PRACTICAL THERAPEUTICS Atypical Pathogens and Challenges in Community-Acquired Pneumonia KRISTOPHER P. THIBODEAU, LCDR, MC, USN, and ANTHONY J. VIERA, LCDR, MC, USNR Naval Hospital Jacksonville, Jacksonville, Florida Atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. Antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. Doxycycline, a fluoroquinolone with enhanced activity against Streptococcus pneumoniae, or a macrolide is appropriate for outpatient treatment of immunocompetent adult patients. Hos- pitalized adults should be treated with cefotaxime or ceftriaxone plus a macrolide, or with a fluoroquinolone alone. The same agents can be used in adult patients in intensive care units, although fluoroquinolone monotherapy is not recommended; ampicillin-sulbactam or piper- acillin-tazobactam can be used instead of cefotaxime or ceftriaxone. Outpatient treatment of children two months to five years of age consists of high-dose amoxicillin given for seven to 10 days. A single dose of ceftriaxone can be used in infants when the first dose of antibiotic is likely to be delayed or not absorbed. Older children can be treated with a macrolide. Hospital- ized children should be treated with a macrolide plus a beta-lactam inhibitor. In a bioterrorist attack, pulmonary illness may result from the organisms that cause anthrax, plague, or tulare- mia. Sudden acute respiratory syndrome begins with a flu-like illness, followed two to seven days later by cough, dyspnea and, in some instances, acute respiratory distress. (Am Fam Physi- cian 2004;69:1699-706. Copyright© 2004 American Academy of Family Physicians) Members of various ommunity-acquired pneu- pneumonia.5 Because M. pneumoniae infec- family practice depart- monia (CAP) affects approxi- tion becomes more common with increasing ments develop articles mately 4.5 million adults in age, it is particularly important to consider for “Practical Therapeu- 1 6 tics.” This article is one the United States annually. this agent in elderly patients. in a series coordinated About one third of these M. pneumoniae infection occurs through- by the Department Cadults require hospitalization.1 The mortality out the year but can cause periodic outbreaks of Family Medicine at rate among hospitalized patients with CAP within small communities. Transmission is Naval Hospital Jack- varies each year and can reach 35 percent.2 by person-to-person contact, and infection sonville, Jacksonville, Fla. Guest editor of While Streptococcus pneumoniae causes up spreads slowly, most often within closed the series is Anthony to 70 percent of CAP cases, atypical patho- populations (e.g., households, schools, busi- J. Viera, LCDR, MC, gens are responsible for 30 to 40 percent nesses). USNR. of cases3 and may be copathogens in other M. pneumoniae is the pathogen most often cases. Even with a knowledge of some of the associated with atypical pneumonia. Onset common characteristics of infections with is insidious, over several days to a week. atypical organisms (Table 1),4 determining Constitutional symptoms, which usually are the specific pathogen on the basis of clinical, present, include headache exacerbated by a radiologic, and laboratory findings is difficult cough, malaise, myalgias, and sore throat. and usually done retrospectively, if at all. The cough is usually dry, paroxysmal, and worse at night. Atypical Pathogens The clinical course of pneumonia caused MYCOPLASMA PNEUMONIAE by M. pneumoniae is usually mild and self- Mycoplasma pneumoniae causes a wide range limited. The mortality rate is approximately of respiratory infections, including pneumo- 1.4 percent.2 However, pulmonary complica- nia, tracheobronchitis, and upper respira- tions can be significant and include effusion, tory tract infection. Only 3 to 10 percent of empyema, pneumothorax, and respiratory persons infected with M. pneumoniae develop distress syndrome. Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. TABLE 1 Diagnostic Features Suggestive of Community- Acquired Pneumonia Caused by Atypical Pathogens Chlamydia Legionella Diagnostic Mycoplasma pneumoniae species feature pneumonia pneumonia pneumonia History Abdominal pain − − + CHLAMYDIA PNEUMONIAE Confusion +/− − + Diarrhea +/− − + Ear pain +/− − − Chlamydia pneumoniae is an obligate intracellular organ- Headache (mild) + − − ism capable of persistent latent infection. Humans are the Myalgias + +/− + only known reservoir. Transmission results from contact Pleuritic pain +/− − + with respiratory secretions, with an incubation period of Sore throat + + − several weeks. Physical signs By the age of 20 years, one half of persons in the United Cardiac +/− − − States have detectable levels of antibody to C. pneumoniae.7 involvement The antibody is present in 75 percent of elderly persons.7 Lobar +/− − +/− C. pneumoniae infection is more likely to occur in older consolidation patients with comorbid diseases than in those who are Hemoptysis − − + otherwise healthy.8 Pharyngitis + + − (nonexudative) Patients with C. pneumoniae infection often present Rash +/− − − with sore throat, headache, and a cough that can persist 9 Raynaud’s +/− − − for months if treatment is not initiated early. Sputum phenomenon is usually scant or nonexistent, and a low-grade fever Chest Patchy Funnel-shaped Patchy is usually present. Chest radiographs tend to show less radiograph infiltrate or consolidation extensive infiltrates than are seen with other causes of circumscribed pneumonia, although significant infiltrates have been infiltrate reported.10 Laboratory Most cases of C. pneumoniae infection are mild, but test results severe disease can occur, necessitating admission to an Cold agglutinins + − − intensive care unit. The mortality rate has been estimated Hyponatremia − − + Leukocytosis +/− − + to be 9 percent, and death usually is associated with sec- 2 Microscopic − − + ondary infection and underlying comorbid disease. hematuria Transaminase − − + LEGIONELLA PNEUMOPHILA elevation Like C. pneumoniae, Legionella species are intracellular organisms. Legionella pneumophila is the most pathogenic − = rarely; +/− = occasionally; + = often. species, and several serotypes have been identified. Sero- Adapted with permission from Cotton EM, Strampfer MJ, Cunha BA. type 1 has been associated with most reported human Legionella and mycoplasma pneumonia—a community hospital experi- cases of pneumonia caused by L. pneumonphila.11 ence with atypical pneumonias. Clin Chest Med 1987;8:441-53. Infection occurs from exposure to legionellae organ- isms in the environment. Person-to-person spread has not been reported. Legionellae are found most commonly in freshwater and man-made water systems. The pathogens M. pneumoniae infection may be associated with sev- also can be found in moist soil, especially near streams eral extrapulmonary manifestations. Skin manifestations and ponds. Man-made systems for heating and cooling include erythema multiforme, erythema nodosum, macu- water can be prime environments for the proliferation of lopapular and vesicular eruptions, and urticaria. Neuro- legionellae, because of conditions such as temperatures logic derangements include aseptic meningitis, cerebral between 32°C (89.6°F) and 45°C (113°F), stagnation of ataxia, encephalitis, Guillain-Barré syndrome, and trans- water, and the presence of scale sediment and amebas.12 verse myelitis. The production of cold agglutinins can result Condensers, cooling towers, respiratory therapy equip- in hemolytic anemia, especially when M. pneumoniae titers ment, showers, water faucets, and whirlpools have been are high. Finally, complications such as myocarditis, pan- associated with outbreaks of legionellosis.13 creatitis, pericarditis, and polyarthritis can occur. Risk factors for the development of legionellosis include 1700-AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 69, NUMBER 7 / APRIL 1, 2004 TABLE 2 Pneumonia Empiric Antibiotic Regimens for Community-Acquired Pneumonia* Outpatient treatment Doxycycline (Vibramycin) or Fluoroquinolone (gatifloxacin [Tequin], levofloxacin [Levaquin], moxifloxacin [Avelox]) with enhanced activity against Streptococcus pneumoniae disease and include headache, muscle aches, anorexia, and or malaise.15 Diarrhea and other gastrointestinal symptoms Macrolide (azithromycin [Zithromax], clarithromycin [Biaxin], are present in 20 to 40 percent of cases.15 Leukocytosis is a erythromycin) common laboratory finding, and the sputum Gram stain Inpatient treatment often shows an abundance of inflammatory cells without a Patient not in intensive care unit 11 Extended-spectrum cephalosporin (cefotaxime [Claforan], predominance of organisms. ceftriaxone [Rocephin]) plus a macrolide Among cases of CAP with atypical causes, legionnaires’ or disease has the most severe clinical course, and illness can Fluoroquinolone alone become progressively more severe if the infection is not Patient in intensive care unit treated appropriately and early. Although extrapulmonary Cefotaxime or ceftriaxone plus a macrolide manifestations are rare, legionellosis has been implicated or in cases of myocarditis, pericarditis, and