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Introduction   

Pneumonia is an acute respiratory disease diagnosed in patients of all ages and populations. Individuals with comorbidities or in specific age groups are at an increased risk of developing pneumonia. There are varying symptoms of pneumonia, including an atypical presentation, which can make diagnosing pneumonia sometimes difficult. Therefore, healthcare providers must understand the typical and atypical symptoms of pneumonia, along with potential differentials and overlapping health conditions. The purpose of this course is to equip learners with the knowledge and expertise related to pneumonia. It reviewed the statistical evidence, pathophysiology, and etiology of pneumonia. Readers will also read about advanced health assessment practices and diagnostics reasoning to help determine the likelihood of possible differential diagnoses. Lastly, pharmacological treatment and follow-up monitoring of patients with pneumonia are discussed.

Definitions 

• Community-acquired pneumonia (CAP): Pneumonia developed outside of a hospital. This includes health centers, nursing homes, rehabilitation, assisted living, skilled nursing facilities [8, 11]. 

• Hospital-acquired pneumonia (HAP): Pneumonia developed within a hospital setting. Diagnosis must be made 48 hours after admission, and symptoms were not present during the time of admission [8]. 

• Ventilator-associated pneumonia (VAP): Pneumonia that develops after endotracheal intubation within 48 hours [8]. 

• Atypical pneumonia: Sometimes also called “walking pneumonia,” where symptoms are not typical and tend to be milder. Identified pathogens are not the common causes [8]. 

Statistical Evidence 

Pneumonia impacts individuals of all ages and populations. The World Health Organization reports that pneumonia is the “single largest infectious cause of death in children worldwide.” In 2019, pneumonia accounted for about 14% and 22% of deaths in children under 5 years of age and between 1 and 5 years old, respectively. Additionally, children living in southern Asia or sub-Saharan Africa are more likely to die from pneumonia [15]. 

The Centers for Disease Control and Prevention (CDC) estimates that around 1.4 million are diagnosed with pneumonia in the U.S. annually, with most visits occurring in the emergency room. Furthermore, just over 41,000 Americans die annually from pneumonia, which equates to about 12.3 deaths per 100,000 people [1].  

According to the CDC, influenza and pneumonia were ranked as the 9th and 13th leading causes of death in the United States for 2020 and 2021, respectively [2]. Furthermore, preliminary 2023 estimates for the U.S. show that influenza and pneumonia rank as the 11th leading causes of death, accounting for approximately 13.5% of deaths per 100,000 [3]. 

Pathophysiology 

While the respiratory tract's primary responsibility is to exchange oxygen and carbon dioxide, it also helps filter bacteria and other potentially harmful pathogens from entering the body. Similar to other body systems, like the gastrointestinal tract and integumentary system, the respiratory system has a balance of organisms and immune defenses, both innate and acquired. When there’s a breakdown in the body’s natural defenses, pathogens can enter the lung alveoli, and immune macrophages respond and attempt to clear the new pathogen. The macrophages signal to other molecules and cytokines, triggering an inflammatory response. By signaling neutrophils and T cells to respond at the site, capillary permeability is increased, creating inflammation and, thus, causing pneumonia to develop [8]. 

Risk Factors 

Several factors increase the likelihood of certain individuals developing pneumonia. Major risk factors include [10]. 

• Age, 2 years old or younger 

• Age, 65 years or older 

• Environmental conditions, like crowded areas or air pollution 

• Smoking 

• Drug and alcohol use, which weakens the immune system 

• Individuals who are immunocompromised, like people with HIV, AIDS, or bone marrow disorders 

• People with chronic respiratory conditions, like asthma, COPD, or cystic fibrosis 

Certain medical conditions, like diabetes, liver disease, and heart failure, also increase risk. Additionally, people with impaired swallowing ability or those who’ve had a stroke or head injury are also at a higher risk [10]. 

Etiology and Classification 

Pneumonia has three underlying causes or etiologies: bacteria, viruses, and fungi. The most common cause of pneumonia in adults in the U.S. is bacteria, with Streptococcus pneumoniae being the most common organism, followed by Staphylococcus aureus. Furthermore, different bacteria can cause usual or atypical presentations of pneumonia. For example, the bacteria Mycoplasma pneumonia causes an atypical presentation of pneumonia, also called “walking pneumonia” [8, 10]. 

Viruses can also contribute to developing pneumonia. In adults, influenza, parainfluenza, and rhinovirus are the top causes, while in children, respiratory syncytial virus (RSV) is the leading cause. The SARS-CoV-2 virus causes COVID-19 disease, which often contributes to developing COVID-19 pneumonia [8, 10]. 

Lastly, fungi and their spores can contribute to fungal pneumonia. In North America, Histoplasma, Coccidioides, and Blastomyces are common fungi causing pneumonia, while Aspergillus is the common cause of ventilator-associated pneumonia [8, 13]. For immunocompromised individuals, Pneumocystis jirovecii is a common fungal organism that causes pneumonia. Most healthcare providers refer to this type of pneumonia as PJP, formerly known as PCP pneumonia [10]. 

Many healthcare providers also classify pneumonia based on the clinical setting from which the initial source of infection was acquired. The three main types are ventilator-associated, community-associated, and hospital-acquired. Community-acquired pneumonia (CAP) is acquired from outside a hospital setting. If an individual develops pneumonia in their home or an outpatient facility, like assisted living or rehabilitation, it’s considered community-acquired [8]. 

Conversely, if a patient acquires pneumonia within a hospital setting 48 hours after admission, it’s considered hospital-acquired pneumonia (HAP). However, to be considered HAP, symptoms or incubation of pneumonia must not have been present during the time of admission. Lastly, ventilator-associated pneumonia (VAP) is like the name implies. VAP is pneumonia that develops 48 hours after endotracheal intubation [8].

Advanced Health Assessment 

History and Physical 

No matter the health setting where the diagnosis of pneumonia is made, the provider must complete a thorough history and physical assessment. Common signs and symptoms of pneumonia include: 

• Fever or chills 

• Lack of appetite or nausea 

• Myalgias 

• Fatigue or weakness 

• Cough, with or without sputum production 

• Shortness of breath [8]. 

Symptoms vary per patient, and some may have an atypical presentation. For example, fever, myalgias, and watery sputum are more correlated with viral pneumonia, while purulent or blood-tinged sputum may indicate bacterial etiology [8]. 

Conducting a thorough physical examination can aid in diagnosing pneumonia. Physical examination of patients with pneumonia often reveals tachycardia, tachypnea, and the presence of fever. Adventitious lung auscultation findings are typically present, like crackles, rales, or diminished breath sounds. Further lung evaluation may show consolation processes, such as decreased chest expansion, egophony, dullness to percussion, or increased tactile fremitus [8, 11]. 

Differential Diagnosis 

When conducting a history and physical, providers should also formulate potential differential diagnoses. Reviewing the patient’s medications, health history, comorbidities, and family and social history is useful when considering additional differentials. For example, if a patient has a history of deep vein thrombosis, is not taking an antithrombotic, and presents with a cough and shortness of breath, the provider should consider a pulmonary embolism as a differential. Formulating differentials is also based on possible etiologies.  

Differential diagnoses of bacterial pneumonia to consider include some of the following: 

• Asthma 

• Atelectasis 

• Bronchitis 

• COPD 

• Lung abscess 

• Respiratory failure  

[7,11] 

Differential diagnoses of bacterial pneumonia in children are different. The provider should consider diagnoses like asthma, croup, epiglottitis, or bronchiolitis in their differential [7,11]. For viral pneumonia, other differentials to potentially consider are pulmonary hypertension, pulmonary fibrosis, hyperreactive airway disease, and pulmonary edema [6]. For fungal pneumonia, possible differentials may be coal worker’s pneumoconiosis, neurogenic pulmonary edema, tuberculosis, and eosinophilic pneumonia [9]. While this list is not all-inclusive, it does provide valuable insight that providers should consider a vast array of possibilities when formulating possible differential diagnoses.  

Diagnostic Tests 

Diagnostics tests are useful to help make a diagnosis of pneumonia and can help reduce the likelihood of other health conditions. Initial tests are determined by the initial healthcare setting in which the patient is presenting and their acuity. Diagnostic tests to help make the diagnosis of pneumonia include [6,11]. 

• Chest X-ray: the appearance of pulmonary infiltrates or opacities helps support a pneumonia diagnosis. Specific lobes or interstitial infiltrates may indicate other disease processes, like heart failure or tuberculosis. 

• Complete Blood Count (CBC) with differentials: an elevated white blood cell count (WBC) shows signs of infection. Bacterial pneumonia is correlated more with an elevated WBC than with viral. 

• Complete Metabolic Panel (CMP): helps evaluate kidney function and assess for dehydration. Evaluating impaired kidney function is necessary when tailoring treatment plans. 

• Inflammatory biomarkers: An increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) indicates inflammation. However, these tests can be non-specific [6,11]. 

While typically, the diagnosis of pneumonia can be initially made by correlating clinical findings with radiological and laboratory results, it can still sometimes be challenging to determine the likely etiology, especially for those with an unclear history. Thus, additional diagnostic tests are considered in the appropriate setting.  

Additional tests may include [6,11]: 

• Blood cultures: can help determine the presence of bloodstream pathogens, which in turn helps determine the appropriate antibiotics for treating bacterial or fungal pneumonia. However, blood cultures must be collected before any treatment medications are administered. 

• Sputum analysis or culture: can also help determine possible etiology. These are especially helpful in an outpatient setting.  

• Rapid antigen tests: certain rapid antigen tests can help identify viral pathogens, like RSV, herpes simplex virus, influenza, or coronavirus. 

• Viral culture: if viral etiology is suspected, a viral culture may be necessary to identify the pathogen, especially when rapid antigen testing is not available for the specific virus.  

• Chest CT: sometimes pneumonia may not be clear on chest X-ray alone, or another differential is highly suspected. A chest CT provides greater detail of lung processes and should be completed when a pneumonia diagnosis is unclear [6,11]. 

Diagnostic Reasoning and Critical Thinking 

When considering the differential diagnoses of pneumonia, the healthcare provider should gather and analyze all of the pertinent data. The history of the present illness can provide valuable insight into the features of pneumonia and, most likely, its etiology. For example, if the patient reports a cough with blood-tinged sputum, myalgias, and a fever, bacterial etiology may be the most likely. However, if the patient lacks a fever and states they have a cough with blood-tinged sputum and shortness of breath, then a pulmonary embolism should also be added to the likely differential. On the other hand, patients with viral etiology, such as influenza, may have an initial sudden onset of symptoms like fever, myalgias, sore throat, fatigue, and nonproductive cough. Their symptoms may persist and develop into viral pneumonia over several days. 

Providers should also consider the patient’s risk factors and known exposures. For instance, if the patient has a history of HIV and develops a fever, cough, dyspnea, and lower lung field crackles, then fungal pneumonia (more specifically, PJP pneumonia) should be suspected. Since the patient is immunocompromised, other pneumonia etiologies are still considered, like mycoplasma, tuberculosis, COVID-19, etc. [14]. Another example is a college student who lives in crowded dorms and develops myalgias, fever, and a cough. They are at risk for certain etiologies and types of pneumonia, like tuberculosis, COVID-19, or “walking pneumonia.” 

Patient comorbidities should also be considered when determining the differential. For example, if they have a history of asthma and present with a cough and shortness of breath, then asthma should be considered as a lead possibility. Comorbidities, especially for those with CAP, also guide the treatment of pneumonia. For instance, a patient with a history of advanced COPD and a penicillin allergy will likely require fluoroquinolone. When compared to a healthy patient with no comorbidities or penicillin allergy, amoxicillin alone or plus a macrolide can be prescribed, depending on which current guidelines the provider follows [4]. 

The setting where the patient’s symptoms developed is also imperative when considering differentials. If a patient developed symptoms shortly after being intubated rather than at home, then the most likely etiologies will differ.  

Additionally, the setting determines initial diagnostic testing. If a patient is located in an outpatient facility without STAT lab capabilities, an initial diagnostic workup may include a chest X-ray and point-of-care testing. For atypical pneumonia presentation, a sputum culture may be helpful, but the provider should consider if the cough is productive. Alternatively, in an emergency department setting, diagnostic testing may include a chest X-ray, CBC, and CMP.  

Regardless of the setting, the provider should assess the patient’s overall condition and vital signs. If a patient’s oxygen saturation is 88% and temperature is 103°F in an outpatient facility, then immediately applying oxygen and transferring the patient to the hospital will be necessary. Once in the emergency department, the provider might consider ordering an arterial blood gas (ABG) and blood cultures along with the additional diagnostics mentioned above.  

Whether ordering diagnostic tests in an outpatient or inpatient setting, appropriateness and cost incurred to the patient should also be considered. For example, if an outpatient urgent care provider suspects a healthy patient has CAP, then a chest X-ray may be the only test required for diagnosis. If the provider suspects viral etiology, like COVID-19 or influenza, they may want to order viral point-of-care testing. However, tests and workups may vary depending on the health facility, as some facilities have specific testing protocols. 

Once a diagnosis of pneumonia is made, many healthcare providers also use the CURB-65 (confusion, uremia, respiratory rate, blood pressure, age greater than 65) scoring tool to guide the treatment setting. If the patient is confused, uremia symptoms are present or BUN is greater than 20 mg/dL, respiratory rate is greater than 30 breaths/minute, blood pressure is less than 90/60 mmHg, and they are older than 65, one point is given for each positive. For patients with a total score of one or less, they can likely be treated in an outpatient environment, 2 or more require hospitalization, and 3 or more intensive care admission [11]. 

The SMART-COP score is also useful in determining pneumonia severity in an emergency room or inpatient environment. It scores the patient’s systolic blood pressure, whether multi-lobar infiltrates are present, albumin levels, respiratory rate, presence of tachycardia, new-onset confusion, oxygenation status, and pH [11].

Pharmacological Treatment 

The treatment of pneumonia is determined by etiology and type and is further discussed below. Please note that these are general guidelines, and treatment plans should be tailored to each individual. As guidelines vary per medical organizational approach and are updated frequently, please refer to current practice guidelines. 

Bacterial Pneumonia 

For the treatment of CAP in a healthy individual who is less than 65 years old in an outpatient setting, amoxicillin monotherapy or amoxicillin plus a macrolide or doxycycline is used. If the patient is allergic to penicillin, a third-generation cephalosporin, like cefpodoxime, plus a macrolide or doxycycline can be prescribed. Or a macrolide or doxycycline alone can be used.  

For patients with significant comorbidities, advanced age, and other risk factors that are not penicillin-allergic, prescribing amoxicillin-clavulanate plus a macrolide or doxycycline is recommended. If they are allergic to penicillin, a third-generation cephalosporin plus macrolide or doxycycline is recommended. For patients unable to tolerate penicillin or cephalosporins and with structural lung disease, respiratory fluoroquinolone is recommended. Again, this is determined by the approach and guidelines the provider is following. The provider should also consider local bacterial resistance rates, if any [4]. 

Treatment widely differs for patients with CAP who require hospital admission. Those without suspicion of methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonas CAP may receive an intravenous (IV) beta-lactam antibiotic regimen or a fluoroquinolone alone. Patients with CAP and MRSA or pseudomonas risk factors may be started on an anti-MRSA medication (vancomycin or linezolid), aztreonam, and an aminoglycoside. Individuals presenting with symptoms of sepsis usually are started on an array of empiric IV antibiotics until the underlying organism is identified. Empiric antibiotic therapy regimens may vary depending on the healthcare facility and protocols [5]. 

Hospital-acquired or ventilator-associated cases of bacterial pneumonia are also treated with IV antibiotics. Initially, treatment is typically guided by hospital or healthcare facility-specific antibiograms. Once the sputum or blood cultures return, the antimicrobial selection is tailored to the specific bacterial organism causing the infection [12]. 

Viral Pneumonia 

Supportive care is typically the mainstay of treatment of viral pneumonia. Patients should be encouraged to maintain or increase their hydration through oral intake. If they are intubated or unable to tolerate oral intake, IV fluids should be administered. Rest is another factor to promote. If required, oxygen supplementation and mechanical ventilatory support in an inpatient setting may be necessary.  

Specific antiviral therapy is determined by the underlying viral etiology. Influenza is typically treated with oseltamivir or zanamivir, while RSV, parainfluenza, and adenovirus are treated with ribavirin. Herpes simplex virus and varicella-zoster virus cases of pneumonia are typically treated with acyclovir [6]. 

Fungal Pneumonia 

Cases of fungal pneumonia are usually treated initially with amphotericin B. However, other antifungals, like fluconazole and ketoconazole, may be administered. In many instances, fungal pneumonia develops as an opportunistic infection. Providers should consider risk factors, such as immunosuppression, chemotherapy, bone marrow transplant, steroid use, and infected catheters, as potential causes of infection [9]. 

For patients with PJP, treatment options are outlined as outpatient versus inpatient. The first-line outpatient oral antifungal treatment is trimethoprim-sulfamethoxazole (TMP-SMX). For patients with a sulfa allergy, atovaquone alone or trimethoprim plus dapsone can be prescribed as an alternative. More severe cases of PJP require hospitalization with IV antifungals, where again, intravenous TMP-SMX is preferred as initial treatment. Moderate to severe cases may require treatment with pentamidine or primaquine. Corticosteroids are also given in an inpatient setting, especially for patients with HIV [14]. 

Monitoring and Follow-up 

Pneumonia can lead to a variety of complications. Thus, healthcare providers must monitor the patient’s health status for signs of clinical decompensation or deterioration. Complications to consider may include lung abscess, atelectasis, empyema, sepsis, multisystem organ failure, and acute respiratory failure. Heart complications, such as heart failure and pericarditis, may also develop. Bacteremia and sepsis may also develop, and patient death is another to consider [8,11].  

Whether inpatient or outpatient, patients with pneumonia require follow-up. In an outpatient setting, providers should schedule a follow-up appointment within 24 to 48 hours of beginning treatment to assess the patient’s response. Vitals signs and overall patient condition are assessed. A repeat chest X-ray is not required for re-evaluation unless the patient’s condition does not seem to be improving.  

Referral to pulmonology should also be considered, especially for patients with chronic lung conditions or resolved symptoms. Sometimes, patients may require additional diagnostic tests or hospitalization if symptoms are not improving with oral treatment [4]. 

Follow-up and monitoring in an inpatient environment will differ. The patient’s overall condition, including vital signs and hemodynamic stability, will be monitored. Upon diagnosis, the provider should also consider if the patient needs to be placed on isolation precautions, like droplet, airborne, etc. Depending on the patient's overall health condition, consultation with pulmonology, infectious disease, and intensive care is necessary.  

Repeat chest X-rays and laboratory tests may be ordered daily as well to assess clinical response to therapy.  Once the patient’s pneumonia begins to resolve with treatment, they are weaned from supplemental oxygen, and vital signs stabilize; convert them to oral treatment (if possible). Patient discharge planning should also continue. Upon hospital discharge, the patient should follow up with their primary care provider and pulmonologist within one week. They may also need to follow up with an infectious disease specialist [5]. 

Patients are also educated on pneumonia prevention strategies, such as receiving COVID-19, influenza, and pneumococcal vaccinations and seeking immediate care when symptoms develop [8,11].  

Conclusion

Pneumonia can lead to serious health complications, especially if left untreated. Healthcare providers should recognize the signs and symptoms of pneumonia and understand the clinical features of each type. If there is clinical suspicion of pneumonia, additional diagnostics can help make the diagnosis. Additional testing may help rule up or down the likely etiology (bacterial versus viral versus fungal) and assess the patient’s overall acuity. Diagnostic reasoning and critical thinking are useful when creating a list of differentials and treatment options. Patient monitoring and follow-up are important aspects to consider as part of the patient’s treatment plan for both inpatient and outpatient environments. Education regarding prevention strategies is also helpful for future prevention.

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