Review of Medical Microbiology and Immunology, 13th Edition

76. Lower Respiratory Tract Infections

Contributed by Peter Chin-Hong, MD

CHAPTER CONTENTS

Introduction

Bronchitis

Bronchiolitis

Pneumonia

Lung Abscess

INTRODUCTION

Lower respiratory tract infections are an important cause of morbidity and mortality worldwide in children and in adults. Community-acquired pneumonia, for example, is the most deadly infectious disease in the United States. This chapter takes an anatomic approach to lower respiratory tract infections, moving from the large bronchi (bronchitis) down to the very small bronchioles (bronchiolitis) and then into the alveoli where pneumonia occurs.

BRONCHITIS

Definition

Bronchitis is a self-limited inflammation of the bronchi. Acute bronchitis must be distinguished from chronic bronchitis where patients have a cough for more than 3 months. The information in this chapter refers to acute bronchitis.

Pathophysiology

The coughing so characteristic of bronchitis is an attempt to clear the mucus produced by the inflammatory response to viral infection. Bronchitis occurs more often in the winter months than in the summer. Smoking predisposes to bronchitis (and pneumonia) by damaging the cilia in the bronchi, leading to an inability to clear mucus from the respiratory tract.

Clinical Manifestations

Cough is the most prominent symptom of bronchitis. Initially, bronchitis presents with the symptoms of an upper respiratory infection, namely, nasal congestion, scratchy sore throat, and perhaps a low-grade fever. Physical examination typically reveals expiratory wheezes. However, if cough persists for more than 5 days and pneumonia has been ruled out, acute bronchitis should be suspected. Bronchitis is self-limited and usually resolves in 1 to 2 weeks. However, cough may persist for several more weeks due to airway hyperreactivity.

Pathogens

Respiratory viruses are the most common pathogens (influenza A and B, parainfluenza virus, coronavirus, rhinovirus, respiratory syncytial virus [RSV], and human metapneumovirus). Bacterial pathogens are not thought to play a significant role in acute bronchitis.

Diagnosis

The diagnosis is primarily made clinically. Cough, with or without sputum production, which may persist for more than 5 days, is the typical presentation. Patients are usually afebrile but may have a low-grade fever. Sputum cultures are typically not done. In patients with chronic cardiorespiratory disease, a rapid antigen test for influenza virus may be useful because oseltamivir (Tamiflu) can shorten the duration and intensity of symptoms.

Because treatment of both upper respiratory infections and acute bronchitis is largely supportive, these distinctions may have less clinical significance. What may be more important clinically is to distinguish acute bronchitis (usually viral) from pneumonia (mainly bacterial; see section on Pneumonia), which does require antimicrobial therapy. A chest radiograph may be performed to determine whether pneumonia is present.

Treatment

Treatment involves reassurance and symptom relief with agents such as nonsteroidal anti-inflammatory drugs and/or a bronchodilator such as ipratropium. If influenza is diagnosed, oseltamivir (Tamiflu) may reduce the length and severity of symptoms. Antibiotics should be used only in those for whom a bacterial etiology has been clearly demonstrated.

Prevention

Influenza vaccine can prevent bronchitis and pneumonia caused by influenza A and B viruses. The neuraminidase inhibitor oseltamivir (Tamiflu) should be given to unimmunized individuals with chronic cardiorespiratory disease. Handwashing is recommended to reduce the carriage of respiratory viruses.

BRONCHIOLITIS

Definition

Bronchiolitis is inflammation of the bronchioles—the small airways less than 2 mm in diameter. The focus in this section will be on bronchiolitis among infants and young children where the etiology is primarily infectious.

Pathophysiology

Particularly among children under 2 years of age, viruses can directly damage the epithelial cells of the terminal bronchioles, causing inflammation and obstruction of the small airways. Prematurity is an important predisposing factor.

Clinical Manifestations

Usually children initially have symptoms consistent with an upper respiratory tract infection and then are noticed to have increased respiratory distress. Children under 2 years old in particular may have tachypnea, wheezing, nasal flaring, and chest retractions. In severe cases, hypoxia, apnea, and respiratory failure may ensue. In most cases, recovery occurs in 1 to 2 weeks.

Pathogens

RSV is the most common pathogen. Other etiologies include influenza virus, parainfluenza virus, adenovirus, coronavirus, rhinovirus, and human metapneumovirus. In children, viruses are the main etiology of bronchiolitis. Bacteria are not thought to be involved. In adults, the causes are more varied and range from viruses, to inhaled toxic chemicals in the workplace, to idiopathic causes. Bronchiolitis caused by RSV occurs primarily in the winter months.

Diagnosis

The diagnosis is primarily clinical. Upper respiratory tract infection symptoms followed by lower respiratory tract symptoms and signs (e.g., nasal flaring, wheezing) in a young child during the fall and winter would be very suggestive of bronchiolitis. Chest radiograph typically shows hyperinflation of the lungs. An enzyme immunoassay (EIA) for RSV antigen in respiratory secretions is available for diagnosis in hospitalized patients. A polymerase chain reaction (PCR) assay that detects the RNA of RSV is also available.

Treatment

Because this is a self-limited disease in most cases, general supportive measures are adequate in most cases. Patients with moderate or severe respiratory distress will require hospitalization. Ribavirin, delivered by aerosol into the lungs, is approved for severe disease caused by RSV, but its use is limited to hospitalized infants. Inhaled bronchodilators (albuterol or epinephrine) may be useful.

Prevention

Handwashing to minimize transmission of pathogens is an important strategy. Infection control procedures should be instituted in hospitalized patients to prevent the spread of viruses to others.

Palivizumab is a humanized monoclonal antibody against the RSV F (fusion) envelope protein that may be used in certain populations to decrease the risk of disease caused by RSV. These populations include children with bronchopulmonary dysplasia and congenital heart disease and prematurely born infants. An annual influenza vaccine in everyone older than 6 months of age is recommended. There is no viral vaccine against RSV.

PNEUMONIA

Definition

Pneumonia is an inflammation of the lung affecting the alveoli. We consider whether pneumonia is community acquired versus hospital acquired to help us determine the spectrum of potential pathogens that differs based on setting. More importantly, because empiric therapy is often given in pneumonia, therapeutic interventions differ based on the different populations. The focus in this section will be on community-acquired pneumonia. Hospital-acquired pneumonia, also known as nosocomial pneumonia, is pneumonia that occurs 48 hours or more after admission to the hospital and was not present at the time of admission.

Pathophysiology

The alveoli of the lungs are continually exposed to microbes from the environment via the upper respiratory tract. Our host defenses usually keep these potential pathogens in check. However, disease can occur when there is a particularly virulent organism, when there is a large burden of organisms inhaled from the environment or aspirated from the oropharynx, or when there is a defect in host immunity.

Predisposing factors to pneumonia include the extremes of age (the very young and very old), chronic obstructive pulmonary disease (COPD) and chronic bronchitis, diabetes mellitus, cystic fibrosis, and congestive heart failure. Injection drug users who overdose, alcoholics, and those with seizure disorders have a high risk of pneumonia because they can aspirate organisms into the lung when unconscious. People exposed to water aerosols, especially from air conditioners, are at risk for pneumonia caused by Legionella. Hospitalized patients in the intensive care unit are at risk for ventilator-associated pneumonia caused by gram-negative rods such as Escherichia coli, Pseudomonas, and Acinetobacter.

Clinical Manifestations

Symptoms include cough that may be productive of sputum, fever, chills, chest pain, and shortness of breath. “Rusty” sputum is a well-known finding in pneumococcal pneumonia. Sputum that has a “currant jelly” appearance occurs in pneumonia caused by Klebsiella because the organism is heavily encapsulated. Physical examination findings include tachypnea, rales, and rhonchi. If the lung is consolidated, dullness to percussion may be detected. Patients who are intubated and who acquire a nosocomial pneumonia may only have fever as a presenting sign, which may be accompanied by increased respiratory secretions or increased oxygen requirements. Pneumonia may be complicated by an infected pleural effusion or a pleural empyema. A pleural empyema is a walled-off collection of pus in the pleural space.

Pathogens

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Other common bacterial pathogens include Klebsiella pneumoniae and Haemophilus influenzae. Note that it is the nontypeable strains of H. influenzae rather than the type B strain that cause pneumonia in elderly patients with COPD. Mycoplasma pneumoniae, Legionella species, and Chlamydophila pneumoniae are other pathogens reported. Infection with Mycobacterium tuberculosis can also manifest as a pneumonia. Note that in approximately 30% of adults with community-acquired pneumonia, no pathogen, neither bacteria nor virus, is isolated.

Table 76–1 shows the important causes of community-acquired pneumonia as a function of age. Note that the causes of pneumonia in a neonate are those acquired during passage through the birth canal. The main cause of pneumonia in an infant, Chlamydia trachomatis, is also acquired during passage through the birth canal but is a less aggressive pathogen so its onset in delayed. Note that M. pneumoniae is the most common cause in young adults.

TABLE 76–1 Important Bacterial and Viral Causes of Community-Acquired Pneumonia by Age (Listed in Order of Frequency)

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Table 76–2 shows the typical causes of community-acquired pneumonia as a function of various predisposing factors. In certain patient populations, Pseudomonas aeruginosa and other gram-negative organisms and Staphylococcus aureus may be important pathogens causing pneumonia. For example, P. aeruginosa, Stenotrophomonas, and Burkholderia cause pneumonia in cystic fibrosis patients, and S. aureus is a well-recognized cause of pneumonia in patients with influenza. People exposed to certain animals have an increased risk of pneumonia; for example, those exposed to psittacine birds such as parrots are at risk for psittacosis caused by Chlamydophila psittaci, and those exposed to the placentas of pregnant sheep are at risk for Q fever caused by Coxiella burnetii. People exposed to the spores of the anthrax bacillus in sheep wool may get “woolsorter’s disease,” a pneumonia caused by Bacillus anthracis.

Table 76–2 Predisposing Factors Associated with Typical Pathogens Causing Community-Acquired Pneumonia

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Common pathogens for hospital-acquired pneumonia include gram-negative rods such as E. coli, K. pneumoniae, P. aeruginosa, Enterobacter species, Serratia marcescens, Acinetobacter species, and gram-positive cocci, especially S. aureus.

The most common viral cause of pneumonia is influenza virus. However, other viral pathogens such as RSV, parainfluenza virus, adenovirus, human metapneumovirus, and SARS coronavirus can also cause pneumonia. In patients with reduced cell-mediated immunity, herpesviruses, such as herpes simplex virus, varicella-zoster virus, and cytomegalovirus, can cause life-threatening pneumonia. In certain geographical areas, such as the rural southwestern part of the United States, outbreaks of pneumonia caused by hantavirus have occurred.

Fungi such as Coccidioides and Histoplasma also cause pneumonia. Pneumocystis jiroveci causes pneumonia, especially in patients with acquired immunodeficiency syndrome (AIDS) with low CD4 counts.

Diagnosis

The “gold standard” for a diagnosis of pneumonia is an infiltrate on a plain chest radiograph (Figure 76–1). Clinical data may help, but ultimately the chest radiograph is the most important diagnostic tool. Sputum analysis for Gram stain and culture and blood cultures may be helpful in the hospitalized patient but are only optional in an outpatient setting because therapy is largely empiric for community-acquired pneumonia. In pneumonia caused by one of the encapsulated pyogenic bacteria, such as S. pneumoniae, the white blood cell count is frequently elevated and the number of neutrophils is often increased.

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FIGURE 76–1 Lobar pneumonia caused by Streptococcus pneumoniae. Arrow points to area of consolidation in right lung. (Reproduced with permission from McKean SC et al. Principles and Practice of Hospital Medicine. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)

It is important that sputum (not saliva) be sent to the lab for Gram stain and culture. If the specimen contains many neutrophils and few epithelial cells, then the specimen is likely to be sputum and will be analyzed. If, however, the specimen contains many epithelial cells and few neutrophils, then the specimen is saliva and will be rejected by the lab.

Pneumonia caused by M. tuberculosis is diagnosed by acid-fast stain of sputum and culture on mycobacterial medium. A PCR assay done directly on sputum is available also. Pneumonia caused by Legionella pneumophila is often diagnosed by urinary antigen. PCR tests for various respiratory pathogens such as M. pneumoniae, influenza virus, and RSV are useful in special circumstances. The cold agglutinin test is no longer recommended for the diagnosis of pneumonia caused by Mycoplasma.

Treatment

Treatment for community-acquired pneumonia is largely empiric because microbiologic diagnostic strategies are generally insensitive. Outpatients are generally treated with a macrolide such as azithromycin, a tetracycline such as doxycycline, or a respiratory quinolone such as levofloxacin. Inpatients may be prescribed ceftriaxone plus a macrolide or respiratory quinolone monotherapy.

Patients with suspected hospital-acquired pneumonia may be given broader spectrum agents such as a carbapenem depending on the local epidemiology, given that many hospital-acquired infections are multidrug resistant. Prompt initiation of antibiotics is important because morbidity and mortality increase after a delay of more than 8 hours. Drainage of an empyema or infected pleural fluid should be performed.

Prevention

The influenza vaccine is effective in decreasing the likelihood of pneumonia. The pneumococcal polysaccharide (nonconjugate) vaccine available for older adults is important in decreasing bacteremia associated with pneumonia and mortality but not the likelihood of pneumonia itself. Because it is the nontypeable strains of H. influenzae, rather than the type B strain, that are the most common cause of pneumonia, the conjugate vaccine against type B is not an important source of protection. Smoking cessation and treatment of alcohol abuse may also decrease pneumonia risk.

LUNG ABSCESS

Definition

Lung abscess is a necrotic process within the lung parenchyma that frequently results in a cavity with an air-fluid level.

Pathophysiology

Patients may aspirate oropharyngeal bacteria into the lower airways and alveoli. This usually occurs when the patient is in the recumbent position and cannot clear secretions. For example, aspiration can occur when a person is unconscious from drug overdose, excess alcohol intake, or the anesthesia that accompanies surgery. Poor oral hygiene is a common predisposing factor. A pneumonitis may first occur, but this can progress to necrosis in a week or so. A lung abscess caused by S. aureus may infect the lung via the bloodstream from a distant site of infection such as right-sided endocarditis in an intravenous drug user.

Clinical Manifestations

Patients present with symptoms typical of pneumonia with fever and productive cough. The sputum is often foul smelling, indicating the presence of anaerobes. These symptoms may be indolent and progress over a period of weeks. Systemic symptoms such as night sweats, fatigue, and weight loss may also be present.

Pathogens

The most common organisms are anaerobes or mixed aerobes and anaerobes that are part of the oral flora. Anaerobes commonly involved include Peptostreptococcus species, Prevotella species, and Fusobacterium nucleatum. Aerobes include Streptococcus milleri and S. aureus. (Clinicians often use the term “aerobe” rather than facultative to describe bacteria that are not anaerobic.)

Diagnosis

A chest radiograph shows a pulmonary infiltrate with a cavity, often with an air-fluid level (Figure 76–2). An air-fluid level occurs when the abscess erodes a bronchus and some of the pus in the abscess is coughed up and replaced by air. Pleural fluid, if present, and blood cultures may provide microbiologic data, but anaerobes may be difficult to identify.

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FIGURE 76–2 Lung abscess. Arrow points to air-fluid interface within the abscess. (Reproduced with permission from McKean SC et al. Principles and Practice of Hospital Medicine. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)

Treatment

Clindamycin or ampicillin-sulbactam are typical treatment options. Duration of therapy is usually 4 to 6 weeks. Patients who do not respond to antibiotics will require surgical drainage.

Prevention

There is no vaccine against the organisms that cause lung abscess. Preventive measures include good dental hygiene and avoidance of unconsciousness caused by drug overdose and alcohol abuse.