Residency · Residency · Infectiousdisease

Community-Acquired Pneumonia

Epidemiology and Burden

Scope of Disease

Community-acquired pneumonia is responsible for approximately 1.5 million adult hospitalizations annually in the United States and remains the leading infectious cause of death. Thirty-day mortality varies dramatically by care setting: outpatient mortality is 1 to 5 percent, inpatient mortality rises to 5 to 15 percent, and among patients requiring ICU admission, mortality reaches 20 to 50 percent. The annual cost of CAP exceeds 10 billion dollars in the United States. The ATS/IDSA 2019 guidelines represent the current standard of care and introduced several important paradigm shifts in empiric therapy and risk stratification.

Microbiology

Streptococcus pneumoniae remains the most commonly identified bacterial pathogen in CAP, though it is essential to appreciate that no pathogen is identified in 50 to 60 percent of cases despite comprehensive testing. Atypical organisms, including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila, represent important causes requiring coverage in empiric regimens. Viral etiologies, including influenza, SARS-CoV-2, RSV, parainfluenza, rhinovirus, and human metapneumovirus, are increasingly recognized as the sole cause in 25 to 30 percent of cases, as demonstrated by the landmark EPIC study by Jain and colleagues in 2015. S. aureus pneumonia is particularly associated with post-influenza secondary infection and necrotizing pneumonia. Gram-negative organisms, including Klebsiella in the setting of alcoholism and diabetes, and Pseudomonas in patients with structural lung disease or recent hospitalization, are important considerations in specific clinical contexts. Anaerobic organisms contribute when aspiration is the mechanism. The EPIC study's finding that rhinovirus and influenza were the most commonly detected organisms when comprehensive testing was performed fundamentally challenged traditional assumptions about CAP microbiology.

Severity Assessment and Site-of-Care Decision

CURB-65 Score

The CURB-65 score incorporates five variables: Confusion, Urea above 7 millimoles per liter (BUN above 20), Respiratory rate of 30 or above, Blood pressure with systolic below 90 or diastolic of 60 or below, and Age 65 or above. A score of 0 to 1 supports outpatient management, a score of 2 suggests a short inpatient stay or close outpatient follow-up, and scores of 3 to 5 indicate inpatient management with scores of 4 to 5 warranting consideration of ICU admission.

PSI/PORT Score

The Pneumonia Severity Index, developed from the Pneumonia Patient Outcomes Research Team, incorporates 20 variables including age, comorbidities, laboratory values, and vital signs to classify patients into five risk classes. Classes I and II are appropriate for outpatient therapy, class III may warrant short observation, and classes IV and V require inpatient management. The PSI is better validated than CURB-65 for identifying low-risk patients suitable for outpatient therapy.

ATS/IDSA Criteria for Severe CAP (ICU Admission)

The ATS/IDSA criteria for severe CAP define major criteria, of which one is required, as septic shock necessitating vasopressors or respiratory failure requiring mechanical ventilation. Minor criteria, of which three or more of nine are required, include respiratory rate of 30 or above, PaO2/FiO2 ratio of 250 or below, multilobar infiltrates, confusion, BUN of 20 or above, white blood cell count below 4,000, platelets below 100,000, temperature below 36 degrees Celsius, and hypotension requiring aggressive fluid resuscitation. The presence of severe CAP mandates ICU-level care and broader empiric antibiotic coverage.

<image>A clinical decision-making flowchart for CAP site-of-care determination. Start with "CAP diagnosis confirmed (clinical + radiographic)." First step: "Calculate severity score (CURB-65 or PSI)." Branch into three pathways: "Low severity (CURB-65 0-1, PSI I-II)" leading to "Outpatient treatment," "Moderate severity (CURB-65 2, PSI III)" leading to "Consider short observation or supervised outpatient," and "High severity (CURB-65 3-5, PSI IV-V)" leading to "Inpatient admission." For inpatients, add a second assessment: "ATS/IDSA severe CAP criteria?" with "Yes (≥1 major or ≥3 minor)" leading to "ICU admission + expanded empiric coverage" and "No" leading to "General ward." Include the specific antibiotic regimens for each level of care in boxes at the bottom. Use a professional clinical algorithm format with green (outpatient), yellow (ward), and red (ICU) color coding.</image>

Diagnostic Workup

Recommended Testing

All hospitalized patients should receive blood cultures from two sites, sputum Gram stain and culture when a quality specimen is obtainable, a respiratory viral panel by PCR, Legionella urinary antigen, and pneumococcal urinary antigen. For severe CAP, all of the above testing should be obtained, with consideration of bronchoscopy with bronchoalveolar lavage in intubated patients. Procalcitonin may assist in distinguishing bacterial from viral pneumonia, with levels below 0.25 micrograms per liter arguing against typical bacterial CAP, and serial measurements guide treatment duration decisions. Sputum quality is assessed by the presence of more than 25 polymorphonuclear cells and fewer than 10 squamous epithelial cells per low-power field.

When to Consider MRSA/Pseudomonas Risk Factors

The 2019 ATS/IDSA guidelines represent a deliberate departure from the prior practice of reflexively broadening empiric therapy. Empiric MRSA or anti-pseudomonal coverage should be added only when locally validated risk factors are present. MRSA risk factors include a prior MRSA respiratory culture, recent hospitalization with intravenous antibiotics, and cavitary or necrotizing pneumonia. Pseudomonas risk factors include a prior Pseudomonas respiratory culture, structural lung disease such as bronchiectasis or cystic fibrosis, and recent hospitalization with intravenous antibiotics. The key teaching point is that vancomycin and piperacillin-tazobactam should not be reflexively added for all hospitalized CAP. When empiric MRSA or Pseudomonas coverage is initiated, de-escalation should occur within 48 hours if cultures are negative.

Antibiotic Therapy

Outpatient Treatment (No Comorbidities)

Outpatient therapy for healthy patients without comorbidities consists of amoxicillin 1 gram orally three times daily as high-dose pneumococcal coverage, or doxycycline 100 milligrams orally twice daily, or azithromycin 500 milligrams on day 1 followed by 250 milligrams daily for 4 days, with the caveat that azithromycin should only be used if local pneumococcal macrolide resistance is below 25 percent.

Outpatient Treatment (With Comorbidities)

For patients with comorbidities including chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancy, asplenia, immunosuppression, or prior antibiotic use within three months, outpatient therapy consists of amoxicillin-clavulanate 875/125 milligrams orally twice daily plus azithromycin or doxycycline, or respiratory fluoroquinolone monotherapy with levofloxacin 750 milligrams daily or moxifloxacin 400 milligrams daily. Fluoroquinolones should be used with caution given FDA black box warnings regarding tendon rupture, peripheral neuropathy, aortic aneurysm, and CNS effects, and should be reserved for patients who cannot tolerate alternatives.

Inpatient, Non-Severe

Non-severe inpatient CAP is treated with a beta-lactam such as ceftriaxone 1 to 2 grams intravenously daily or ampicillin-sulbactam 3 grams intravenously every 6 hours plus azithromycin 500 milligrams intravenously or orally daily, or with respiratory fluoroquinolone monotherapy. Combination therapy with a beta-lactam plus macrolide is preferred over fluoroquinolone monotherapy in most situations.

Inpatient, Severe CAP (ICU)

Severe CAP requires a beta-lactam such as ceftriaxone 2 grams intravenously daily or ampicillin-sulbactam plus azithromycin 500 milligrams intravenously daily, or a beta-lactam plus a respiratory fluoroquinolone. If MRSA risk factors are present, vancomycin or linezolid is added. If Pseudomonas risk factors exist, an anti-pseudomonal beta-lactam such as piperacillin-tazobactam, cefepime, or meropenem is substituted for ceftriaxone.

Special Situations

Aspiration pneumonia is treated with amoxicillin-clavulanate or ampicillin-sulbactam, with the important distinction that routine anaerobic coverage is not recommended for aspiration pneumonitis as opposed to documented aspiration pneumonia. Legionella pneumonia is treated with a fluoroquinolone or azithromycin for 5 to 14 days. Influenza with secondary bacterial pneumonia requires oseltamivir plus ceftriaxone plus vancomycin, reflecting the high rate of staphylococcal superinfection in this clinical setting.

Duration of Therapy

Short-Course Evidence

The 2019 ATS/IDSA guidelines recommend a minimum of 5 days of therapy, with discontinuation permitted when the patient has been clinically stable for at least 48 hours, including defervescence, improving vital signs, tolerance of oral intake, and normal mentation. Longer courses are reserved for complications such as empyema, lung abscess, or extrapulmonary infection. Procalcitonin-guided antibiotic discontinuation, with a stopping criterion of PCT below 0.25 or greater than 80 percent decline from peak, reduces antibiotic duration by 2 to 3 days without adverse outcomes. There is no benefit to extending therapy beyond clinical stability, and longer courses increase adverse effects and resistance.

Adjunctive Therapies

Corticosteroids in Severe CAP

The CAPE COD trial published in 2023 provided the strongest evidence to date for corticosteroids in severe CAP, demonstrating that hydrocortisone 200 milligrams intravenously daily for 4 to 8 days reduced 28-day mortality from 11.9 percent to 6.2 percent, yielding a number needed to treat of approximately 18. Prior studies had yielded mixed results, though the Stern 2017 meta-analysis and the Meduri 2022 study both suggested benefit in severe cases. Current practice favors considering corticosteroids for severe CAP requiring ICU admission or high-flow oxygen, while avoiding corticosteroids in influenza and fungal pneumonia. The recommended dose is hydrocortisone 200 milligrams per day or methylprednisolone equivalent, tapered over 5 to 8 days.

<image>An evidence summary infographic for the CAPE COD trial on corticosteroids in severe CAP. Show the trial design at the top: "Multicenter, double-blind, RCT, N=800, severe CAP requiring ICU or high-flow oxygen." Main results in large text: "28-day mortality: 6.2% (hydrocortisone) vs. 11.9% (placebo), p=0.006, NNT=18." Include a Kaplan-Meier survival curve showing separation of the two groups. Below, show secondary outcomes: "Vasopressor-free days, ventilator-free days - both favored hydrocortisone." Safety outcomes: "Insulin use increased, no difference in GI bleeding or secondary infections." Include a "Clinical Implication" box: "Consider hydrocortisone 200mg IV daily x 4-8 days for severe CAP (excluding influenza/fungal)." Use blue for the treatment group and gray for placebo in all graphs.</image>

Prevention

Vaccination

PCV20 (Prevnar 20) is recommended for all adults aged 65 and above and for adults aged 19 to 64 with risk conditions, replacing the previous sequential PCV13 plus PPSV23 approach. Annual influenza vaccination reduces influenza-associated pneumonia hospitalizations. COVID-19 vaccination reduces severe pneumonia from SARS-CoV-2. Smoking cessation remains the single most impactful modifiable risk factor for CAP prevention.

Key Clinical Pearls

• The EPIC study showed that no pathogen is identified in >50% of CAP cases -- empiric therapy must cover typical and atypical organisms
• Do not reflexively add MRSA or Pseudomonas coverage for hospitalized CAP -- the 2019 ATS/IDSA guidelines specifically advise against this unless validated risk factors are present
• 5 days of therapy is sufficient for uncomplicated CAP when the patient meets clinical stability criteria at 48 hours
• The CAPE COD trial provides the strongest evidence for corticosteroids in severe CAP -- hydrocortisone 200mg/day reduces mortality with NNT of 18
• PCT-guided antibiotic discontinuation is a validated strategy to shorten CAP treatment duration
• Respiratory fluoroquinolones are powerful drugs but carry significant adverse effects -- reserve for patients who cannot tolerate beta-lactam/macrolide combinations
• Always obtain Legionella and pneumococcal urinary antigens for hospitalized CAP -- positive results guide de-escalation

References

1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official ATS/IDSA clinical practice guideline. Am J Respir Crit Care Med. 2019;200(7):e45-e67.
2. Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults (EPIC study). N Engl J Med. 2015;373(5):415-427.
3. Dequin PF, Meziani F, Quenot JP, et al. Hydrocortisone in severe community-acquired pneumonia (CAPE COD). N Engl J Med. 2023;388(21):1931-1941.
4. Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10:CD007498.
5. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia (PSI/PORT). N Engl J Med. 1997;336(4):243-250.

Read this lecture as Markdown