Treatment Complications
H.1 Intercurrent Infections

While a variety of noninfectious irritants and allergens can cause acute exacerbations in the patient with COPD, the most frequent and important are the infectious complications. These are extremely variable and range from nonspecific bronchitis to life-threatening pneumonia. The most common infectious complications associated with COPD are:

1. Acute purulent bronchitis.
2. Recurrent chronic bronchitis and bronchiectasis.
3. Community-acquired pneumonia.
4. Mycobacterial and fungal infections.

Acute Purulent Bronchitis

Patients with COPD and acute bronchitis present with increased amounts of purulent secretions, dyspnea, and chest tightness. The organisms most often identified include pneumococcus, hemophilus, and streptococcus. These usually respond to standard “first-line” anti-biotics such as amoxicillin, doxycycline, trimethoprim-sulfamethoxazole, or erythromycin. Not only are these antibiotics effective antimicrobials, but they are the most cost effective. The effectiveness of erythromycin against H. influenzae is variable. The newer macrolides, clarithromycin and azithromycin, are more effective against H. influenzae but are substantially more expensive. These macrolides are also better tolerated and cause fewer gastrointestinal side effects than erythromycin.

Some patients with long-standing COPD become infected with gram-negative organisms (e.g., Klebsiella, Serratia, and Pseudomonas). These require specific treatment with third-generation cephalosporins or quinolones (See Table 4).

Table 4 Empiric Antibiotic Therapy for Acute Purulent Bronchitis

The designation “first-line” implies the most cost-effective antibiotics. The selection of antibiotics must be patient specific. “Second-line” antibiotics are used in cases of allergy to or failure of first-line drugs.

*Dosages assume normal renal and/or hepatic function.

Acute purulent bronchitis should be treated for 7 days. Symptoms usually improve after 3 to 4 days of therapy. Because of associated bronchospasm, the patient's bronchodilator and anti-inflammatory therapy should be maximized. Frequently, this requires the addition of systemic corticosteroids.

If the initial course of therapy with first-line antibiotics fails, then a second course with broad-spectrum antibiotics (such as second- or third-generation cephalosporins, amoxicillin clavulanate, macrolides or quinolones), should be given for an additional 10 days.

Chronic Bronchitis and Bronchiectasis

While patients with chronic bronchitis and bronchiectasis have chronic sputum production, they usually do not require antibiotic therapy. However, when symptoms of cough, sputum production, and dyspnea become so severe that they interfere with the patient's daily performance, “suppressive” antibiotic therapy is helpful. The first-line antibiotics (see above) are used on a once-daily basis for 10 to 14 days and may be rotated every 2 to 4 weeks. Symptomatic superinfection with gram-negative organisms requires therapy with either third-generation cephalosporins or the quinolones.

Community-Acquired Pneumonia

The most serious infectious complication of COPD is pneumonia. In contrast to acute and chronic bronchitis, patients with pneumonia experience worsening symptoms of cough, but with fever, intense dyspnea, and chest discomfort. Posteroanterior and lateral chest radiographs should be done. Because of the anatomical alterations caused by COPD, the chest x-ray may not demonstrate a typical lobar pattern with dense alveolar consolidation. Also, a “Swiss-cheese lung,” mimicking a necrotizing pneumonia, may be apparent.

Establishing the etiology of pneumonia in patients with COPD is often difficult. Routine examination of sputum with gram stain and culture is not always helpful. Some patients are unable to produce adequate sputum samples. In others, the organisms identified may not represent the pathogen. The most common etiological agents along with suggested therapies are listed in Table 5. Although pneumococcal pneumonia remains common, gram-negative organisms (some of which produce beta-lactamase) may be the major pathogens in patients who have recently been hospitalized, who reside in nursing homes, or who have been on previous antibiotic therapy. Pneumococcal vaccine is recommended.

Table 5 Outpatient Pneumonia with Comorbidity

60 Years of Age or Older 1,2

Organisms:

---

S. pneumoniae
Respiratory viruses

H. Influenzae
Aeorobic gram-negative baccilli

S. aureus

Miscellaneous;
E. Pneumoniae, Mycoplasma, Moraxella catarrhalis, Legionella sp.,
M. tuberculosis, endemic fungi

---

Therapy:

Second-generation cephalosporin

OR

Trimethoprim-sulfamethoxazole

OR

Beta-lactam/beta-lactamase inhibitor
±

Erythromycin or other macrolide3

1 Excludes patients at risk for HIV.
2 In roughly one-third to one-half of the cases no etiology was identified.
3 If infection with Legionella sp. is a concern.

Since the severity of illness is greater in COPD patients with pneumonia, broad-spectrum antibiotics (including second- and third-generation antibiotics, newer macrolide antibiotics, and quinolones) should be used. Many patients require hospitalization because of acute respiratory failure (See Section H.4) and should receive the above antibiotics intravenously. In critical patients, aminoglycosides or third-generation cephalosporins, vancomycin, and erythromycin should be administered until a specific etiology is identified.

The “atypical” pneumonias are emerging as important causes of disease in patients with COPD. These include Legionella, Chlamydia pneumoniae, Moraxella catarrhalis, and Mycoplasma pneumoniae. If tolerated, erythromycin remains the drug of choice. Newer macrolides such as clarithromycin and azithromycin are excellent but more expensive. For patients allergic to macrolides, quinolones, or doxycycline should be used.

Viral infections may cause atypical pneumonia and acute exacerbations of COPD. The resolution of viral pneumonia can be complicated by residual bronch-iolitis and bronchiectasis and by increased airflow obstruction. Influenza can be a fatal illness, and all patients with COPD should be given annual influenza vaccinations. While cytomegalovirus and herpes simplex may occur, this usually only happens in patients who are immunosuppressed with large doses of corticosteroids.

Mycobacterial Disease

There has been a dramatic worldwide increase in the incidence of tuberculosis over the past decade. Patients with underlying COPD seem to be more susceptible to atypical mycobacterial disease, and one should always consider the diagnosis of tuberculosis in patents whose chest x-rays show cavitary apical disease. In addition, a nonresolving or slowly progressing infiltrate can be caused by Mycobacterium tuberculosis. Once suspicious of mycobacterial disease, the physician should proceed with the following diagnostic studies:

1. Sputum examination for acid fast bacilli, (afb), smear and cultures.
2. Placement of intermediate strength purified protein derivative, (ppd).
3. Possible bronchoscopy for cultural and histological examinations of bronchial washing, brushing, and biopsy.

Fungal Infections

Fungi remain an important consideration in the differential diagnosis of certain infiltrates in patients with COPD. Depending on geography, specific fungal pathogens must be considered. In the Ohio and Mississippi River Valleys, histoplasmosis is endemic and may cause acute or chronic disease. In the southwestern United States (California and Arizona), coccidioido-mycosis is endemic and can be epidemic following a dust storm. Patients may present with acute respiratory illness with or without pulmonary infiltrates.

Aspergillus is a pathogen that can be extremely dangerous in patients with COPD. Individuals on long-term corticosteroid therapy who have been colonized with Aspergillus are at higher risk for the "semi-invasive" form of infection. Treatment for this difficult disease requires subspecialty consultation and prolonged intravenous therapy. Rarely, patients with COPD may have an element of allergic broncho-pulmonary aspergillosis, but this is usually limited to patients with asthma.

Because of the difficulty in determining the significance of sputum cultures positive for fungi (i.e., infection versus colonization), consultation is usually recommended before initiating specific antifungal therapy.

References

Adams WG, Berk SL. Moraxella catarrhalis: An emerging pathogen. J Respir Dis 1993;14:1352-1360. This article emphasizes that M. catarrhalis, formerly known as Neisseria catarrhalis, is an important pulmonary pathogen in some patients with COPD.

Fein AM, Feinsilver SH, Niederman MS. Nonresolving and slowly resolving pneumonia. Clin Chest Med 1993;14:555-569. This review emphasizes the cause of the slow resolution of pneumonic infiltrations. COPD is one cause of slowly resolving pneumonia.

Mandell GH, Bennett JG, Dolan R. Principles and Practices of Infectious Disease. Churchill-Livingstone: New York, 1995 (4th edition). This full-length text is a general reference on the treatment of infectious disease, including those involving the lungs.

Niederman MS, Campbell GD, Fein AM, et al. Guidelines for the initial management of adults with community-acquired pneumonia: Diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Respir Dis 1993;148:1418-1426. A current set of guidelines for the management of acquired pneumonias, including those encountered in patients with COPD.