniae, C. pneumoniae, and respiratory viruses: helpful for identifying a cause and for antimicrobial stewardship if paired with early termination of antibiotics

• arterial blood gas and lactate: helpful for diagnosing sepsis, acute respiratory distress syndrome (ARDS), or both

• procalcitonin: some data suggest that procalcitonin can be used to guide antibiotic treatment based on threshold (≥0.25 μg/liter is more likely bacterial and ≤0.1 μg/liter is more likely viral or atypical) or trend; some evidence (although conflicting) suggests that its use is associated with lower antibiotic use and mortality risk

Risk stratification: The following are validated tools for determining the best treatment setting (outpatient, inpatient, or intensive care unit [ICU]):

• CURB-65 is simple and easy to use. A score ≥2 predicts high 30-day mortality and inpatient admission is recommended; admission to an intensive care setting should be considered for patients with scores ≥3.

  • confusion

  • Blood urea nitrogen (BUN) >7 mmol/liter or 19 mg/dL

  • respiratory rate ≥30

  • systolic blood pressure <90 mm Hg or diastolic blood pressure ≤60 mm Hg

  • Age ≥65

• Pneumonia Severity Index (PSI) is more sensitive than CURB-65 but more complicated to use. PSI is useful when patients have less than two CURB-65 criteria but still have comorbidities that could predict failure of outpatient therapy.

• SMART-COP is designed to predict the need for ICU care based on the following criteria:

  • systolic blood pressure

  • multilobar chest x-ray involvement

  • albumin

  • respiratory rate

  • tachycardia

  • confusion

  • oxygen level

  • Arterial pH

• The 2019 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines recommend ICU admission in patients with ≥3 of the following criteria:

  • confusion

  • BUN ≥20 mg/dL

  • respiratory rate ≥30

  • multilobar infiltrates

  • PaO₂/FiO₂ ratio <250

  • platelet count <100,000 cells/mm³

  • systolic pressure <90 mm Hg

  • temperature <36°C

  • leukocyte count <4000/mm³

Treatment

Outpatient: Beta-lactams are used to treat most common bacteria. However, beta-lactamase production is increasing, and a beta-lactamase inhibitor may be helpful. Macrolides, fluoroquinolones, and tetracyclines are used to treat atypical organisms and Legionella, as well as common bacterial causes.

The ATS/IDSA guidelines recommend empiric treatment as follows:

• azithromycin: preferred if community S. pneumoniae macrolide resistance is <25%

• doxycycline: alternative if azithromycin cannot be used

• for patients at risk of drug resistance (e.g., chronic heart, lung, liver, or renal disease; diabetes; alcoholism; cancer; asplenia; immunosuppression; use of antibiotics in the past 3 months):

  • respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin)

  • beta-lactam (e.g., high-dose amoxicillin, amoxicillin-clavulanate, cefpodoxime, cefuroxime) and azithromycin

Inpatient: Start with parenteral antibiotics and switch to an oral regimen once the patient is stable and improving clinically. Patients do not need to be observed on oral therapy before discharge. ATS/IDSA guidelines recommend either:

• beta-lactam (e.g., ceftriaxone, ampicillin-sulbactam) and azithromycin

• respiratory fluoroquinolones: excellent bioavailability

ICU: Patients in the ICU require a minimum of the recommended inpatient treatment described above. Concurrent sepsis and ARDS should be managed as appropriate (see Sepsis and ARDS in the Critical Care rotation guide).

Additional treatments:

• oseltamivir: add during influenza season even if >48 hours have elapsed after symptom onset; can be stopped if PCR is negative

• vancomycin, linezolid, or ceftaroline: for patients at risk for MRSA

• piperacillin-tazobactam, cefepime, or carbapenems: for patients at risk for P. aeruginosa (e.g., those with COPD, bronchiectasis, or undergoing treatment with glucocorticoids or other immunosuppressive drugs)

(Source: Community-Acquired Pneumonia. N Engl J Med 2023.)

Treatment duration: Treatment is generally prescribed for 5 to 7 days in patients with prompt response to therapy but can vary based on organism and severity. For example, S. aureus frequently causes abscesses, cavitation, or both and requires treatment for 2 to 4 weeks. Legionella is treated for 2 weeks.

Glucocorticoids: Pneumonia can lead to ARDS and sepsis, due to local and systemic inflammation that can be reduced by glucocorticoids. For severe pneumonia and refractory septic shock, glucocorticoids may decrease length of hospitalization and need for mechanical ventilation. Glucocorticoids should be used with caution, weighing risks (e.g., hyperglycemia, gastrointestinal bleed, delirium) against benefits.

Other treatment considerations:

• Alternative causes: Consider other causes when a patient does not improve as expected on appropriate therapy (see table below of reasons for a lack of response to treatment).

• Prevention: Every patient who qualities for pneumococcal vaccination should receive it.

• Follow-up chest radiograph: Follow-up chest imaging is not recommended according to the 2019 ATS/IDSA guidelines. Some patients with CAP may be eligible for lung-cancer screening based on their initial workup, and this should be performed as clinically indicated.

(Source: Community-Acquired Pneumonia. N Engl J Med 2014.)

Pao2 denotes partial pressure of arterial oxygen, and Fio2 the fraction of inspired oxygen. (Source: Community-Acquired Pneumonia. N Engl J Med 2023.)

Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia

Distinguishing hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) from CAP is important because the causative organisms tend to be different and more resistant to antibiotics. HAP and VAP are associated with greater mortality. The primary microbes of concern are S. aureus and P. aeruginosa.

Definitions:

• HAP: pneumonia occurring ≥48 hours after hospitalization, not present on admission, and not associated with mechanical ventilation

• VAP: pneumonia occurring ≥48 hours after endotracheal intubation

Diagnosis

Diagnosis of VAP is especially challenging because patients are often unable to report symptoms and the diagnosis is suggested by increased ventilation requirement or routine laboratory and imaging studies. An endotracheal aspiration sample is sufficient to diagnose VAP, and an invasive sample from bronchoalveolar lavage may be sufficient to rule out in the right setting. The ultimate diagnosis relies on overall clinical assessment rather than any specific test.

Treatment

Use your local antibiogram and obtain microbiologic samples whenever possible. The aggressiveness of empiric treatment should be determined by a patient’s mortality risk and local resistance patterns. A 7-day course is recommended, but ultimate length depends on clinical improvement.

Risk factors for drug-resistance include:

• intravenous (IV) antibiotic use within 90 days

• septic shock at the time of VAP

• ARDS

• ≥5 days of hospitalization

• acute renal replacement therapy preceding onset of VAP

Empiric treatment: Typical regimens will target S. aureus, P. aeruginosa, and other gram-negative bacilli.

• MRSA: vancomycin, linezolid, ceftaroline (note: daptomycin, while active against MRSA, binds strongly to lung surfactant and cannot treat pneumonia)

• methicillin-susceptible Staphylococcus aureus (MSSA): nafcillin, cefazolin

• P. aeruginosa

  • Beta-lactam: piperacillin-tazobactam, cephalosporins (e.g., cefepime, ceftazidime), carbapenems (e.g., imipenem, meropenem), aztreonam

  • Non-beta-lactam: fluoroquinolones (e.g., ciprofloxacin, levofloxacin), aminoglycosides (e.g., amikacin, gentamicin, tobramycin)

  • Monotherapy can be considered for low-risk patients in settings with low resistance rates. Otherwise, patients should receive one agent each from beta-lactam and non-beta-lactam categories.

• structural lung disease (e.g., bronchiectasis, cystic fibrosis): two antipseudomonal agents

Aspiration Pneumonia

Aspiration commonly causes pneumonia in nursing home residents. However, not every aspiration event leads to infection, and aspiration pneumonitis, a chemical injury to the lungs, can present similarly to pneumonia, with fever, leukocytosis, respiratory symptoms, and infiltrate. While gastric content is typically sterile due to low pH, certain conditions predispose to colonization, such as antacid therapy, foreign object (e.g., feeding tube), or poor motility (e.g., gastroparesis, small-bowel obstruction, ileus).

If aspiration was unwitnessed, other features may suggest aspiration pneumonia over CAP, such as radiographic location (posterior segments of the upper lobes and apical segments of the lower lobes when recumbent during aspiration and basal segments of the lower lobes when upright), predisposition for swallowing difficulty (e.g., stroke, recent sedation), or risk factors for colonization as noted above.

Treatment

Distinguish pneumonia from pneumonitis. Timing is crucial; pneumonitis may occur within hours whereas pneumonia may take days. For stable patients, it may be helpful to monitor for 48 hours and start antibiotics if symptoms persist. Alternatively, discontinue antibiotics if symptoms resolve quickly (within 48-72 hours). Antibiotic regimens can target aerobes and anaerobes.

• oral: amoxicillin-clavulanate, clindamycin

• parenteral: ampicillin-sulbactam, ceftriaxone, piperacillin-tazobactam, carbapenems

(Source: Aspiration Pneumonitis and Aspiration Pneumonia. N Engl J Med 2001.)