Pulmonary Medicine

General Approach to the Patient with a Respiratory Infection

What every physician needs to know:

Pneumonia, which remains a remarkably common problem, generally describes an acute infection of the lung. Although the term "pneumonia" is often appended to descriptions of a chronic interstitial, non-infectious process (e.g., the Idiopathic interstitial pneumonias), this chapter refers only to acute infection.


Pneumonia has traditionally been categorized into community-acquired (CAP) and hospital-acquired (HAP) pneumonias, the latter of which are sometimes referred to as nosocomial pneumonias. In the ICU, a new pneumonia that evolves in a patient who has received at least 48 hours of mechanical ventilation is ventilator-associated pneumonia (VAP). The distinction between CAP and HAP evolved based on the observation that patients with HAP were infected with a set of pathogens distinct from those noted in CAP. CAP was thought to be caused predominantly by Streptococcus pneumonia, Haemophilus influenzae, Legionella sp., Mycoplasma sp., and so on. However, HAP was most often due to highly worrisome pathogens like Pseudomonas aeruginosa and methicillin-resistant Staphyloccous aureus (MRSA).

With the diffusion of healthcare delivery beyond the confines of the acute inpatient setting, patients may now present to the emergency department with infections that are due to bacteria generally considered to be limited to HAP, and this change in microbiology led to the creation of the concept of healthcare-associated pneumonia (HCAP). Patients with HCAP have a community-onset process, but they are at risk for a broader array of pathogens. Not all infectious pneumonia are caused solely by bacteria. Potential pathogens include bacteria but also viruses, mycobacteria, fungi, and parasites. These last few infecting agents may not be important except in immunosuppressed subjects.

Aspiration pneumonia describes bacterial infections of the lower respiratory tract that are acquired by aspiration of oropharyngeal or gastric contents in patients who are predisposed to aspiration because of altered mental status or oropharyngeal or esophageal dysfunction. By contrast, aspiration pneumonitis is a chemical pneumonitis that is due to introduction of acidic gastric contents into the lung. Aspiration pneumonitis can mimic infectious pneumonia but is not specifically due to an infectious agent.

Are you sure your patient has pneumonia? What should you expect to find?

Irrespective of the causative agent or subtype, pneumonia is associated with a constellation of manifestations. One set of findings the relates systemic signs and symptoms of infection, while other findings are more specific to the lung injury that ensues from the specific infection. Patients generally present with fever, an elevated white blood count, cough, and dyspnea. In elderly patients and the immunocompromised, fever may be absent and the WBC count may remain normal. Occasionally, the only objective evidence of infection is a shift toward immature forms of WBCs. In severe cases, hypothermia, rather than fever, arises.

Given the potential range in disease severity associated with pneumonia (irrespective of the type), some patients may seem only mildly ill while others rapidly progress to shock and acute respiratory failure. Reflecting the lungs' involvement, the patient often has an elevated respiratory rate and may also be hypoxemic. Sputum production is variable; some patients present with copious sputum production while others (mainly the elderly) may have only a non-productive cough. Rarely and depending on the pathogen, the patient may describe hemoptysis.

All patients require a complete and detailed history before being diagnosed, as the physical exam itself is often unhelpful, and reliance on just physical exam has been documented to lead to both over-diagnosis and under-diagnosis of pneumonia. Specific aspects of the history taking should elicit the duration of symptoms, their progression, occupation/environmental exposures, and the presence of risk factors for HCAP. A careful assessment of the patient's immune status (e.g., HIV disease, recent chemotherapy) is also needed.

To evaluate disease severity, physicians should review vital signs. Evidence of tachycardia, hypotension, and/or shock require urgent attention and must be addressed while assessing the patient. Hypoxemia or airway instability should be corrected immediately; some patients require mechanical ventilation.

In the end, the diagnosis of pneumonia is a clinical one. The physician must assemble and integrate the information and patient presentation along with results from objective testing to determine whether the patient has pneumonia. Each aspect of the diagnostic testing undertaken in pneumonia has limited sensitivity; in other words, the differential diagnosis for an elevation in the WBC count is huge, as is the differential for an abnormal chest film.

Decision aids that can help make the diagnosis more objective include the clinical pulmonary infection score (CPIS), which integrates various aspects of the clinical presentation and the objective testing into a score such that, the higher the score, the more likely the patient is to have infectious pneumonia, rather than some other process. However, the CPIS has limited utility, as it has not been evaluated outside of use in VAP. Even within the arena of VAP, the diagnostic value of the CPIS appears to be limited.

A recently developed assay to measure serum procalcitonin appears to identify subjects who are likely to have a bacterial infection, so it may be a useful guide for initiating antimicrobial treatment. However, this assay is not widely utilized in the United States at present.

Beware: there are other diseases that can mimic pneumonia.

Many disease processes other than pneumonia can cause the signs, symptoms, and radiographic findings that are often attributed to pneumonia. At present, there is no objective gold standard for the diagnosis of pneumonia, and it remains a clinical diagnosis. Specific patterns of signs and symptoms and/or CXR findings were once thought to implicate a particular pathogen, but this observation is certainly false: no one finding or combination of findings is pathognemonic for a particular pathogen, and clinicians should avoid utilizing such a deterministic approach to this disease.

The differential diagnosis for patients who present with an acute respiratory syndrome along with radiographic evidence of an infiltrate is broad. Whether the patient is being evaluated for HAP or CAP, other conditions include:

  • Aspiration pneumonitis/Inhalation injury

  • Congestive heart failure

  • Malignancy

  • Connective tissue diseases with pulmonary manifestation

  • Idiopathic interstitial pneumonia (e.g., UIP, NISP)

  • Trauma (pulmonary contusion)

  • Transfusion-related acute lung injury

  • Acute lung injury/acute respiratory distress syndrome

  • Drug reaction

  • Radiation pneumonitis

In most instances, the clinical scenario excludes many of these possibilities (e.g., no history of transfusion, no trauma). In some cases, several of these syndromes may co-exist with an acute pneumonia. For example, pneumonia often exacerbates heart failure.

How and/or why did the patient develop pneumonia?

Not applicable.

Which individuals are at greatest risk of developing pneumonia?

Not applicable

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Laboratory testing focuses on identifying the etiologic pathogen, which generally involves cultures of sputum, blood, and pleural fluid (if present). For patients who cannot produce sputum, inducing sputum with the help of respiratory therapy should be considered. Blood cultures are recommended for patients with HAP, VAP, and HCAP. In some cases, the blood culture may be the only way that the etiologic pathogen is identified. In CAP, the evidence supporting routine blood cultures is more limited; except for critically ill patients with CAP, blood cultures are more likely to grow a contaminant than a true pathogen.

In mechanically ventilated patients, clinicians should consider obtaining lower airway cultures rather than tracheal aspirates, as lower airway cultures are more reliable than tracheal aspirates and are less likely to be confounded by upper airway colonization. Examples of ways to obtain lower airway cultures include bronchoscopic and non-bronchoscopic techniques. Bronchoscopic approaches include traditional broncheal alveolar lavage (BAL) and bronchial brush. Mini-BAL and blind-brush are options for non-bronchoscopic alternatives. Both bronchoscopic and non-bronchoscopic means for obtaining culture material are considered equivalent for diagnostic purposes in the non-immunocompromised host.

Other tools for identifying the pathogen include urinary antigen testing and serum antibody studies. Urinary antigen tests are commercially available for Streptococcus pneumoniae and selected Legionella species. The urinary antigen tests have limited sensitivity and specificity since they are positive only in the presence of select serotypes/species. Measuring specific antibody titres and then re-evaluating the subject weeks later to determine the convalescent titre has no value outside of clinical research.

In immunosuppressed patients, special stains should be ordered to evaluate sputum and BAL specimens for the presence of Pneulymocystis jerovicci and selected fungi, but these tests are of little value in otherwise normal hosts. When mycobacterial disease is clinically suspected because of the clinical and epidemiologic scenario, acid fast stains and subsequent cultures are appropriate. Gene probing of sputum and lower airway material can also prove helpful in the proper setting.

What imaging studies will be helpful in making or excluding the diagnosis of pneumonia?

The presence of an infiltrate on a chest radiograph (CXR) is central to the diagnosis of pneumonia. Without evidence of direct parenchymal involvement, it is unlikely that an infectious pneumonia explains a patient's syndrome. However, standard CXR has limitations: Portable anteroposterior films without an accompanying lateral image may miss up to 20 percent of acute infiltrates. Similarly, even a posterio-anterior film with a lateral is less sensitive then a dedicated CT scan of the chest (especially in immunosuppressed subjects).

Approximately 10 percent of patients with pneumocystis pneumonia have normal chest films; the presence of the infiltrate is detected only on a CT scan. Similarly, in immunosuppressed subjects, the CT clearly is more sensitive than the CXR for the diagnosis of pneumonia, as the burden of organisms needed to lead to an infection may be lower than what is required in a more normal host.

Physicians should not simply jump to a CT scan, but this modality is appropriate if pneumonia is suspected and the standard CXR is normal. In addition, if there is a question about the pattern of infiltrates after reviewing a CXR or if there is a need to improve the evaluation of the mediastinum, a CT is appropriate. Selected aspects of an infiltrate may be better appreciated with the resolution of a CT. For example, a CT can confirm the presence of a cavity, which can substantially shift the differential diagnosis in terms of microbiology.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of pneumonia?


What diagnostic procedures will be helpful in making or excluding the diagnosis of pneumonia?

Bronchoscopy is often indicated when there is accompanying hemoptysis, an abnormality on imagining suggesting malignancy, nonresolving pneumonias, atypical clinical features and/or exposures, or an immunosuppressed patient. In patients who require mechanical ventilation, many clinicians perform bronchoscopy to obtain lower airway samples in suspected VAP.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of pneumonia?


If you decide the patient has pneumonia, how should the patient be managed?

Emergency management of the patient who has pneumonia includes establishing an airway if needed and maintaining adequate oxygenation and ventilation. For patients who are in shock from their pneumonia, rapid fluid resuscitation is crucial. Half of septic shock is thought to be due to infection in the lung. If there is concern about an accompanying empyema, it should be drained.

Because of data indicating that the timeliness and appropriateness of antibiotics improves outcomes in every form of pneumonia, clinicians should strive to ensure that the patient receives treatment promptly--ideally within six hours of symptom onset or presentation--with antibiotics that are active in vitro against the culprit pathogen. Because of the need to ensure in vitro activity, and given that one may not know culture results for several days, it is important to design emipric and protocolized regimens based on local susceptibility data for patients who present to the ED and for those who develop some form of HAP. Failure to administer initially appropriate antibiotic therapy can increased the risk of death up to four times.

In patients with CAP, it is crucial to utilize regimens against S. pneumoniae, the most common pathogen in this syndrome, as many strains of S. pneumoniae are penicillin- and/or macrolde-resistant. The clinical implications of this resistance are unclear at best. In the US, it remains common to treat "atypical" pathogens like Chlamydia pneumoniae and Mycoplasma species. The importance of these pathogens is difficult to establish, and in some countries treatment for these organisms is not considered routine. There are multiple guidelines that can aid in antibiotic decision making, including those from the American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) and the British Thoracic Society. Compliance with national guidelines with respect to antibiotic decision making has also been shown to improve outcomes.

For patients at risk for bacteria like P. aerugnosa, MRSA, and other multi-drug-resistant organisms, broader initial therapy is recommended. These pathogens are of particular concern in persons with HCAP, HAP, or VAP, and tin hose who are immunosuppressed. Combination antibiotic regimens are typically employed as part of the initial treatment regimen to ensure that at least one of the agents is active in vitro against what is eventually found to be the primary organism. It is important to narrow therapy when cultures return in order to limit the development of resistance and contain costs.

Selected patients may be at risk for pathogens like (but not limited to) cytomegalovirus, filamentous molds, and Pneumocystis. In these patients, empiric treatment is recommended pending cultures. Patients infected with human immunodeficiency virus should be given empiric Pneumocystis treatment (e.g., TMP-SMZ) along with traditional antibiotics. Corticosteroids should also be given for suspected Pneumocystis pneumonia if there is significant hypoxemia. The role of corticosteroids in other settings in which pneumonia is a concern is controversial; routine corticosteroid administration is not usually recommended for CAP, HCAP, or HAP.

On average, patients require three or four days to achieve clinical stability after initial antibiotic treatment for pneumonia. Patients who progress/fail to respond need a careful review of all cultures to ensure that a resistant organism has not been missed. There may also be an undrained empyema that requires drainage. If the patient has developed diarrhea, he or she may have developed antibiotic-associated colitis. In cases in which the presentation was confusing, the situation may become more clear as time goes on, and an alternate diagnosis, as pulmonary embolism or heart failure, may become evident.

Given the diagnostic limitations of the approach to pneumonia, it is important to re-evaluate the situation continually and to have a low threshold for questioning the original diagnosis. Repeat chest imaging is often part of the re-evaluation process; for example, infiltrates that resolve in a few days are not likely to have been due to infection, while hypoxemia out of proportion to the imaging may suggest an occult pulmonary embolism.

The recommended follow-up varies based on the type of pneumonia. For CAP, guidelines recommend a follow-up radiograph at six to eight weeks after onset in order to ensure that the infiltrate has resolved and that there is no confounding malignancy. For VAP, no specific follow-up is recommended.

What is the prognosis for patients managed in the recommended ways?

Prognosis is best determined based on traditional measures of outcome prediction. Specifically, the presence or absence of key organ failure (e.g., respiratory failure, shock) is a major determinant of outcome. For both CAP and HAP, scoring tools that measure the severity of illness perform moderately well at predicting outcomes, but they have certain limitations. For CAP, the CURB-65 scoring tool and the Pneumonia Severity Index correlate with mortality. For HAP and VAP there are no well validated scores uniquely developed to predict outcome.

For both HAP and CAP, most patients who will improve will do so by day three. In VAP, the Pa02/Fi02 ratio by day three is the best predictor of outcome. Multiple biomarkers correlate with outcomes, although these biomarkers tend to be non-specific.

What other considerations exist for patients with pneumonia?


What’s the evidence?

Niederman, MS, Mandell, LA, Anzueto, A, Bass, JB, Broughton, WA, Campbell, GD. "Guidelines for the management of adults with community acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy and prevention". Am JRespir Crit Care Med. vol. 163. 2001. pp. 1730-1754.

Important guidelines document issued by the American Thoracic Society.

Woodhead, M, Blasi, F, Ewig, S, Garau, J, Huchon, G, Leven, M. "Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections--summary". Clin Microbiol Infect. 2011. pp. 1-24.

A European guidelines document that provides up-to-date, evidence-based recommendations on management of pneumonia.
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