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General Considerations
Community-acquired pneumonia (CAP) is a common disorder, with approximately 4-5 million cases diagnosed each year in the United States, at least 25% of which require hospitalization. It is the deadliest infectious disease in the United States and is routinely among the top 10 causes of death. Mortality in milder cases treated as outpatients is less than 1%. Among patients hospitalized for CAP, in-hospital mortality is approximately 10-12% and 1-year mortality (in those over age 65) is greater than 40%. Risk factors for the development of CAP include older age; tobacco use; excessive alcohol use; comorbid medical conditions, especially COPD or other chronic lung disease; immunosuppression; and recent viral upper respiratory tract infection.
The patient's history, physical examination, and imaging studies are essential to establishing a diagnosis of CAP. None of these efforts identifies a specific microbiologic cause, however. Sputum examination may be helpful in selected patients but 40% of patients cannot produce an evaluable sputum sample; additionally, test characteristics of sputum Gram stain and culture vary by organism and lack sensitivity for some of the most common causes of pneumonia. Since patient outcomes improve when the initial antibiotic choice is appropriate for the infecting organism, the American Thoracic Society and the Infectious Diseases Society of America recommend empiric treatment based on epidemiologic data (Table 9-10. Recommended Empiric Antibiotics for Community-Acquired Bacterial Pneumonia). Such treatment improves initial antibiotic coverage, reduces unnecessary hospitalization, and improves 30-day survival.
Definition & Pathogenesis
CAP is diagnosed outside of the hospital setting or within the first 48 hours of hospital admission. Pulmonary defense mechanisms (cough reflex, mucociliary clearance system, immune responses) normally prevent the development of lower respiratory tract infections following aspiration of oropharyngeal secretions containing bacteria or inhalation of infected aerosols. CAP occurs when there is a defect in one or more of these normal defense mechanisms or when a large infectious inoculum or a virulent pathogen overwhelms the immune response.
Prospective studies fail to identify the cause of CAP in 30-60% of cases; two or more causes are identified in up to one-third of cases. The most common bacterial pathogen identified in most studies of CAP is S pneumoniae, accounting for approximately two-thirds of bacterial isolates. Other common bacterial pathogens include H influenzae, M pneumoniae, C pneumoniae, S aureus, Moraxella catarrhalis, Klebsiella pneumoniae, other gram-negative rods, and Legionella species. Common viral causes of CAP include coronaviruses (SARS-CoV-2, MERS), influenza virus, respiratory syncytial virus, adenovirus, and parainfluenza virus. A detailed assessment of epidemiologic risk factors may aid in diagnosing pneumonias due to the following uncommon causes: Chlamydophila psittaci (psittacosis); Coxiella burnetii (Q fever); Francisella tularensis (tularemia); Blastomyces, Coccidioides, Histoplasma (endemic fungi); and Sin Nombre virus (hantavirus pulmonary syndrome).
Clinical Findings
A. Symptoms and Signs
Most patients with CAP experience an acute or subacute onset of fever, cough with or without sputum production, and dyspnea. Other common symptoms include sweats, chills, rigors, chest discomfort, pleurisy, hemoptysis, fatigue, myalgias, anorexia, headache, and abdominal pain. Persons over age 80, however, may have an atypical presentation, including falls, delirium, lethargy, and anorexia.
Common physical findings include fever or hypothermia, tachypnea, tachycardia, and arterial oxygen desaturation. Many patients appear acutely ill. Chest examination often reveals inspiratory crackles, rhonchi, and bronchial breath sounds. Dullness to percussion may be observed if lobar consolidation or a parapneumonic pleural effusion is present. The clinical evaluation is less than 50% sensitive compared to chest imaging for the diagnosis of CAP (see Imaging Pulmonary Disorders section below). In most patients, therefore, a CXR is essential to the evaluation of suspected CAP.
B. Diagnostic Testing
Diagnostic testing for a specific infectious cause of CAP is not generally indicated in outpatients because empiric antibiotic therapy is almost always effective in this population. In ambulatory outpatients whose presentation (travel history, exposure) suggests an etiology not covered by standard therapy (eg, Coccidioides) or public health concerns (eg, SARS-CoV-2, Mycobacterium tuberculosis, influenza), diagnostic testing is appropriate. Diagnostic testing is recommended in hospitalized CAP patients for multiple reasons: the likelihood of an infectious cause unresponsive to standard therapy is higher in more severe illness, the inpatient setting allows narrowing of antibiotic coverage as specific diagnostic information is available, and the yield of testing is improved in more acutely ill patients.
Diagnostic tests are used to adjust empirically chosen therapy and to facilitate epidemiologic analysis. Three widely available diagnostic tests may guide therapy: the sputum Gram stain and culture, urinary antigen tests for S pneumoniae and Legionella species, and tests for viruses such as influenza and SARS-CoV-2 (see COVID-19 discussion, Chapter 34). The usefulness of a sputum Gram stain lies in broadening initial coverage in patients to be hospitalized for CAP, most commonly to cover S aureus (including community-acquired methicillin-resistant S aureus [CA-MRSA] strains) or gram-negative rods (including P aeruginosa and Enterobacteriaceae). Urinary antigen assays for Legionella pneumophila and S pneumoniae are at least as sensitive and specific as sputum Gram stain and culture. Results of antigen testing are not affected by initiation of antibiotic therapy, and positive tests may allow narrowing of initial antibiotic coverage. Urinary antigen assay for S pneumoniae should be ordered for patients with leukopenia or asplenia or those with severe disease. Urinary antigen assay for L pneumophila should be ordered for patients in an area with an outbreak, with recent travel, with severe disease, or in whom a high clinical index of suspicion exists. Rapid influenza and SARS-CoV-2 testing has intermediate sensitivity but high specificity, with sensitivity depending on the method of detection (nucleic acid or PCR-based tests have higher sensitivity than antigen-based detection). Positive tests for viruses may direct isolation of hospitalized patients but do not necessarily reduce the need for antibacterial therapy, since coinfection with a bacterial pathogen occurs.
Rapid turnaround multiplex-PCR amplification from lower respiratory tract samples is increasingly available. Different commercial products can identify multiple strains of bacteria and viruses, in addition to genes that encode for antibiotic resistance. Early experience with multiplex-PCR shows improved overall diagnostic yield, particularly for viral infections, and a higher incidence of bacterial/viral coinfection than previously recognized. Limitations of multiplex-PCR include cost and availability, in addition to the challenge of interpreting potentially false-positive results from a highly sensitive test, since either viral or bacterial pathogens may colonize the airways. Some guidelines recommend against testing for viruses other than influenza or SARS-CoV-2 in outpatients or immunocompetent inpatients, as results of ancillary viral tests have not been found to impact management or outcomes in these categories of patients.
Additional microbiologic testing including pre-antibiotic sputum and blood cultures (at least two sets at separate sites) has been standard practice for patients with CAP who require hospitalization. The yield of blood and sputum cultures is low, however; false-positive results are common, and the impact of culture results on patient outcomes is small. As a result, targeted testing is recommended for patients with severe disease and for those treated empirically for MRSA or P aeruginosa infection. The role of culture is to allow narrowing of initial empiric antibiotic coverage, adjustment of coverage based on specific antibiotic resistance patterns, to identify unsuspected pathogens not covered by initial therapy, and to provide information for epidemiologic analysis.
Apart from microbiologic testing, hospitalized patients should undergo CBC with differential and a chemistry panel (including serum glucose, electrolytes, BUN, creatinine, bilirubin, and liver enzymes). Hypoxemic patients should have ABGs sampled. Test results help assess severity of illness and guide evaluation and management. HIV testing should be considered in all adult patients and performed in those with risk factors.
C. Imaging
A pulmonary opacity on CXR or CT scan is required to establish a diagnosis of CAP. Chest CT scan is more sensitive and specific than chest radiography and may be indicated in selected cases. Radiographic findings range from patchy airspace opacities to lobar consolidation with air bronchograms to diffuse alveolar or interstitial opacities. Additional findings can include pleural effusions and cavitation. Chest imaging cannot identify a specific microbiologic cause of CAP; no pattern of radiographic abnormalities is pathognomonic of any infectious cause.
Chest imaging may help assess severity and response to therapy over time. Progression of pulmonary opacities during antibiotic therapy or lack of radiographic improvement over time are poor prognostic signs and raise concerns about secondary or alternative pulmonary processes. Clearing of pulmonary opacities in patients with CAP can take 6 weeks or longer. Clearance is usually quickest in younger patients, nonsmokers, and those with only single-lobe involvement. Routine follow-up chest imaging is not indicated for most patients with CAP.
D. Special Examinations
Patients with CAP who have significant pleural fluid collections may require diagnostic thoracentesis (with pleural fluid sent for glucose, LD, and total protein levels; leukocyte count with differential; pH determination; and Gram stain and culture). Positive pleural cultures indicate the need for tube thoracostomy drainage.
Patients with cavitary opacities should have sputum fungal and mycobacterial cultures.
Sputum induction or fiberoptic bronchoscopy to obtain samples of lower respiratory secretions are indicated in patients with a worsening clinical course who cannot provide expectorated sputum samples or who may have pneumonia caused by M tuberculosis infection or certain opportunistic infections, including Pneumocystis jirovecii.
Procalcitonin is a biomarker that is typically associated with bacterial rather than viral infection; however, studies have not found a threshold at which bacterial pneumonia can be reliably distinguished from viral pneumonia. Therefore, procalcitonin is not recommended as a “rule-out” test for bacterial pneumonia, and empiric antibacterial agents are recommended regardless of procalcitonin level at time of presentation. The kinetics of decline in procalcitonin level may be used to discontinue antibiotic therapy after a threshold duration of antibiotics (at least 5 days) has been met; such use decreases antibiotic exposure, with possible improvement in mortality.
Differential Diagnosis
The differential diagnosis of lower respiratory tract infection is extensive and includes upper respiratory tract infections, reactive airway diseases, HF, interstitial pneumonias, lung cancer, pulmonary vasculitis, pulmonary thromboembolic disease, and atelectasis.
Treatment
Two general principles guide antibiotic therapy once the diagnosis of CAP is established: prompt initiation of a medication to which the etiologic pathogen is susceptible.
In patients who require specific diagnostic evaluation, sputum and blood culture specimens should be obtained prior to initiation of antibiotics. Since early administration of antibiotics to acutely ill patients is associated with improved outcomes, obtaining other diagnostic specimens or test results should not delay the initial dose of antibiotics.
Optimal antibiotic therapy would be pathogen directed, but a definitive microbiologic diagnosis is not typically available on presentation. A syndromic approach to therapy, based on clinical presentation and chest imaging, does not reliably predict the microbiology of CAP. Therefore, initial antibiotic choices are empiric, based on acuity (treatment as an outpatient, inpatient, or in the ICU), patient risk factors for specific pathogens, and local antibiotic resistance patterns (Table 9-10. Recommended Empiric Antibiotics for Community-Acquired Bacterial Pneumonia).
Since S pneumoniae remains a common cause of CAP in all patient groups, local prevalence of drug-resistant S pneumoniae significantly affects initial antibiotic choice. Prior treatment with one antibiotic in a pharmacologic class (eg, beta-lactam, macrolide, fluoroquinolone) predisposes to the emergence of drug-resistant S pneumoniae, with resistance developing against that class of antibiotics to which the pathogen was previously exposed. Current in vivo efficacy appears to justify maintaining macrolides as first-line therapy except in areas where there is a high prevalence of resistant strains. Macrolide resistance has increased (approximately one-third of S pneumoniae isolates now show in vitro resistance); however, reported treatment failures remain rare compared to the number of patients treated. S pneumoniae resistance to fluoroquinolones is rare in the United States but is increasing.
CA-MRSA is genetically and phenotypically different from hospital-acquired MRSA strains and is more virulent. CA-MRSA is a rare cause of necrotizing pneumonia, empyema, respiratory failure, and shock; it appears to be associated with prior influenza infection. Linezolid may be preferred to vancomycin in treatment of CA-MRSA pulmonary infection due to bacterial toxin inhibition, but data have not demonstrated clear benefit over vancomycin. Daptomycin should not be used in any MRSA pneumonia because it does not achieve adequate concentration in the lung. For expanded discussions of specific antibiotics, see Chapters 32 and e1.
A. Treatment of Outpatients
See Table 9-10. Recommended Empiric Antibiotics for Community-Acquired Bacterial Pneumonia for specific medication dosages. The most common etiologies of CAP in outpatients who do not require hospitalization are S pneumoniae; M pneumoniae; C pneumoniae; and respiratory viruses, including influenza. For previously healthy patients with no recent (90 days) use of antibiotics, the recommended treatment is amoxicillin, a macrolide (clarithromycin or azithromycin), or doxycycline. In areas with a high incidence of macrolide-resistant S pneumoniae, initial therapy in patients with no comorbidities may include the combination of a beta-lactam plus a macrolide, or a respiratory fluoroquinolone.
In outpatients with chronic heart, lung, liver, or kidney disease; diabetes mellitus; alcohol use disorder; malignancy; or asplenia or who received antibiotic therapy within the past 90 days, the recommended treatment is a macrolide or doxycycline plus a beta-lactam (high-dose amoxicillin and amoxicillin-clavulanate are preferred to cefpodoxime and cefuroxime) or monotherapy with a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin).
The default duration of antibiotic therapy for CAP should be 5 days; factors that may affect therapy duration are clinical stability, etiology (MRSA and P aeruginosa require 7 days of therapy, for example), severity of illness, complications, and comorbid medical problems.
B. Treatment of Hospitalized and ICU Patients
Almost all patients admitted to a hospital for treatment of CAP receive intravenous antibiotics. However, no studies in hospitalized patients demonstrated superior outcomes with intravenous antibiotics compared with oral antibiotics, provided patients were able to tolerate oral therapy and the medication was well absorbed. Duration of inpatient antibiotic treatment is the same as for outpatients.
The most common etiologies of CAP in patients who require admission to intensive care are S pneumoniae, Legionella species, H influenzae, Enterobacteriaceae species, S aureus, Pseudomonas species, and respiratory viruses. First-line antibacterial therapy in ICU patients with CAP is an anti-pneumococcal beta-lactam (cefotaxime, ceftriaxone, ceftaroline, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin).
Risk factors for Pseudomonas, Enterobacteriaceae, or MRSA infection must be considered when choosing empiric antibiotic therapy for inpatients with CAP. Specific risk factors for these organisms include (1) prior isolation of the pathogen, (2) inpatient hospitalization within the last 90 days, or (3) exposure to intravenous antibiotics within the last 90 days. In patients with specific risk factors for Pseudomonas infection, combine an anti-pneumococcal, anti-pseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, meropenem) with either azithromycin or a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin). In critically ill patients, in those at increased risk for drug resistance, or if the unit incidence of monotherapy-resistant Pseudomonas is greater than 10%, consider use of two agents with anti-pseudomonal efficacy: either ciprofloxacin or levofloxacin plus the above anti-pneumococcal, anti-pseudomonal beta-lactam or an anti-pneumococcal, anti-pseudomonal beta-lactam plus an aminoglycoside (gentamicin, tobramycin, amikacin) plus either azithromycin or a respiratory fluoroquinolone. Patients with specific risk factors for MRSA should be treated with vancomycin or linezolid. Patients with very severe disease (respiratory failure requiring mechanical ventilation or septic shock) should also be strongly considered for MRSA therapy. Provided the patient is clinically improving, negative sputum and blood cultures obtained prior to initiation of antibiotics can support de-escalation of antibiotic therapy. Additionally, all patients prescribed vancomycin or linezolid should have swabs of the nasal passages for MRSA; if the swab results are negative, MRSA coverage can be safely de-escalated, even when adequate sputum samples have not been obtained.
Patients with CAP in whom influenza is detected should be treated with the antiviral oseltamavir, whether influenza is identified as a single pathogen or as a coinfection along with a bacterial pathogen. Oseltamavir treatment is most effective when begun within 2 days but may still be beneficial within several days after symptom onset, particularly in severe cases of CAP.
Prevention
Pneumococcal vaccines prevent or lessen the severity of pneumococcal infections in immunocompetent patients. Two classes of pneumococcal vaccines for adults are available and approved for use in the United States: one containing capsular polysaccharide antigens to 23 common strains of S pneumoniae (PPSV23) and several polyconjugate vaccines, including 10-valent (PCV10), 13-valent (PCV13), 15-valent (PCV15), and 20-valent (PCV20). Updated recommendations are for either PCV20 alone, or sequential administration of PCV15 and PPSV23 in all adults aged 65 years or older, as well as adults with comorbidities (chronic lung disease, liver disease, or diabetes), increased risk of meningitis, asplenia, or immunocompromise. Some experts favor PCV20 followed by PPSV23 in patients at highest risk of invasive pneumococcal disease.
Many patients have already received a pneumococcal vaccine or a series of vaccines. Adults who have received only PPSV23 should receive PCV20. Adults who have received only PCV13 should receive PPSV23. Currently, healthy adults without comorbidities who have received both PCV13 and PPSV23 are not recommended to receive further vaccination with PCV20.
Immunocompromised patients and those at high risk of fatal pneumococcal infection should receive a single revaccination with PPSV23 5 years after the first vaccination, regardless of age, and revaccination with PPSV23 after age 65 (at least 5 years from the most recent dose of PPSV23).
The seasonal influenza vaccine is effective in preventing severe disease due to influenza virus with a resulting positive impact on both primary influenza pneumonia and secondary bacterial pneumonias. The seasonal influenza vaccine is recommended annually for all persons older than 6 months without contraindications, with priority given to persons at risk for complications of influenza infection (persons aged 50 years or older, immunocompromised persons, residents of long-term care facilities, patients with pulmonary or cardiovascular disorders, pregnant women) as well as health care workers and others who may transmit influenza to high-risk patients.
Vaccinations against SARS-CoV-2 are recommended for all adults without contraindications. Vaccinations (including boosters) reduce the likelihood of infection, pneumonia, hospitalization, and mortality (see COVID-19 discussion, Chapter 34).
Hospitalized patients who would benefit from pneumococcal and influenza vaccines should be vaccinated during hospitalization. The two vaccines may be administered simultaneously as soon as the patient has stabilized.
When to Admit
Once a diagnosis of CAP is made, the first management decision is to determine the site of care: Is it safe to treat the patient at home or does he or she require hospital or intensive care admission? There are two widely used clinical prediction rules available to guide admission and triage decisions, the Pneumonia Severity Index (PSI) and the CURB-65.
A. Hospital Admission Decision
The PSI is a validated prediction model that uses 20 items from demographics, medical history, physical examination, laboratory results, and imaging to stratify patients into five risk groups. In conjunction with clinical judgment, it facilitates safe decisions to treat CAP in the outpatient setting. An online PSI risk calculator is available at http://www.thecalculator.co/health/Pneumonia-Severity-Index-(PSI)-Calculator-977.html. The CURB-65 assesses five simple, independent predictors of increased mortality (Confusion, Uremia, Respiratory rate, Blood pressure, and age greater than 65) to calculate a 30-day predicted mortality (http://www.mdcalc.com/curb-65-score-pneumonia-severity). Compared with the PSI, the simpler CURB-65 is less discriminating at low mortality but excellent at identifying patients with high mortality who may benefit from ICU-level care. A modified version (CRB-65) dispenses with BUN and eliminates the need for laboratory testing.
Hospital admission decision should also include circumstances of care independent of pneumonia severity, including comorbidities and the patient's ability to care for themselves effectively at home.
B. ICU Admission Decision
Expert opinion has defined major and minor criteria to identify patients at high risk for death. Major criteria are septic shock with need for vasopressor support and respiratory failure with need for mechanical ventilation. Minor criteria are respiratory rate of 30 breaths or more per minute, hypoxemia (defined as PaO2/FIO2 equaling 250 or less), hypothermia (core temperature less than 36.0°C), hypotension requiring aggressive fluid resuscitation, confusion/disorientation, multilobar pulmonary opacities, leukopenia due to infection with WBC less than 4000/mcL (less than 4.0 × 109 /L), thrombocytopenia with platelet count less than 100,000/mcL (less than 100 × 109 /L), uremia with BUN of 20 mg/dL or more (7.1 mmol/L or more), metabolic acidosis, or elevated serum lactate level. Either one major criterion or three or more minor criteria of illness severity generally require ICU-level care.
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