Initial management strategies based on clinical setting of pneumonia
Greater emphasis on the cost-effective use of medical resources has spurred development of algorithms and guidelines for the clinician approaching common clinical problems. Pneumonia is a particularly good example of an important clinical problem for which such management strategies relating to both diagnostic evaluation and initiation of therapy have been developed. Importantly, even when rigorous diagnostic testing is pursued, the specific cause of pneumonia is frequently not identified, thus necessitating empiric treatment. In large studies done prior to the COVID-19 pandemic, the specific etiology of pneumonia in patients admitted to the hospital with pneumonia was identified in less than 40% of patients. When an etiology was found, respiratory viruses were the most common cause, accounting for approximately 25%. Specific bacterial causes were found in 13%, with S. pneumoniae accounting for over one-third of bacterial infections. It is likely that the proportion of organisms is different in the COVID-19 era. There is some early indication that the incidence of illness due to other respiratory viruses, including influenza, has decreased as the protective measures taken for COVID-19 (maskwearing and social distancing) also protect against transmission of other viruses.
Separate strategies are endorsed for two distinct groups of patients with pneumonia, depending on the setting where the pneumonia developed: (1) community-acquired pneumonia or (2) nosocomial (hospitalacquired) pneumonia. These guidelines apply to patients who do not have significant underlying impairment of systemic host defense mechanisms, such as patients with HIV/AIDS or those receiving immunosuppressive drugs or cancer chemotherapy.
Community-acquired pneumonia
Community-acquired pneumonia refers to pneumonia that develops in the community setting (i.e., in an individual who is not hospitalized). Although this category is not meant to include patients with significant impairment of systemic host defense mechanisms, it can include patients with other coexisting illnesses or risk factors that alter the profile of organisms likely to be responsible for pneumonia.
As noted above, because the cause of community-acquired pneumonia is never identified in more than 60% of patients, even after extensive testing, guidelines specify empiric antibiotic treatment. The recommended empiric therapy is determined by a number of modifying factors: the presence of coexisting illness, recent treatment with antibiotics, and the severity of illness at the initial presentation. If a specific pathogen is identified, the initial empiric antibiotic regimen is modified to avoid use of unnecessary antibiotics.
A presumptive diagnosis of pneumonia is made when the patient presents with signs and symptoms of a respiratory infection, and a chest radiograph confirms a pulmonary infiltrate. Fig. 23.5 summarizes the recommended initial approach to testing once a diagnosis of pneumonia is made. All patients should be tested for SARS CoV-2 and seasonally for influenza. The next steps are assessing for comorbidities and establishing the severity of illness, which determines whether the patient requires hospital admission or can be treated as an outpatient. A number of scoring systems have been developed to assess the need for hospitalization or ICU admission for an individual patient based on demographic characteristics and the severity of the illness at presentation. A detailed discussion of these algorithms is beyond the scope of this chapter, but references to the most common management algorithms are provided. Further testing and treatment are based on specific subcategories of patients specified by these algorithms.
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FIGURE 23.5 Approach to diagnostic testing for community-acquired pneumonia.
CAP, community-acquired pneumonia; MRSA, methicillin-resistant Staphylococcus
aureus; PCR, polymerase chain reaction. Source: (Recommendations are adapted
from Jones, B. E., Herman, D. D., Dela Cruz, C. S., Waterer, G. W., Metlay, J. P.,
Ruminjo, J. K., et al. (2020). Summary for clinicians: Clinical practice guideline for
the diagnosis and treatment of community-acquired pneumonia. Annals of the
American Thoracic Society, 17, 133–138.)
Importantly, each patient must be considered on an individual basis, and the recommendations are intended as guidelines to help with decision-making rather than as strict rules. One important aspect of empiric treatment is the need for careful follow-up. Most patients respond to treatment within 48 to 72 hours. If a patient does not respond within this time frame, reassessment with consideration of a change in therapy is indicated.
The first group of patients with community-acquired pneumonia who are specified in guidelines are those who do not have coexisting cardiopulmonary disease or other modifying factors, and who do not require hospitalization. The most common pathogens in this group of patients include S. pneumoniae, M. pneumoniae, C. pneumoniae, respiratory viruses, and in smokers, H. influenzae. The most widely accepted therapeutic regimens are monotherapy with either amoxicillin or doxycycline. A macrolide, such as azithromycin or clarithromycin, should be used only in areas where the incidence of pneumococcal resistance to macrolides is less than 25%. Unfortunately, this excludes the United States and many other countries. An issue with using amoxicillin as monotherapy in this population is that amoxicillin does not treat either Mycoplasma or Chlamydophila pneumonia, which are common pathogens, and has led some authorities to recommend both amoxicillin and a macrolide, or doxycycline alone as initial therapy in this population.
In community-acquired pneumonia, factors influencing the likelihood of certain organisms and therefore the therapeutic approach include age, the presence of coexisting illness, and the severity of pneumonia at the initial presentation.
The second group includes patients who have coexisting cardiopulmonary disease or other modifying risk factors but still can be treated in an outpatient setting. Important comorbidities that place a patient in this category include chronic heart, lung, liver, or kidney disease; diabetes mellitus; alcohol use disorder; malignancies; asplenia; immunosuppressive conditions or drugs; or the use of antibiotics within the prior 3 months (in which case antibiotics from a different class should be used). Again, local resistance patterns of S. pneumoniae should be taken into account, and residence in a nursing home or other healthcare facility should be considered a factor that increases the risk of pneumonia caused by a Gramnegative organism. Poor dentition (leading to an increased burden of anaerobic organisms in the mouth), problems with swallowing, or impaired consciousness increase the risk of an anaerobic aspiration pneumonia. Recommended options for management of patients with comorbidities include a β-lactam antibiotic (e.g., amoxicillin/clavulanic acid or cefuroxime) given in combination with a macrolide (particularly an advanced-generation macrolide, e.g., azithromycin or clarithromycin) or doxycycline, or monotherapy with an oral respiratory quinolone (e.g., levofloxacin, moxifloxacin).
The third and fourth groups differ from the first two on the basis of severity of the pneumonia. The third group is defined by a need for hospitalization. The fourth group includes patients with the most severe disease, which usually necessitates admission to an intensive care unit (ICU). These patients still commonly have pneumonia caused by S. pneumoniae or the other organisms found in outpatients, but with additional concern for Gram-negative bacilli, Legionella, and sometimes S. aureus, including MRSA. Therapy for these patients is adjusted accordingly. Recommended antibiotic regimens include a β-lactam antibiotic plus a macrolide or a respiratory fluoroquinolone. If there is concern for MRSA, vancomycin typically is added. If there is a history of documented Pseudomonas infection within the past year, then anti-Pseudomonas treatment is included.
There are some data to suggest that adjunctive treatment with corticosteroids may be beneficial in patients with severe pneumonia. However, this practice has not been uniformly adopted, and some data suggest that patients with pulmonary infection due to influenza or Aspergillus may have worse outcomes if corticosteroids are used. Currently, the routine use of corticosteroids in patients with severe pneumonia is not recommended except when it is due to COVID-19, a situation where corticosteroids appear to improve outcomes in patients with severe disease.
Further diagnostic testing
As noted, all patients presenting with community-acquired pneumonia should be tested for SARS-CoV-2 and seasonally for influenza. Additional diagnostic testing is reserved for patients with pneumonia requiring hospital admission. Among outpatients with community-acquired pneumonia, extensive testing adds significant cost, does not change treatment or outcomes, and usually does not result in a specific diagnosis. Here we describe the general guidelines for further diagnostic testing of inpatients with community-acquired pneumonia, but recognize that clinical decisions must be based on the individual patient.
Routine testing with Gram stain and culture of lower respiratory specimens was previously the standard of care for patients with pneumonia. It is now recognized that these tests are of low yield and typically do not affect treatment decisions or outcome. Thus, sputum testing is only recommended in patients admitted to the hospital. Similarly, routine blood cultures are also recommended only for hospitalized patients with community-acquired pneumonia unless MRSA or Pseudomonas aeruginosa is
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suspected. When a sputum specimen is obtained, it is important to evaluate the quality of the specimen, because a poor quality specimen may provide inadequate or inaccurate information. In an appropriate sputum specimen (i.e., one that contains few squamous epithelial cells picked up in transit through the oropharynx), inflammatory cells and bacteria can be seen.
In most bacterial pneumonias, large numbers of PMNs are seen in the sputum. In contrast, mycoplasmal and viral pneumonias have fewer PMNs and more mononuclear inflammatory cells. Pneumococcal, staphylococcal, and Gram-negative bacillary pneumonias commonly demonstrate a relatively homogeneous population of the infecting bacteria. Anaerobic aspiration pneumonias, caused by a mixture of organisms from the oropharynx, show a mixed population of bacteria of many different morphologies. In Legionnaires disease, the bacterium does not stain well with the usual Gram stain reagent, and visualization requires special stains. In mycoplasmal and viral pneumonia, the infecting agent is not detected on light microscopy, and only the predominantly mononuclear cell inflammatory response is seen.
When sputum is not spontaneously expectorated by the patient, other methods for obtaining respiratory secretions (or even material directly from the lung parenchyma) may be necessary. Techniques that can be used—flexible bronchoscopy, needle aspiration of the lung, and surgical lung biopsy—are described in greater detail in Chapter 3. Further recommendations for patients admitted to the hospital with severe pneumonia include urinary antigen testing for S. pneumoniae and Legionella as well as specialized respiratory cultures for Legionella species.
Nosocomial (hospital-acquired) pneumonia
In contrast to community-acquired pneumonia, nosocomial pneumonia is defined as pneumonia which develops in a hospital setting. Nosocomial pneumonia, also called hospital-acquired pneumonia, is defined as a pneumonia that occurred 48 hours or more after admission and did not appear to be developing at the time of presentation. Patients in ICUs, especially those receiving mechanical ventilation, are at particularly high risk for developing this category of pneumonia. When a patient develops a new pneumonia 48 hours or more after endotracheal intubation, the patient is considered to have a ventilator-associated pneumonia, which is a subset of hospital-acquired pneumonia.
The primary route of infection for both hospital-acquired pneumonia and ventilator-associated pneumonia is microaspiration of organisms from the oropharynx into the tracheobronchial tree. The hospital environment and treatment with antibiotics lead to a change in the normal oropharyngeal flora; thus, the organisms associated with hospital-acquired pneumonia are different from those commonly causing community-acquired pneumonia. Patients at risk often have other underlying medical problems, have been receiving antibiotics, or have an endotracheal tube in their airway that bypasses some of the normal protective mechanisms of the respiratory tract. Gastric acid–reducing medications, particularly proton-pump inhibitors, have been implicated as a risk factor for nosocomial pneumonia in some studies; an increase in gastric pH allowing increased bacterial growth is the presumed mechanism. Contamination of the apparatus for respiratory support, including tubing and humidification reservoirs, is also implicated.
Organisms of particular concern in nosocomial pneumonia include Staphylococcus aureus, Gramnegative bacilli, and Legionella.
Organisms of particular concern in patients who develop hospital-acquired pneumonia are Gramnegative bacilli (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Grampositive cocci (S. aureus, including MRSA), but other organisms such as respiratory viruses and