Chapter 21. Lower Respiratory Tract Infections

Respiratory tract infections are a major cause of morbidity and mortality in the United States and represent a common reason for which patients seek medical care. The most common infections involving the lower respiratory tract are bronchitis, bronchiolitis, and pneumonia. Lower respiratory tract infections (LRTIs) in children and adults commonly result from viral or bacterial invasion of lung parenchyma. Viral infections are diagnosed by the recognition of characteristic constellation of clinical signs and symptoms. Treatment of viral LRTI consists largely of supportive care measures. Bacterial LRTIs (in particular bacterial pneumonia) requires expedient, effective, and specific antimicrobial therapy. An appropriate treatment regimen for the patient with a LRTI can be established with the aid of a thorough medical history, physical examination, chest radiograph, knowledge of common bacterial pathogens, and results of properly collected cultures. This chapter will focus on pneumonia; see the special considerations section of this chapter for information on bronchitis and bronchiolitis.

Pneumonia

Pneumonia is inflammation of the lung with consolidation and is the most common infectious cause of death in the United States.1 Approximately three million cases are diagnosed annually at a cost of more than $20 billion to the health care system. Pneumonia occurs throughout the year and in persons of all ages; however the most severe pneumonia cases are in the very young, the elderly, and the chronically ill. The main classifications of pneumonia are: community-acquired, hospital-acquired (including aspiration), and health care-associated (the term health care-associated pneumonia, as used in this chapter, includes hospital-acquired pneumonia [HAP], ventilator-associated pneumonia [VAP] and other health care-associated pneumonia [HCAP]).

The etiology of bacterial pneumonia varies in accordance with the type of pneumonia. Table 21-1 lists common bacterial pathogens associated with the various classifications of pneumonia.2-4 Viruses are a common cause of community-acquired pneumonia in adults (often coinfecting with bacteria), and in children (65%). Viral pneumonia in children is frequently caused by respiratory syncytial, influenza or parainfluenza virus.

Pathophysiology

Microorganisms gain access to the lower respiratory tract by three routes.5 Organisms may enter the lung via:

1. Inhalation of aerosolized particles.

2. The bloodstream from an extrapulmonary site of infection.

3. Aspiration of oropharyngeal secretions. Microaspiration is the major mechanism by which pulmonary pathogens gain access to the normally sterile lungs.

When pulmonary defense mechanisms are functioning optimally, aspirated microorganisms are cleared from the region before infection can become established. Local host defenses of the upper and lower respiratory tract and anatomy of the airway are important in preventing pneumonia. Upper respiratory tract defenses include: mucociliary apparatus of the nasopharynx, nasal hair, normal bacterial flora, IgA antibodies, and complement. Lower respiratory tract defenses include: cough, mucociliary apparatus of the trachea and bronchi, antibodies (IgA, IgM, and IgG), complement, and alveolar macrophages. If microorganisms are not contained/eliminated by host defenses, the pathogen(s) may descend to the alveolar sacs of the lung and infection may ensue.

Microaspiration of oropharyngeal secretion occurs in all people, usually during sleep; however, the normal defense mechanisms described above prevent colonization or infection of the lower respiratory tract in the normal host. This same process may lead to pneumonia in the vulnerable host. A major aspiration of the oropharyngeal or gastric contents may lead to pneumonia or chemical (acid) pneumonitis in the hospitalized and/or compromised host. Dysphagia is a common risk factor for the development of aspiration pneumonia. Dysphagia can be caused by stroke or other neurologic disorders, seizures, or alcoholism. Other factors that may lead or predispose to aspiration pneumonia are: (1) oropharyngeal colonization altered by oral/dental disease; (2) poor oral hygiene; (3) tube feedings; or (4) medications. These factors as well as hospitalization itself may result in colonization of the nasopharynx with organisms from the hospital environment which often exhibit a higher degree of antimicrobial resistance than the usual normal flora. Other risk factors for the development of health care-associated pneumonia include intubation/mechanical ventilation and aspiration.

Once breakdown of the local host defenses occurs and organisms invade the lung tissue, an inflammatory response is generated either by the exotoxins produced by the organism or by the immune response to the presence of the organisms. This inflammatory response can remain localized in the lung (and potentially cause tissue damage) or become systemic.

Clinical Presentation

Clinical symptoms associated with pneumonia are both respiratory and nonrespiratory. With increasing age, both respiratory and nonrespiratory symptoms decrease in frequency.

Symptoms of pneumonia include:

1. Respiratory: cough (productive or nonproductive), shortness of breath, difficulty breathing

2. Nonrespiratory: fever, fatigue, sweats, headache, myalgias, mental status changes

Signs of pneumonia include:

1. Fever. Temperature may increase or decrease from baseline, but most often is elevated.

2. Respiratory rate is increased. Cyanosis, increased respiratory rate, and use of accessory muscles of respiration are suggestive of severe respiratory compromise.

3. Breath sounds may be diminished.

4. Confusion, lethargy, and disorientation are common in elderly patients.

Scoring systems are available for assessing the severity/mortality of the pneumonia and are used to determine not only severity, but site of care (inpatient or outpatient), and treatment. Examples of the scoring systems include the Pneumonia Severity Index (PSI); Confusion, Urea, Respiratory Rate, and Blood Pressure (CURB); and CURB-65 (those 65 years of age and older).

Diagnosis

Key parameters for the diagnosis of pneumonia include the clinical presentation, diagnostic tests, laboratory tests, and microbiology tests.3 Key diagnostic tests for pneumonia include: chest x-ray, oxygen saturation, and arterial blood gases. In addition to a constellation of suggestive clinical features, a demonstrable infiltrate by chest radiograph or other imaging technique is required for the diagnosis of pneumonia. The chest x-ray would reveal single or multiple infiltrates in a patient with pneumonia. Oxygen saturation and arterial blood gases would be obtained to evaluate gas exchange in select patients. Laboratory tests obtained to aid in the diagnosis or treatment of patients with pneumonia include: the white blood cell (WBC) count and basic metabolic panel (BMP). Serum creatinine (SCr) is obtained from the basic metabolic panel and needed to dose many antibiotics appropriately. Microbiologic tests that may be utilized in patients with pneumonia include:

1. Gram stain of respiratory secretions.3,6 A sputum gram stain should demonstrate the presence of WBCs and few squamous epithelial cells. It will also reveal if the bacteria are gram-positive or gram-negative and the morphology (eg, cocci or bacilli). For patients with severe pneumonia, bronchoscopy may be performed to obtain tracheal secretions. Tracheal secretions are better culture specimens compared to sputum cultures because they lack oral contamination.

2. Culture and susceptibility (C&S) tests.3,6 C&S tests (sputum and/or blood cultures) may reveal the genera and species of the bacteria and the degree of susceptibility of the bacteria to antimicrobials (susceptible/intermediate/resistant) and, in some institutions, the minimum inhibitory concentration (MIC). C&S reports are not routinely ordered for outpatient pneumonia cases.

3. Serology (IgM and IgG) is useful in determining the presence of atypical pathogens such as Mycoplasma and Chlamydia.3

4. Urinary direct fluorescence antigen is used to diagnose Legionella pneumophila.

Health care-associated pneumonia is divided into two subsets, early and late onset. The major difference in early and late onset is time of onset/diagnosis (<5 days vs ≤5 days since admission to hospital). Those with late onset HCAP are at risk for infection with multidrug resistant (MDR) organisms (Figure 21-1) for a host of reasons.4 Patients with early onset HCAP are usually infected with organisms common to community-acquired pneumonia.

Prevention of some cases of pneumonia is possible though the use of vaccines and infection control/prevention measures. A polyvalent polysaccharide vaccine is available for one of the leading causes of bacterial pneumonia, Streptococcus pneumoniae.3,7 Influenza vaccine is also effective in preventing pneumonia and should be offered to persons at hospital discharge or during outpatient treatment during the fall and winter.3,8 Smoking cessation should be a goal as smoking is associated with a substantial risk of pneumococcal bacteremia. Respiratory hygiene measures, including the use of hand hygiene and masks or tissues for patients with cough, should be used in outpatient settings and emergency departments as a means to reduce the spread of respiratory infections. There are also recommendations for preventing health care-associated pneumonia (infection control measures, patients should be kept in semirecumbent position, and enteral nutrition is preferred over parenteral).4

The goal of antimicrobial treatment is to eliminate the patient's symptoms, minimize or prevent complications, and decrease mortality.2-4 Treatment of bacterial pneumonia involves the empirical use of a relatively broad-spectrum antimicrobial(s) that is effective against probable pathogens. Antimicrobials exhibiting activity against the suspected pathogens without having activity against nontargeted pathogens is preferred. Table 21-1 lists the common bacterial pathogens associated with the different classifications of pneumonia.2-4 Numerous antimicrobials are available, and the majority are effective in the treatment of bacterial pneumonia. Superiority of one antibiotic over another when both demonstrate similar in vitro activity and tissue distribution characteristics is difficult to define.

The response and outcome of patients with pneumonia depend on the microbial agent involved and the patient status at presentation. Poor prognostic factors include age greater than 65 years; coexisting disease such as diabetes, renal failure, heart failure, or chronic obstructive pulmonary disease (COPD); multiple lobes involved; bacteremia; alcoholism; and neutropenia.3-4 Most patients with pneumonia improve clinically (decreased temperature and systemic symptoms) 24 to 48 hours after the initiation of effective antibiotic therapy. Chest radiograph resolution lags, taking up to 3 weeks in healthy young adults and 12 weeks in elderly patients and those with complicated infections. Tables 21-2 and 21-3 list recommended empiric treatment options for community-acquired and health care-associated pneumonia. Once the etiology of the pneumonia has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at the pathogen. Antimicrobial treatment of aspiration pneumonia consists of: amoxicillin/clavulanate or clindamycin. Table 21-4 lists key parameters for antimicrobials recommended for treatment of pneumonia.

Duration of Treatment

The duration of therapy for pneumonia should be kept as short as possible and depends on several factors: type of pneumonia, inpatient or outpatient status, patient comorbidities, bacteremia/sepsis, and the antibiotic chosen. Patients with community-acquired pneumonia (CAP) and aspiration pneumonia should be treated for a minimum of 5 days (range 5-10 days). Antimicrobials indicated for 5 days of treatment include levofloxacin and azithromycin, the duration for all other agents is 7 to 10 days. Patients should be afebrile for 48 to 72 hours and should have no more than one CAP-associated sign of clinical stability (Table 21-5) before discontinuation of treatment. A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection (meningitis or endocarditis). Patients with health care-associated pneumonia should be treated for 8 to 21 days, depending on severity of the disease and response to therapy.

Health Care-Associated Pneumonia

When feasible, a lower respiratory tract culture needs to be collected from all patients before antibiotic therapy for health care-associated pneumonia, but collection of cultures should not delay the initiation of therapy. Negative lower respiratory tract cultures for 72 hours can be used to stop antibiotic therapy. Early, appropriate, broad-spectrum antimicrobial therapy should be prescribed with adequate doses to optimize therapy.

Antibiotic Resistance Issues

Resistance to commonly used antibiotics for pneumonia presents a major consideration in choosing empirical therapy. Resistance patterns vary by geography. Therefore, antibiotic recommendations must be modified on the basis of local susceptibility patterns.

Drug-Resistant Streptococcus Pneumonia

The emergence of drug-resistant Streptococcus pneumonia (DRSP) is well documented but the clinical significance is uncertain. Few well controlled studies have evaluated the impact of in vitro resistance on clinical outcomes of pneumonia caused by DRSP. Current levels of beta-lactam resistance do not generally result in CAP treatment failures when appropriate agents (amoxicillin, ceftriaxone, cefotaxime) and doses are used. Available data suggest that clinically relevant level of penicillin resistance is a MIC of at least 4 mg/L. Data exist suggesting that resistance to macrolides, ciprofloxacin, and levofloxacin results in clinical failure. Risk factors for infection with beta-lactam resistant S. pneumonia include:

• Age < 2 years or > 65 years
• Beta-lactam therapy within the previous 3 months
• Alcoholism
• Various comorbidities (eg, underlying cardiopulmonary disease)
• Immunosuppressive illness or therapy
• Exposure to a child in a day-care center

DRSP is the reason high-dose amoxicillin (1 g every 8 hours) and amoxicillin/clavulanate XR (2 g every 12 hours) is recommended for CAP treatment (see Table 21-2—outpatient treatment section).

Bronchitis/Bronchiolitis

Bronchitis and bronchiolitis are inflammatory conditions of the large and small elements of the tracheobronchial tree. The inflammatory process does not extend to the alveoli. Bronchitis frequently is classified as acute or chronic. Acute bronchitis occurs in individuals of all ages, whereas chronic bronchitis primarily affects adults. Bronchiolitis is a disease of infancy. Acute bronchitis is a self-limiting viral illness. Treatment is symptomatic and supportive. Chronic bronchitis is most often caused by cigarette smoking and leads to excessive sputum production and a smoker's cough. Patients with chronic bronchitis develop exacerbations (acute exacerbations of chronic bronchitis [AECB]). Treatment of AECB may require treatment with bronchodilators and, for more severe cases, antimicrobials. Antimicrobial treatment of AECB consists of agents that have activity against S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and M. pneumoniae. Bronchiolitis is an acute viral infection of the lower respiratory tract that affects children. Respiratory syncytial virus (RSV) is the most common cause. Treatment of bronchiolitis is symptomatic and supportive.

Pediatric Bacterial Pneumonia

Pediatric pneumonia is caused by the same bacterial pathogens that cause adult CAP. Fluoroquinolones and tetracyclines should not be used in children. High-dose amoxicillin, amoxicillin-clavulanate, intramuscular ceftriaxone, azithromycin, and clarithromycin are potential agents for use in children.

• The most common infections involving the lower respiratory tract are bronchitis, bronchiolitis, and pneumonia.
• The main classifications of pneumonia are: community-acquired and health care-associated (including aspiration pneumonia).
• The etiology of bacterial pneumonia varies in accordance with the type of pneumonia.
• Viruses are a common cause of pneumonia in adults and children (65%).
• Clinical symptoms associated with pneumonia include respiratory and nonrespiratory.
• Key parameters for the diagnosis of pneumonia include the clinical presentation, diagnostic tests, laboratory tests, and microbiology tests.
• Health care-associated pneumonia is divided into two subsets, early and late onset. The major difference in early and late onset is the time of onset after hospitalization.
• Prevention of some cases of pneumonia is possible through the use of vaccines and infection control/prevention measures.
• Treatment of bacterial pneumonia involves the empirical use of a relatively broad spectrum antimicrobial(s) that is effective against probable pathogens. Antimicrobials exhibiting activity against the suspected pathogens without having activity against nontargeted pathogens are preferred.