Introduction and Epidemiology
CAP is one of the most frequent causes of infection-related death in the United States. It occurs in approximately 4 million adults per year, accounting for 1.1 million hospitalizations and 50,000 deaths per year. Of the 20% to 60% of patients who require hospital admission for CAP, anywhere between 10% and 22% may require critical care.1 Mortality rates remain high despite advances in antibiotics and critical care.
The lower respiratory tract remains sterile because of a combination of pulmonary defense mechanisms that involve anatomic and mechanical barriers, and humoral and cell-mediated immunity. The development of CAP is therefore a result of either a defect in the host pulmonary defense system, an exposure to a virulent or large inoculum of microorganisms, or a combination of these factors.2 Certain risk factors for CAP have previously been described. These include increased age, male sex, malnutrition or poor dental hygiene, high alcohol consumption, smoking, immunosuppression including HIV, asplenia, and other underlying comorbidities.3
The most common etiology of CAP remains bacterial or viral; other fungal or parasitic organisms are isolated infrequently and are usually related to various geographic and host factors. Causes of bacterial CAP can be divided into typical or atypical organisms. The most common cause of CAP is Streptococcus pneumoniae; other typical bacterial pathogens include Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and gram-negative organisms such as Klebsiella pneumoniae and Pseudomonas aeruginosa, seen in patients with previous exposure to antimicrobials or structural lung disease. Community-associated methicillin-resistant S aureus (CA-MRSA) as an etiology of CAP should be considered in the appropriate clinical situation, usually in patients presenting with cavitary pneumonia, lung necrosis, or concurrent influenza.4 Atypical organisms, such as Mycoplasma pneumoniae, Chlamydophila spp. (Chlamydophila pneumoniae and Chlamydophila psittaci), and Legionella, can often result in admission to the ICU. Viral etiologies should not be overlooked and include influenza and respiratory syncytial virus; other viruses such as parainfluenza, human metapneumovirus, and adenovirus should also be considered. Influenza specifically should be included in the differential of anyone presenting with CAP in the typical season, especially given that a significant number of patients can have concomitant bacterial infection. Other pathogens in the appropriate host include Mycobacterium tuberculosis, specifically in patients who are homeless, recently incarcerated, have HIV, or are from a country where tuberculosis is considered prevalent. Endemic fungi such as Histoplasma capsulatum, Coccidioides immitis, and Blastocystis hominis should be considered in patients from the appropriate geographic region. Immunocompromised hosts, such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with HIV/AIDS, and patients on chemotherapy may be at risk for other opportunistic pathogens such as Aspergillus, Cryptococcus, and Pneumocystis jiroveci pneumonia.
CAP is defined as acute infection of the lungs in patients who are not hospitalized or residents of long-term care facilities. Patients can present with symptoms of cough, fever, dyspnea, sputum production, and pleuritic chest pain. Other nonrespiratory symptoms may also be present. On physical examination, vital signs are notable for fever and associated tachycardia; hypotension is also present in severe CAP and concomitant septic shock. Tachypnea, the use of accessory muscles, or cyanosis and hypoxia are seen in respiratory compromise. Rales, bronchial breath sounds, and egophony are present on auscultation. On laboratory examination, leukocytosis with neutrophilic predominance is typically seen, although leukopenia can also occur in septic shock. Other signs of organ dysfunction such as acute kidney injury, hepatic dysfunction, lactic acidosis, and disseminated intravascular coagulation can also be seen with severe CAP and concomitant sepsis.
A chest radiograph should be performed and is critical to differentiating between upper respiratory and lower respiratory tract infection. Typically, a lobar infiltrate is present in bacterial pneumonia such as those seen in pneumococcal pneumonia; an interstitial pattern is typically seen with Mycoplasma and a bilateral mixed interstitial-alveolar pattern can be seen in viral pneumonia.2 For patients hospitalized with suspected CAP but a negative chest x-ray, occasionally an infiltrate can be seen when the chest x-ray is repeated in 24 to 48 hours.5 Computed tomography (CT) of the chest is not routinely recommended given radiation exposure and expense; however, it may be useful in certain situations, such as nonresponse to initial therapy or in the immunocompromised host where certain infections such as Aspergillus and M tuberculosis have a classic appearance.2
In patients admitted to the ICU, certain diagnostic tests are recommended by Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines. All patients with severe CAP should have blood cultures done to guide antibiotic therapy. In addition, urinary antigens for Legionella pneumophila and S pneumoniae should be performed. These may be especially useful in pneumococcal pneumonia when initial antibiotics have been given and the utility of a positive blood culture may be reduced. In Legionella, culture is less sensitive and urinary antigen testing is a useful tool for diagnosis, although only positive in serogroup 1. In addition, rapid antigen or PCR testing for viruses such as influenza should be performed in the appropriate clinical setting. If expectorated sputum of good quality with minimal oropharyngeal contamination can be obtained, it should be sent for Gram stain and culture. In intubated patients with severe CAP, endotracheal aspirates or bronchoscopy can be done to obtain respiratory samples for culture, with significantly more yield.5
For each patient being evaluated for pneumonia, the following 2 questions need to be asked—“Should the patient be hospitalized?” and if so, “Should the patient be admitted to the ICU?” Several scoring systems have been developed to assess severity of illness in order to identify patients with severe CAP. The first 2 tools, the Pneumonia Severity Index (PSI) and CURB-65, can aid in the diagnostic decision of whether or not to admit someone to the hospital. The PSI, which has been validated in several large studies, uses age, comorbidity, and vital signs to determine if the patient can be discharged and treated as an outpatient. The second tool, the British Thoracic Society CURB-65 system, uses fewer variables—confusion, urea, respiratory rate, blood pressure (BP), and age, to determine if patients can be treated as an outpatient or should be admitted.6
In addition, the IDSA/ATS has developed criteria to aid in identifying patients that would require admission to the ICU (Table 39–1). Any patient with one of the major criteria, either vasopressor use or respiratory failure requiring intubation and mechanical ventilation, require admission to the ICU. Patients with 3 of the minor criteria should also be considered for direct admission to an ICU.
Table 39–1Criteria for severe community-acquired pneumonia. ||Download (.pdf) Table 39–1 Criteria for severe community-acquired pneumonia.
|Major Criteria ||Minor Criteria |
|Septic shock requiring vasopressors ||Respiratory rate ≥ 30 breaths/min |
|Acute respiratory failure requiring intubation and mechanical ventilation ||PaO2/FIO2 ratio ≤ 250 |
| ||Multilobar infiltrates |
| ||Confusion/disorientation |
| ||Uremia (BUN level ≥ 20 mg/dL) |
| ||Leukopenia (WBC count < 4000 cells/mm3) |
| ||Thrombocytopenia (platelet count < 100,000 cells/mm3) |
| ||Hypothermia (core temperature < 36°C) |
| ||Hypotension requiring aggressive fluid resuscitation |
Validation studies support the use of the criteria in Table 39–1. Other scoring systems have been developed and include the SMART-COP, which aims to predict the need for respiratory or vasopressor support and the PIRO score, which aims to predict 28-day mortality.1
The initial treatment for CAP is empiric therapy directed at the most common pathogens; specific risk factors based on the host as well as local hospital epidemiology should be taken into account when considering initial therapy. For patients admitted to the ICU with severe CAP, a beta-lactam for initial pneumococcal coverage and plus either azithromycin or a respiratory fluoroquinolone for atypical coverage is recommended. In patients with a severe penicillin allergy, a respiratory fluoroquinolone or aztreonam is recommended. If Pseudomonas is suspected based on risk factors such as structural lung disease in bronchiectasis or severe chronic obstructive pulmonary disease (COPD) with frequent steroid or antibiotic use, then an antipseudomonal beta-lactam is recommended (ie, cefepime, piperacillin-tazobactam or a carbapenem).
Drug-resistant pneumococcus has been reported, with about 85% of isolates susceptible to penicillin and up to 30% of isolates demonstrating resistance to macrolides.1 Respiratory fluoroquinolone resistance remains low in North America. In cases where CA-MRSA is suspected, such as necrotizing pneumonia or lung abscess, linezolid or vancomycin should be added.5 In one randomized control trial for nosocomial pneumonia, linezolid has been shown to have clinical superiority to vancomycin although there was no difference in 60-day mortality.7 It is unclear if this data can be generalized to patients with CAP. Ceftaroline, which has activity against MRSA in addition to other gram-positive and gram-negative pathogens, was approved for the treatment of CAP based on phase III trials which demonstrated noninferiority to ceftriaxone for the treatment of non-ICU hospitalized CAP.8 Telavancin, a new gram-positive agent, which has activity against MRSA, has also been approved for hospital-acquired pneumonia.9 Daptomcyin is not effective in the treatment of MRSA pneumonia because it is inactivated by surfactant.
Antimicrobial therapy should be administered in the emergency department as quickly as possible in order to avoid delayed treatment, which has been associated with adverse outcomes. If a microbiological etiology is identified, treatment should be narrowed appropriately. In general, patients with CAP should be treated for at least 5 days,5 with the majority receiving around 7 to 10 days for severe CAP. Treatment can be continued with oral therapy once there has been clinical improvement. While studies on duration of therapy are generally limited, a randomized controlled trial looking at duration of therapy for ventilator-associated pneumonia (VAP) showed that 8 days of therapy were as effective as 15 days of therapy.10