on 25-Jan-2024 (Thu)

In 1901, Sir William Osler noted in the fourth edition of his book The Principles and Practice of Medicine that “the most widespread and fatal of all acute diseases, pneumonia, is now Captain of the Men of Death.”1

Because a specific etiologic diagnosis is often not pos- sible at the time initial treatment is begun, the clinician must decide which empirical therapy is most appropriate.

The history should attempt to define (1) symptoms consistent with the diagnosis of pneumonia or not, (2) the clinical setting in which the pneumonia takes place, (3) defects in host defense that could predispose to the development of pneumonia, and (4) possible exposures to specific pathogens

In addition, nonrespiratory symptoms are commonly present including fatigue, sweats, headache, nausea, and myalgia, and occasionally abdominal pain and diarrhea.60

The clinician should ask the patient about symptoms that are often associated with pneumonia including cough, sputum production, dyspnea, chest pain, and fever.59 They should also ask if patient has hemoptysis, hoarseness, vomiting, or trouble swallowing and should inquire about recent travel, weight change, and smoking.

With increasing age, both respiratory and nonrespira- tory symptoms of pneumonia become less frequent.

Unfortunately, symptoms at presentation elucidated by a careful history may not always aid in distinguishing pneumonia from other respiratory problems.

Pneumonia due to M. pneumoniae occurs more often in younger people, but in older patients it may be a cause of pneumonia severe enough to necessitate hospitalization.62

Gram-negative bacterial pneumonia tends to occur in older adults, especially those who are debilitated with comorbid diseases or are ill enough to require intensive care unit (ICU) care

Tuberculosis should be suspected in persons who have lived in countries where tuberculosis is endemic, are homeless, are infected with HIV, have a history of latent tuberculosis, or have been exposed to others with the disease

Staphylococcal pneumonia classically has been noted during epidemics of influenza,63 yet was shown to cause only 1.6% in a study of over 2000 adults in the United States with CAP, with only 0.7% of the total cohort being due to methicillin-resistant Staphylococcus aureus (MRSA).64 Despite this fact, the study noted that 30% of the adults received antibacterials targeting MRSA

Pneumonia has been noted to occur with increased frequency in patients with a variety of underlying disorders such as congestive heart failure, diabetes, alcoholism, and COPD. In one series of 292 patients with pneumonia, only 18% were found to have no underlying disease.65

Certain lifestyle factors have also been associated with an increased risk of pneumonia. These include cigarette smoking, alcohol use (especially in males), contact with children and pets, and living in a household with more than 10 people.66

Viral upper respiratory tract infections can predispose to pneumonia, and may be associated with more severe disease.67,68

Recent dental manipulations, sedative overdoses, seizures, alcoholism, or loss of consciousness for any reason should raise the suspicion of anaerobic infection caused by aspiration of oral contents.26

Special note needs to be made of the relationship between pneumonia and patients with COPD.69 Although well-controlled studies are lacking, it does appear that patients with COPD have an increased incidence of pneumonia. However, because the tracheobronchial tree is often colonized with Streptococcus pneumoniae and H. influenzae, it has been difficult to distinguish clearly between colonization and infection in many studies

Patients with CF more often have pneumonia due to Pseudomonas and staphylococci,57 and Burkholderia spp., Stenotrophomonas spp., Achromobacter xylosoxidans, and atypical mycobacteria.

Pulmonary alveolar proteinosis can be associated with Nocardia infection

In considering the etiology of pulmonary infection in patients infected with HIV, providers should consider geographic exposures, demographic characteristics of the patient, and the degree of immune suppression.

Bacterial pneumonia was a significant complication for HIV-infected individuals in the preantiretroviral era, with an incidence 5- to 10-fold that seen in the general population, and the incidence of invasive pneumococcal disease was more than 50-fold higher in in HIV-infected patients than in non–HIV-infected controls.76,78

Although relatively less common in the developed world, in developing countries, Mycobacterium tuberculosis is now viewed as the major pulmonary pathogen in patients with AIDS.74

In the severely immunosuppressed HIV population, fungal infections can play a major role, and depending on the patient’s exposure history, cryptococcosis, histoplasmosis, blas- tomycosis, and coccidioidomycosis should be considered

Pneumocystis and disseminated tuberculosis are associated with CD4 counts below 200/mm3, and disseminated nontuberculous mycobacterial and fungal infections occur with CD4 counts less than 50 to 100/mm3.80

Pneumonia developing in hospitalized patients may involve Entero- bacteriaceae, P. aeruginosa, and S. aureus, organisms that are unusual in community-acquired disease.81

Pneumonia is a manifestation of aging: the annual incidence of pneumonia necessitating hospital admission rises with age, and those aged 80 years or older have the highest rate (164 per 10,000 adults).84

Important aspects of a patient’s history that may suggest specific potential infectious agents include occupational, animal, and travel history (Table 67.3).

A carefully obtained history may also suggest the presence of noninfectious pulmonary disease, such as tumors, sarcoidosis, granulomatosis with polyangiitis (GPA; previously known as Wegener granulomatosis), or pulmonary emboli, all of which may masquerade as pneumonia.

Patients with a history of several episodes of “pneumonia” with abnormal imaging that does not resolve need to be evaluated for a noninfectious cause

Most, but not all patients with acute pneumonia appear ill, although the elderly can appear apathetic.

Fever is reported to be present in 65% to 90% of patients with pneumonia. It may be sustained, remittent, or at times hectic. Fever patterns per se, however, are not useful for

Oral temperature assessment should be avoided to reduce error caused by rapid mouth breathing

The pulse usually increases by 10 beats per minute for every degree (centigrade) of temperature elevation. A pulse-temperature deficit (e.g., a relative bradycardia for the amount of fever) should suggest viral infection, mycoplasmal infec- tion, chlamydial infection, tularemia, or infection with Legionella

Cyanosis, a rapid respiratory rate, the use of accessory muscles of respira- tion, sternal retraction, and nasal flaring suggest serious respiratory compromise

Bullous myringitis is an infrequent but significant finding in mycoplasmal pneumonia (was seen in volunteers given intranasal infections).

The presence of poor dentition should suggest a mixed infection due to aspiration of anaerobes and aerobes that colonize the oropharynx. Although edentulous patients may develop anaerobic pneumonia as a result of aspiration, it is uncommon.88

Examination of the thorax may reveal “splinting,” or an inspiratory lag on the side of the lesion, that is suggestive of bacterial pneumonia

Deep breathing can provoke cough.

Early in the disease process, definitive signs of pulmonary involvement may be lacking or may manifest only as fine rales

Evidence of consolidation (dullness on percussion, bronchial breath sounds, and egophony [E to A changes]) is highly suggestive of bacterial infection but may be absent in two-thirds of patients ill enough to be hospitalized and may be absent more often in patients treated as outpatients.89

Patients with Mycoplasma, Pneu- mocystis, tuberculosis, or viral infection may exhibit few abnormalities at physical examination despite the presence of impressive infiltrates on chest images

However, a great deal of interobserver variation has been shown to exist. In one series, three examiners seeing the same patients could not consistently agree on the physical examination findings. The diagnosis of pneumonia could be made with a sensitivity of only 47% to 69% and with a specificity of 50% to 75%.90

Rare findings such as egophony and asymmetrical chest movements have a high predictive value for pneumonia, but occur so infrequently that they are of limited usefulness.

The combined use of the standard microbiologic testing in conjunction with nucleic amplification assays can define the cause of CAP in up to 89% of cases as compared with only 39% with culture.93

Pleural effusion or parapneumonic effusion will occur in 20% to 40% of hospitalized patients with pneumonia, and the incidence of severe pleural involvement has been increasing in recent years.144–146

The incidence of pleural effusions associated with pneumonia varies with the etiologic agent, from approximately 40% to 57% with pneu- mococci, to 50% to 70% with gram-negative bacilli, and up to 95% with β-hemolytic streptococci.103,147

Pleural fluid cultures, when positive, are specific for the organism causing the underlying pneumonia.

Thus, pleural fluid analysis should be strongly considered in patients with apparent pneumonia and pleural effusion when the radiologic findings are not consistent with fluid overload

If neutrophils are not the predominant cell type seen in the pleural space, a diagnosis other than bacterial pneumonia should be sought.

Parapneumonic effusions can be divided into three stages.144,147

The first stage, or exudative stage, is culture negative, has a pH of greater than 7.2, glucose greater than 60 mg/dL, and a lactate dehydrogenase (LDH) level that is less than three times the upper limit of normal. This stage is due to pulmonary interstitial fluid entering the pleural space and increased permeability of the capillaries in the pleura. These uncomplicated pleural effusions usually resolve with therapy for the underlying disease

Without appropriate therapy, pleural effusions become infected with the organisms causing the underlying pneumonia and develop into the second stage or fibropurulent stage. This stage is associated with positive microbial cultures, pH less that 7.2, glucose less than 60 mg/dL, and LDH that is greater than three times the upper limit of normal. Such complicated pleural effusions require drainage

The most sensitive finding in determining whether a pleural effusion needs drainage is a pleural fluid pH less than 7.2. This usually occurs before the other chemical parameters associated with complicated pleural effusions develop.144 If pH is used to determine if an effusion is to be drained, it must be measured with a blood gas machine, not a pH meter or pH indicator strip, which can be inaccurate.

Empyema is defined as pus in the pleural space and represents a late manifestation of complicated pleural effusions. The presence of empyema mandates draining the pleural space. Complicated pleural effusions can have a positive culture result in up to 24% of cases, making thoracentesis and culture of fluid a valuable means of making an etiologic diagnosis of the underlying pneumonia.148,149

Adenosine deaminase, an enzyme associated with lymphocytes, may also be used to detect M. tuberculosis, with reported sensitivity and specificity of over 90%,151,152 but actual performance in the field appears to be lower.

Blood cultures are positive in 4% to 17% of patients hospitalized with CAP, with the frequency of positive results increasing with the severity of illness.93,123,153–155

Some studies have suggested that positive blood cultures add little to the management of patients hospitalized with CAP and are not predictive of increased mortality.156–158 However, the presence of true positive blood cultures is highly specific, may be helpful in narrowing antibiotic use, and may identify the presence of unusual organisms that would not be adequately covered with routine empirical antibiotic coverage.159,160

Work has shown that several clinical features can be used to predict patients with a higher likelihood of having bacteremia.154,155 In particular, patients who have two or more of the findings of chronic liver disease, pleuritic pain, tachycardia, tachypnea, or systolic hypotension and the absence of prior antibiotic therapy have at least a 14% incidence of bacteremia, with a bacteremia incidence of up to 63% in those with four or more of these findings.155

It is clear that blood cultures should be obtained before antibiotic administration in all patients with CAP who are ill enough to be hospitalized who have two or more of these features, and in those patients who are immuno- compromised, who have been admitted with health care–associated pneumonia (HCAP), or who acquire pneumonia in the hospital.

The IDSA and ATS have also recommended blood cultures for patients who are admitted to an ICU and have a cavitary lesion, leukopenia, active alcohol abuse, asplenia, a positive pneumococcal urinary antigen, or a pleural effusion.95 Furthermore, because the cause of pneumonia is not always found, assessment of clinical response to initial therapy is important, and blood cultures should be obtained in patients not responding to antibiotic therapy.160

Soluble L. pneumophila antigen can be detected in urine using a com- mercially available EIA. Although it is useful only for detecting L. pneumophila serogroup 1, this assay offers the advantage of being rapid and noninvasive and has a sensitivity of 80% to 95% and a specificity estimated to be 99% for this serogroup.112 An additional relative limitation of this assay is that antigenuria may persist for weeks to months after therapy

An immunochromatographic membrane test has been developed to detect the C polysaccharide cell wall antigen found in all S. pneumoniae in urine of patients with pneumonia (Binax NOW).187 This has been reported to be an extremely useful means of diagnosing pneumococcal pneumonia. With use of a variety of standard diagnostic tests as controls, overall sensitivities of 65.5% to 100%, specificities of approximately 94% to 100%, and positive predictive values of 62% have been noted.188–190

Potential problems with the urinary antigen assay include weakly positive results caused by non- pneumococcal organisms, false-positive results in children with nasopharyngeal carriage rather than true infection, and positive results lasting for weeks after the infection has resolved.161,189

In addition, retrospective analysis has not found an impact of the routine use of the test on antibiotic prescribing practices for patients with suspected pneumonia, although in hospitalized patients it may allow deescalation of antibiotics.191

Chest radiography plays a critical role in the diagnosis of pneumonia, and it represents the gold standard of making a clinical diagnosis.

Dem- onstration of an abnormal chest radiograph with pulmonary infiltrates consistent with pneumonia differentiates a patient population that may benefit from antibiotic therapy from the populations that will not.

The extent and nature of radiographic abnormalities may define patients who are more seriously ill and may need close monitoring.

The infiltrate patterns found on chest radiographs in patients with pneumonia usually are not helpful in making a specific etiologic diagnosis (Fig. 67.8A–B).193 However, certain features may be of some diagnostic aid (Table 67.4).

Lobar consolidation, cavitation, and large pleural effusions support a bacterial cause (Figs. 67.9 and 67.10).

Most lobar pneumonias are pneumococcal, although pneumococcal pneumonias are not necessarily lobar.

When bilateral diffuse involvement is noted, Pneumocystis pneumonia, Legionella pneumonia, or a primary viral pneumonia should be suspected

Staphylococcal pneumonia may result from infection metastasizing from a primary focus unrelated to the lung. In these cases, multiple nodular infiltrates throughout the lung may be seen

Staphylococci may cause marked necrosis of lung tissue with ill-defined thin-walled cavities (pneumatoceles), bronchopleural fistulas, and empyema, especially in children (Fig. 67.11). S. aureus producing the Panton-Valentine leukocidin, whether methicillin resistant or not, is associated with necrotizing pneumonia with multilobar cavitary lesions and is frequently associated with pleural effusions and empyema.194,195

Although pneumatoceles are diagnostically significant findings in staphylococcal pneumonia, they may be seen in pneumonias with other causes, including K. pneumoniae, H. influenzae, S. pneumoniae, and, more rarely, Pneumocystis.

Pulmonary infections due to Pseudomonas may cavitate. Pseudomonas and other gram-negative bacilli most com- monly cause lower lobe pneumonia

Aspiration pneumonia should be considered along with gram-negative and staphylococcal pneumonias as a source of necrotizing pneumonia, cavitation, and empyema.

Aspiration pneumonia commonly involves either the superior segment or the basilar segment of either lower lobe, or the posterior segment of the upper lobes, depending on whether aspiration occurred in the dependent or the upright position.

Chronic aspiration most commonly results in bilateral lower lobe pneumonia, although it may involve one side more than the other.

Viral infection of the lower airway involves respiratory epithelium and parenchyma adjacent to terminal respiratory bronchioles. Diffuse hemorrhagic congestion of alveolar septa may occur.196 The radiographic concomitants of these pathologic findings usually involve patchy areas of peribronchial ground-glass opacity, air-space consolidation, and poorly defined small nodules. Diffuse and localized involvement with both interstitial and alveolar patterns has been noted (Fig. 67.12).196

There is little radiologic distinction among the various viral causes of pneumonia.

Influenza pneumonia is associated with poorly defined, patchy air-space consolidation with rapid confluence. Varicella pneumonia usually involves peribronchial involvement with nodular infiltrates

Lobar or subsegmental consolidation mimicking bacterial pneumonia may also be seen with adenovirus and herpes simplex

Hantavirus pneumonia usually manifests with interstitial edema, which may progress to consolidation representing a pulmonary capillary leak syndrome.

Most cases of human metapneumovirus involve upper respiratory tract infections in children; pneumonia in adults has been described.201,202 Multilobar infiltrates have been noted in 50% of cases, and pleural effusions are not uncommon.

Mycoplasmal pneumonia often manifests with an interstitial pattern in a peribronchial and perivascular distribution.204 Consolidation is noted in approximately 38% of patients, usually in the lower lobe. Once this consolidation stage is reached, radiologic differentiation between bacterial and mycoplasmal pneumonia is difficult. Cavitation is rare, although pleural effusions may be seen in approximately 20% of cases.204,205

Chlamydia pneumoniae predominantly causes unilobar disease with associated air bronchograms.193

Legionnaires’ disease may initially manifest with a radiographic picture similar to that of mycoplasmal pneumonia. A patchy interstitial or finely nodular pattern is seen in the lower lobe.206 However, unlike the situation with mycoplasmal pneumonia, pneumonia with more than two-lobe involvement is commonly seen. Rapid progression and pleural effusions are also common. Pneumonia caused by Legionella micdadei may manifest with pulmonary nodules, either single or multiple, and with segmental infiltrates. As in pneumonia caused by L. pneumophila, rapid radiologic progression of the disease is characteristic.207

In the immunocompetent host, chest CT may reveal infiltrates not present on chest radiograph at the time of initial presentation to an emergency room and may rule out CAP in some patients.211

CT scans are also more sensitive in defining parenchymal disease in the ICU setting and in patients older than 65 years.

Certain infections, such as those caused by Aspergillus, M. tuberculosis, and Pneumocystis, have characteristic appearances on CT that in the correct clinical setting may make invasive procedures unnecessary.