Pneumonia is an acute inflammatory condition within the parenchyma of the lung caused by infection that reaches the lower respiratory tract. In most cases, pneumonia develops as a consequence of bacterial colonization/infection of the upper respiratory tract, followed by microaspiration of infected secretions at a time of impaired host pulmonary defense mechanisms [217]. The prime host defenses against foreign particulate matter that reaches the lower respiratory tract are the cough reflex, tracheobronchial (mucociliary) clearance, and alveolar macrophage phagocytosis. Activation of the humeral (antibody) immune response provides augmentation of phagocytosis and the acute cellular response. One or more of these defense mechanisms may be impaired by a variety of factors, including underlying cardiopulmonary and neurologic disease, sedative medication, bronchial obstruction, concurrent active viral and mycoplasma bronchitis, and toxic/metabolic conditions such as alcohol excess, acidosis, and hypoxia. Individuals with an impaired immune system, such as occurs from immunosuppressive drugs, human immunodeficiency virus (HIV), chronic disease, or old age, are more susceptible to infection [4].

Clinically, pneumonia is often described in reference to suspected or established causative pathogens (i.e., viral, bacterial, fungal, or parasitic); however, the precise etiology cannot be identified in more than half the cases in which testing is done [9,24,25]. Classifying pneumonia according to setting in which it develops is more useful for clinical purposes because the most common pathogens, as well as clinical outcomes, are similar within distinct clinical settings [26,27]. Pneumonia was once broadly classified as either community-acquired (developing outside of a hospital or other healthcare facility) or nosocomial (developing 48 hours or more after hospital admission, usually postoperatively). In its 2016 guideline, the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) noted three distinct categories within the broader classification of pneumonia associated with healthcare facilities: HAP, VAP, and HCAP (Table 2) [3,28]. These three categories of pneumonia are similar in that they often result from colonization, then infection, by resistant gram-negative bacilli and methicillin-resistant Staphylococcus aureus (MRSA), necessitating broader empiric antibiotic therapy than that commonly used for CAP [27].

Determining accurate incidence rates for CAP is challenging because "pneumonia" is not a reportable disease; moreover, case definition varies across studies and national databases often link pneumonia with influenza. Epidemiology of pneumonia relies primarily on data derived from community-based cohort studies and surveillance networks. Approximately 5 to 6 million cases of pneumonia are diagnosed annually, with about 1 million occurring in older adults [36]. Approximately 4.2 million adult outpatient visits are related to CAP every year, and the mortality rate is less than 1% for adults treated on an outpatient basis [37].

The primary risk factors for CAP are age, smoking history, and chronic lung disease (e.g., chronic obstructive pulmonary disease [COPD]) and other comorbidities. Occupational dust exposure and history of childhood pneumonia have also been associated with an increased risk, as has male gender, unemployment, and single marital status [39,41]. As noted earlier, the risk for pneumonia is higher for individuals 65 years or older compared with younger adults, with the risk further increasing for those 85 years and older [39]. Alcoholism and chronic diseases, such as respiratory disease, cardiovascular disease, or kidney disease, also increase the risk for pneumonia, especially in the older population [3,42,43]. Conditions of frailty, dementia, alcohol use, and sedative medication all lead to diminished or ineffectual cough and the propensity for aspiration, thereby increasing the risk for pneumonia. Diseases or medications that suppress the immune system increase the risk among all ages [39,42]. In the pediatric population, very young children are at increased risk because their immune systems have not fully developed. Secondhand smoke exposure, particularly with two or more smokers in the home, is a significant risk factor for pneumonia in children [241].

The most common cause of CAP is S. pneumoniae, identified in approximately one-third of all cases and 40% to 50% of all culture-confirmed bacterial pneumonia cases that require hospitalization [9,29,30,46]. The most common causative pathogen varies in relation to the patient's age, illness severity, and clinical context (Table 3) [29,30,47].

Mixed viral-bacterial infection has been documented in 30% of adult cases of CAP in some studies [9,31,34]. S. pneumoniae in combination with rhinovirus, influenza A, or RSV is found most commonly [34]. On rare occasions fungal and parasitic pathogens are isolated in association with CAP syndrome.

The clinical recognition of CAP in adults is challenging because its presentation is similar to other acute respiratory illnesses such as pulmonary embolism/infarction and congestive heart failure [3,51,52]. Diagnosis relies on clinical features combined with radiographic findings; however, both the clinical presentation and chest x-ray abnormalities are variable and in part nonspecific, particularly in the elderly [3,29]. Common presenting symptoms and signs are:

Viral culture remains the criterion standard for diagnosis of viral pneumonia, but because of limitations such as the need for prompt transportation, time needed for viral detection, and the lack of sensitivity for all viruses, rapid antigen testing is often done. In adults, rapid testing has a sensitivity of 50% to 60% and a specificity of at least 90% [31]. Testing of nasal swab specimens is slightly less sensitive than testing of wash specimens, but wash specimens can be difficult to obtain in frail or cognitively impaired adults. Rapid RSV tests are usually not useful for adults, as the level of virus titers shed is low [31]. Diagnostic testing (PCR) for SARS-CoV-2 by nasopharyngeal swab may be performed on patients presenting with CAP in areas experiencing COVID-19 epidemic activity, although lower respiratory symptoms typically begin as upper respiratory symptoms are resolving or have already resolved.

It is estimated that admission to an ICU is needed for 10% to 20% of patients hospitalized with CAP [76]. The IDSA/ATS guideline recommends two major and nine minor criteria to define severe pneumonia requiring ICU admission. [47]. The major criteria are septic shock requiring vasopressors or acute respiratory failure requiring intubation and mechanical ventilation. The presence of at least three of the following minor criteria suggests the need for ICU admission [47]:

Pending results of cultures and serologic testing, an initial empiric treatment regimen is selected according to patient variables and clinical setting (Table 6) [47]. Patients with mild illness and no serious coexisting disease may be managed as outpatients. The 2019 ATS/IDSA guideline recommends amoxicillin 1 g three times daily, doxycycline 100 mg twice daily, or a macrolide (e.g., azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily) [235]. The macrolide monotherapy recommendation is conditional based on prevalence of local pneumococcal resistance (<25%) and provided the patient has not received antimicrobials within the previous three months [47]. S. pneumoniae resistance to macrolides is four times more likely in adult patients who have received this class of drug within the previous three months, in which case a fluoroquinolone or ß-lactam plus macrolide combination should be selected. Patients with comorbidities should receive broader spectrum treatment as they are more likely to harbor resistant pathogens and to be more vulnerable to poor outcomes if the initial regimen is inadequate. For outpatient adults with comorbidities, the ATS/IDSA guideline recommends one of the following options (in no order of preference) [235]:

Viral pathogens are reported to be responsible for most cases of CAP in preschool-aged children and as many as 80% of cases in children younger than 2 years of age [30]. In children younger than 2 years of age, the most common viral pathogen, occurring in up to 40% of cases, is RSV; other viral pathogens include adenoviruses, bocavirus, human metapneumovirus, influenza A and B viruses, parainfluenza viruses, coronaviruses, and rhinovirus [9,29,30,32].

RSV infection is common in infants and young children; it is estimated that most children have had RSV by 2 years of age [31]. It is the leading cause of pneumonia in infants younger than 1 year of age, with 25% to 40% of those infected developing signs of pneumonia or bronchiolitis [29]. Premature birth, very young age, compromised immune system, and impaired lung or heart function are all risk factors for RSV-related pneumonia in infants. In contrast to preschool-aged children, the percentage of viral cases is much lower among older children and adolescents (10 to 16 years of age), and pneumonia caused by RSV is rare in this population.

During the physical examination of pediatric patients, the clinician should look for signs of hypoxia and dehydration, as well as retractions, tachypnea, and use of accessory muscles of respiration [60]. The clinician should also evaluate the upper respiratory tract for evidence of rhinorrhea, otitis media, and pharyngitis [60]. Auscultation of the chest should be carried out, and the Pediatric Infectious Diseases Society (PIDS)/IDSA guideline recommends pulse oximetry for children with suspected hypoxemia [30].

One of the most common reasons for pediatric emergency room visits is fever, and fever is present in 88% to 96% of identified pneumonia cases in developed countries [70]. However, children with fever and wheezing commonly have either upper respiratory disease or reactive airway disease. As with pneumonia in adults, the accuracy of any one sign or symptom in predicting the likelihood of pneumonia is limited [61]. Nonspecific symptoms such as vomiting and abdominal discomfort are common. Careful attention should be given to the chest exam, as diminished breath sounds and fine end-inspiratory crackles are subtle, important clues to the presence of pneumonia in the pediatric patient. In one study, non-specific crackles were present in more than 90% of children with pneumococcal or mycoplasma pneumonia [70]. Infants with pneumonia commonly present with poor feeding and irritability as well as tachypnea, retractions, grunting, and hypoxemia; cough is rare [64].

Unlike the situation in adults, titers of shed virus in children are high [31]. Thus, rapid antigen testing of nasal or throat swabs for influenza and other respiratory viruses should be done for infants and young children [30]. However, it should be noted that negative results of influenza virus on rapid antigen tests do not conclusively rule out infection with influenza virus. Testing for C. pneumoniae is not recommended.

Blood cultures are not routinely needed but should be obtained in children hospitalized for moderate-to-severe pneumonia that is presumed to be bacterial [30]. Urinary antigen detection tests often have false-positive results in children and are therefore not recommended for the diagnosis of pneumococcal pneumonia.

To aid in making site-of-care decisions, the PIDS/IDSA guidelines recommend that a child or infant with CAP be hospitalized if any of the following factors are present [30]:

Most children with pneumonia do not require care in an ICU. The guideline states that a child should be admitted to an ICU or a unit with continuous cardiorespiratory monitoring capabilities if the child [30]:

For fully immunized infants and school-aged children who are hospitalized, treatment with ampicillin or penicillin G is recommended when local epidemiologic data show a low level of penicillin resistance to S. pneumoniae [30]. For children who are not fully immunized or are hospitalized in an area with a high level of penicillin-resistant S. pneumoniae, treatment with a third-generation cephalosporin (ceftriaxone or cefotaxime) should be given intravenously. If M. pneumoniae or C. pneumoniae is strongly suspected, treatment should include a macrolide (orally or intravenously) with a ß-lactam and diagnostic testing should be done as soon as possible [30]. The PIDS/IDSA guideline also recommends antimicrobial treatment for specific pathogens; however, a discussion of all possible pathogens is beyond the scope of this course.

The primary preventive strategy for pneumonia is immunization with pneumococcal and influenza vaccines, especially for adults older than 65 years of age, young children, and other individuals in high-risk groups (Table 9) [91]. Additional preventive measures include improved hand hygiene compliance and adherence to healthy lifestyle behaviors, including cigarette smoking cessation.

In 2018, the estimated overall rate of pneumococcal vaccination coverage among adults older than 65 years of age was 69% [237]. The rate was substantially lower (approximately 23%) among younger adults in high-risk groups. Selected data from this report are summarized in Table 12[237].

In its Healthy People 2030 initiative, the U.S. Department of Health and Human Services has set objectives for improving vaccination rates among adults and children [114]. To reach these targets, healthcare providers must address documented barriers to recommended vaccinations and gain a better understanding of other challenges to vaccination. Unequal access to health care appears to account for a low percent of racial disparities [105]. Rather, lack of awareness of the need for vaccination and misconceptions about vaccines have been reported as the primary barriers in several studies [104,105,106,115,116,117].

Parental attitudes about vaccines are an important factor in vaccination rates among children. The primary attitude is concern about the safety and efficacy of the vaccine, including fear of adverse events, the discomfort associated with vaccination, distrust of advocates of vaccination, and belief that the vaccine should not be given when a child has a minor illness [117,120,121,122]. Difficulty remembering or confusion about the vaccination schedule for children is also a major challenge [120,122]. Changes in access to health care have been noted as a factor in the low rate of influenza vaccination among teenagers [117].

Approximately 3 to 10 cases of HAP occur per 1,000 hospital admissions [26]. Pneumonia as a complication of hospitalization increases length of stay (by more than one week), increases mortality risk, and adds an additional cost of care that can reach $40,000 per case [26].

In a systematic review, the American College of Physicians found several patient-related and surgery-related factors that increased the risk of postoperative pulmonary complications. The most common patient-related factors were the presence of COPD and an age older than 60 years [145]. Other significant factors were an American Society of Anesthesiologists (ASA) class of 2 (defined as a patient with mild systemic disease) or higher, functional dependence, and congestive heart failure. Cigarette use was associated with a modest increase in risk, and obesity and mild or moderate asthma were not found to increase risk [145]. Use of a PPI or histamine2 receptor antagonist is also thought to be a risk factor [45]. Surgery-related factors included prolonged duration of surgery (i.e., more than three to four hours), emergency surgery, and surgical site, with abdominal surgery, thoracic surgery, neurosurgery, head and neck surgery, vascular surgery, and aortic aneurysm repair being associated with the greatest risks [145].

The risk for VAP appears to be greatest during the first week after intubation. In one study, the risk was estimated to be 3% per day during the five-day period following intubation, decreasing to 2% per day for days 5 through 10, and to 1% per day for longer durations [147]. In a population of children who had cardiothoracic surgery, pneumonia risk correlated with mechanical ventilation for longer than three days [144]. Nearly half of all cases of VAP develop within the first four days of mechanical ventilation [148].

Viral and fungal pathogens are rare causes of HAP, VAP, and nursing home-acquired pneumonia in immunocompetent adults. Outbreaks of viral pneumonia may occur during influenza season, and influenza, parainfluenza, adenovirus, and RSV are involved in about 70% of those cases [28]. Candida spp. and Aspergillus fumigatus may cause pneumonia in patients who have had organ transplantation or who have a compromised immune system and neutropenia.

The bacterial pathogens that cause pneumonia in residents of nursing homes (and other long-term care facilities) differ according to the severity of disease. S. pneumoniae and H. influenzae are the most common causes of mild-to-moderate pneumonia in long-term care facilities [155]. In cases requiring hospitalization, C. pneumoniae, S. aureus, and influenza virus are frequently observed as well. Patients with severe illness commonly are infected with methicillin-sensitive S. aureus or MRSA, gram-negative enteric pathogens, or P. aeruginosa [23,155].

In managing a case of HAP and VAP, the clinician should review in detail the guidance provided by the ATS/IDSA, and consider consultation with appropriate subspecialty colleagues [28]. Recommendations governing selected issues of initial management emphasize the following principles [28]:

Smoking triples the risk for pulmonary complications after surgery, and smoking cessation for at least eight weeks before surgery, when possible, is recommended for current smokers [26]. The risk for complications in patients with respiratory disease or congestive heart failure can be ameliorated by optimum treatment before surgery (e.g., treatment with steroids for patients with COPD or asthma) [26].

The Institute for Healthcare Improvement (IHI) found that implementation of its ventilator bundle, a collection of five prevention strategies drawn from these guidelines, led to a 45% reduction in the incidence of VAP [174]. The bundle includes the following interventions [174]:

Reducing the risk of aspiration and contamination with gastric secretions also helps to prevent the development of pneumonia. Positioning the head of the bed at an angle of 30 to 45 degrees reduces the risk of aspiration significantly [149,178,179]. In one randomized, controlled trial, there were 18% fewer cases of VAP among intubated patients in the group assigned to the recumbent position (45 degrees) compared with the group assigned to the supine position [179]. In another study, elevation of the head of the bed to 30 degrees was the most effective measure among a group of preventive interventions, resulting in a 52% variance in the rate of VAP [180]. Both the ATS/IDSA and SHEA/IDSA guidelines recommend maintaining the head of the bed at a 30- to 45-degree angle [28,171]. An angle of 30 to 45 degrees is also recommended for infants and children, but a lower angle (15 to 30 degrees) should be used for neonates [177].

As with HAP, strategies to decrease or eliminate modifiable risk factors for nursing home-acquired pneumonia should be implemented. A multidisciplinary panel made three recommendations for prevention of pneumonia among nursing home residents [199]:

Despite the simplicity of the intervention, its substantial impact, and wide dissemination of the guideline, compliance with recommended hand hygiene has ranged from 16% to 81%, with an average of 30% to 50% [207,208,209,210,211,212]. Among the reasons given for the lack of compliance are inconvenience, understaffing, and damage to skin [207,210,213]. The development of effective alcohol-based handrub solutions addresses these concerns, and studies have demonstrated that these solutions have increased compliance [211,214,215]. The CDC guideline recommends the use of such solutions on the basis of several advantages, including [207]: