Pathophysiology

Pneumonia commonly results in ventilation-perfusion mismatch (with or without shunting) and hypoxemia.

Ventilation-perfusion inequality generally manifests as hypoxemia. Although shunt may explain part of the hypoxemia, ventilation-perfusion mismatch with areas of low ventilation-perfusion ratio is usually a more important factor. Carbon dioxide retention is not typically a feature of pneumonia unless the patient already has extremely limited reserve, especially from underlying COPD. In fact, otherwise healthy patients with pneumonia frequently hyperventilate and have a PCO2 less than 40 mm Hg, especially early in the course of the disease.

The systemic response to pneumonia is not unique but rather a reflection of the body’s response to serious infection. Perhaps the most apparent aspects of this response are fever, an outpouring of PMNs into the circulation (particularly with bacterial pneumonia), and often a “toxic” appearance of the patient. These indirect systemic responses can be clues that an infectious process is the cause of a new pulmonary infiltrate.

Clinical features and initial diagnosis

Most patients with pneumonia, especially younger and immunocompetent individuals, typically present with fever, cough, and often shortness of breath. The cough is nonproductive in some cases, particularly in pneumonias due to viruses or Mycoplasma; in others, especially bacterial pneumonias, sputum production is a prominent feature. When the inflammatory process in the pulmonary parenchyma extends out to the pleural surface, the patient often reports pleuritic chest pain. If the fever is high and “spiking,” patients frequently experience shaking chills associated with the rapid rise in body temperature. Importantly, older patients and those with chronic illness may not mount a robust immune response; thus, fever and cough may be lacking. Such patients may present with only nonrespiratory symptoms such as confusion, lethargy, poor oral intake, and an exacerbation of underlying disease (especially congestive heart failure or COPD).

Physical examination reflects the systemic response to infection and the ongoing inflammatory process in the lung. Patients often have tachycardia, tachypnea, and fever. Examination of the chest typically reveals inspiratory crackles overlying the region of the pneumonia. If dense consolidation is present and the bronchus supplying the area is patent, sound transmission is greatly increased through the consolidated pneumonic area. As a result, breath sounds may be increased and bronchial in quality, fremitus is increased, and egophony is present. The consolidated area is characteristically dull to percussion of the overlying chest wall (see Chapter 3). Examination of peripheral blood typically shows an increase in white blood cell count (leukocytosis). Especially in patients with bacterial pneumonia, the leukocytosis is composed primarily of PMNs, and a shift toward greater numbers of immature neutrophils such as band forms may be seen.

Frequent clinical features in patients with pneumonia:

1.Fever (with or without chills)

2.Cough (with or without sputum)

3.Dyspnea

4.Pleuritic chest pain

5.Crackles overlying affected region

6.Dullness, bronchial breath sounds, and egophony with frank consolidation

7.Polymorphonuclear leukocytosis

Therapeutic approach: General principles and antibiotic susceptibility

The cornerstone of treatment of bacterial pneumonia is prompt and effective antibiotic therapy directed at the infecting organism. However, the causative organism is identified in less than 40% of cases, even after extensive testing, Therefore, initial treatment strategies have been developed on the basis of the clinical setting (i.e., community-acquired vs. nosocomial pneumonia). The specifics of the treatment strategies are outlined later under “Initial Management Strategies Based on Clinical Setting of Pneumonia.” These guidelines were developed by expert consensus through consideration of the most likely organisms to be involved, the principles of antibiotic stewardship, and to some extent, the risk of delayed treatment. The concept of antibiotic stewardship has grown from the recognition that overuse of antibiotics leads to marked increases in antibiotic resistance. The goal is to use the most narrow spectrum antibiotic regimen possible to treat an infection in an effort to limit the development of resistant organisms.

As the risk of infection by any of multiple different organisms becomes greater, the spectrum of the recommended antibiotic regimen(s) increases. Implicit in these guidelines is an understanding of the risk of delayed treatment. In addition, there will be some patients with an infection for whom the guidelines recommend initial treatment that will not be effective. This potential risk reinforces the need to carefully assess each patient for risk factors for unusual organisms. The guidelines attempt to balance these three goals: treating the most likely organism, using the most narrow spectrum antibiotic regimen, and minimizing the risk of starting treatment that is ineffective. Thus, the recommended antibiotic regimens escalate from a very narrow treatment focused primarily on S. pneumoniae (amoxicillin) in younger healthy individuals, to a broad-spectrum regimen that is unlikely to miss any bacteria in patients who are severely ill. Table 23.1 summarizes the etiology of four broad subcategories of patients with communityacquired pneumonia. If and when an organism is identified, the regimen is narrowed to allow for more focused or more effective antibiotic coverage. Because knowledge of antibiotic susceptibility of specific organisms helps with understanding the rationale behind initial treatment strategies, this section will consider some of the general patterns of antibiotic susceptibility for the major organisms causing pneumonia.

TABLE 23.1

Community-Acquired Pneumonia: Common Organismsa

aExcludes patients with human immunodeficiency virus infection.

C. pneumoniae, Chlamydophila pneumoniae; H. influenzae, Haemophilus influenzae; M. catarrhalis, Moraxella catarrhalis; M. pneumoniae, Mycoplasma pneumoniae; M. tuberculosis, Mycobacterium tuberculosis; S. aureus, Staphylococcus aureus; S. pneumoniae, Streptococcus pneumoniae.

Modified from Mandell, L. A., Wunderink, R. G., Anzueto, A., Bartlett, J. G., Campbell, G. D., Dean, N. C., et al. (2007). Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clinical Infectious Diseases, 44 (Suppl. 2), S27–S72.

Before moving on, however, we will define two confusing terms: typical pneumonia and atypical pneumonia. These are historical terms that actually do not provide a clear distinction and in general should be avoided. However, the terms are so embedded in the literature that we will define them here. The origin of these terms is likely based on the historical recognition of mycoplasma pneumonia (i.e., due to Mycoplasma pneumoniae). Streptococcus pneumoniae was the first organism recognized to cause an acute pneumonia (i.e., pneumococcal pneumonia) and for many years was the only known cause. Pneumococcal pneumonia classically presents with a high fever, lobar infiltrate, a Gram stain of sputum revealing organisms consistent with the diagnosis, and response to penicillin or other β-lactam

antibiotics. Soon after radiographs were more commonly used, it was recognized that some patients with

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symptoms of pneumonia had chest x-rays that showed patchy, scattered infiltrates, were not as ill, had no organisms seen on Gram stain of sputum, and did not respond to penicillin. In retrospect, it is likely that many of these cases were due to M. pneumoniae. This “new” pattern was labeled “atypical pneumonia,” and pneumococcal pneumonia was considered “typical pneumonia.” Thus, “atypical pneumonia” has come to mean pneumonia caused by bacterial organisms that cannot be seen on Gram stain or cultured by standard techniques and are intrinsically resistant to β-lactam antibiotics. Mycoplasma, Chlamydophila, and Legionella are included in this category. “Typical pneumonia” includes other common respiratory bacterial pathogens, most notably S. pneumoniae (the most common bacterial cause), Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and other aerobic Gram-negative rods.

Because S. pneumoniae is the most common cause of bacterial pneumonia, initial treatment for all patients should cover this organism. Penicillin has traditionally been the most appropriate agent, assuming the patient is not allergic to it, and amoxicillin (an oral penicillin derivative) is recommended for uncomplicated pneumonia in otherwise healthy patients. However, amoxicillin is not effective against some of the other common causes of community-acquired pneumonia (e.g., M. pneumoniae, Chlamydophila pneumoniae). Previously, macrolide antibiotics were recommended as a single agent for empiric outpatient therapy in uncomplicated pneumonia, but the prevalence of macrolide-resistant S. pneumoniae has caused a change in this recommendation.

Staphylococci generally produce penicillinase, which requires the use of a penicillinase-resistant semisynthetic derivative of penicillin, such as oxacillin or nafcillin, or a first-generation cephalosporin such as cefazolin. Unfortunately, many staphylococci (methicillin-resistant S. aureus, or MRSA) are also resistant to these agents, in which case vancomycin is the antibiotic of choice. H. influenzae may be sensitive to ampicillin, but the high frequency of organisms resistant to this antibiotic generally justifies alternative coverage, such as a secondor third-generation cephalosporin, an extended-spectrum macrolide, trimethoprim-sulfamethoxazole, a quinolone, or a β-lactam/β-lactamase inhibitor combination. Many of the other Gram-negative bacillary pneumonias often display resistance to a variety of antibiotics. Aminoglycosides (e.g., gentamicin and tobramycin), thirdor fourth-generation cephalosporins, quinolones, carbapenems (e.g., meropenem), or an extended-spectrum penicillin with a β-lactamase inhibitor (e.g., piperacillin/tazobactam) may be used initially while antibiotic sensitivity testing is performed. Pneumonia caused by anaerobes is treated most commonly with either penicillin or clindamycin. A macrolide or a quinolone is the antibiotic of choice for pneumonias caused by either

Legionella or Mycoplasma.

Frequently used targeted antibiotics for common organisms causing pneumonia:

1.S. pneumoniae (penicillin or ampicillin, firstor second-generation cephalosporin, selected quinolones, macrolide in areas where resistance is low)

2.Staphylococcus (oxacillin, nafcillin, cefazolin, vancomycin)

3.Haemophilus influenzae (secondor third-generation cephalosporins, trimethoprimsulfamethoxazole, quinolone, macrolide)

4.Gram-negative rods (aminoglycosides, thirdor fourth-generation cephalosporins, carbapenems, extended-spectrum penicillin with β-lactamase inhibitor)

5.Anaerobes (penicillin, clindamycin)

6.Mycoplasma organisms (macrolide, quinolone)

7.Legionella (macrolide, quinolone)

8.Chlamydophila pneumoniae (tetracycline, macrolide)