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1 CME EARN CATEGORY I CME CREDIT by reading this article and the article beginning on page 48 and successfully completing the posttest on page 53. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of January LEARNING OBJECTIVES List the physical examination findings associated with community-acquired pneumonia (CAP) Identify patients requiring inpatient versus outpatient management Identify the most common pathogens associated with CAP Determine an appropriate plan to treat the most common pathogens in an outpatient Diagnosing and treating CAP in immunocompetent adults Patient presentation, likely etiology, and test results provide the clues PAs need to successfully diagnose and treat community-acquired pneumonia. Greta Vines-Douglas, MSHS, PA-C Within the past decade, the number of deaths in the United States from pneumonia and influenza has decreased significantly. Preliminary data from 2004 lists pneumonia and influenza as the eighth leading cause of death, a decrease of nearly 7.3% from the previous year. 1 Interestingly enough, in the 1930s, pneumonia mortality ranked third, behind heart disease and cancer. 2 However, pneumonia is still the number one cause of death from infectious disease in this country. Because pneumonia is not a reportable disease, estimates of its incidence vary, ranging from 4 to 5 million cases each year. 3 An estimated 10% of patients with diagnosed community-acquired pneumonia (CAP) require hospitalization. 4 Pneumonia is a lung disease characterized by inflammation and consolidation of the lung parenchyma caused by an infection or an irritant. The term community-acquired means that the site of initial infection is not a hospital or health care facility. This distinction community-acquired versus nosocomial has important implications for etiology, management, and predicted morbidity and mortality. Pneumonia is often more severe at the extreme ends of the age spectrum (that is, in infants and the elderly) and in immunocompromised persons. Other persons at high risk include those who have recently had antibiotic therapy or an antibiotic-resistant infection and those with comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), renal failure, heart failure, diabetes, liver disease, cancer, or cerebrovascular disease. 5 Because of the prevalence of pneumonia in the general population, PAs should be acutely aware of how to successfully diagnose and treat this infectious process, thus improving patient outcomes and decreasing the need for hospitalization. ANATOMY AND PHYSIOLOGY Pneumonia is an acute condition that manifests as fluid accumulation and inflammation around or within the alveoli, subsequently impairing gas exchange. The disease is primarily the result of inhaling a pathogen. Secondarily, pneumonia may ensue after infection with a noxious agent or via hematogenous spread. The alveolocapillary membranes begin to Computer-enhanced chest radiograph showing pneumonia (pink) SPL / Photo Researchers, Inc. 26 JAAPA JANUARY (1)

2 fill with blood and fluid, which produces the clinical signs found on physical examination and radiographs. Pneumonia may be localized, as in lobar pneumonia, or consist of scattered areas of consolidation. Neutrophils, macrophages, and mucociliary action are essential to prevent damage from the pathogen. Virulent organisms, smoking, chronic lung or heart conditions, superinfection following a recent viral infection (such as influenza), or an immunocompromised state can decrease the body s normal defense mechanisms, thus increasing a person s susceptibility to lung infection. Typical and atypical are terms used to define the presentation of pneumonia symptoms. Typical CAP usually manifests as an acute onset of classic symptoms including fever, productive cough, shortness of breath, signs of pulmonary consolidation (dullness, increased fremitus, egophony, bronchial breath sounds, rales), and, sometimes, pleuritic chest pain. 6 Atypical CAP will often manifest as a gradual onset of lung and extrapulmonary symptoms including mild fever, cough (with or without sputum), myalgias, headache, sore throat, fatigue, and GI upset. 7 Although pneumonias caused by the different common pathogens have distinguishing features, determining the specific pathogen on the basis of clinical, radiologic, and laboratory findings is difficult and usually is done retrospectively, if at all. 7 In addition, elderly patients may present with few respiratory signs and symptoms. Pneumonia manifests in these patients as delirium, a worsening of chronic confusion, or frequent falls. 8 Typical pneumonias Many bacteria may cause pneumonia, but the majority of infections are caused by only a few organisms. Streptococcus pneumoniae is the most common causative pathogen of CAP. S pneumoniae is associated with more severe disease than that caused by other pathogens. 9 S pneumoniae is also the most common bacterial pathogen cultured from hospitalized adults with CAP. 10 Approximately 70% of CAP cases are caused by this organism. 7 Patients infected with S pneumoniae often present with classic pneumonia symptoms. Haemophilus influenzae most commonly causes CAP in elderly patients and in persons with chronic lung diseases. 10 H influenzae is often the causative pathogen found in smokers with CAP. Atypical pneumonias Mycoplasma pneumoniae most commonly causes atypical pneumonia; onset is usually insidious. 7 Ambulatory young adults are most often infected with M pneumoniae, but this pathogen also can cause pneumonia in the elderly. Worldwide, approximately 10% of patients with CAP are infected with Chlamydia pneumoniae. 11 Unlike other respiratory infections that have a peak incidence during the winter months, C pneumoniae infection does not vary significantly The purpose of initial outpatient therapy is to optimize patient outcome and minimize antibiotic resistance at a reasonable cost. by season. This pathogen is most commonly found in persons older than 65 years. 12 The organism can cause persistent latent infection and symptoms. Legionella pneumophila is not commonly seen in patients outside of the hospital and most frequently infects elderly patients and persons with impaired cellular immunity. Person-to-person spread has not been reported. Legionella are found most often in fresh water systems, such as ponds or creeks; in plumbing and other types of man-made water systems; and in moist soil. Legionella infection manifests as a wide array of signs and symptoms that range from mild to severe, including high fever, altered mental status, and respiratory failure. 7 DIAGNOSTIC TOOLS The diagnosis of pneumonia is largely a clinical one. The physical examination findings are usually enough to establish the diagnosis, which is confirmed with a chest radiograph. Radiographic images also can distinguish between CAP and other illnesses or infections that mimic pneumonia. In some cases, the history and physical examination suggest pneumonia, but the radiograph may be negative. 13 According to the American Thoracic Society (ATS) guide- KEY POINTS Pneumonia is defined as a lung disease characterized by inflammation and consolidation of the lung parenchyma caused by an infection or an irritant. The term community-acquired means that the site of initial infection is not a hospital or health care facility. Typical CAP usually manifests as an acute onset of classic symptoms: fever, productive cough, shortness of breath, signs of pulmonary consolidation (dullness, increased fremitus, egophony, bronchial breath sounds, rales), and, sometimes, pleuritic chest pain. Atypical CAP will often manifest as a gradual onset of lung and extrapulmonary symptoms including mild fever, cough (with or without sputum), myalgias, headache, sore throat, fatigue, and GI upset. Once the diagnosis of pneumonia is established, the next important decision is whether to hospitalize the patient. This decision is based on an assessment of disease severity and morbidity and mortality risk. COMPETENCIES Medical knowledge Interpersonal & communication skills Patient care Professionalism Practice-based learning and improvement Systems-based practice JANUARY (1) JAAPA 27

3 CME Community-acquired pneumonia TABLE 1. PSI scoring system Patient characteristic Points assigned Demographic factors Female Age (y) 10 Male Age (y) Nursing home resident +10 Comorbid diseases Neoplastic disease +30 Liver disease +20 Cerebrovascular disease +10 Heart failure +10 Renal disease +10 Physical examination findings Altered mental status +20 Respiratory rate 30 breaths/min +20 Systolic BP <90 mm Hg +20 Pulse 125 beats/min +15 Temperature <35 C or 40 C +15 Laboratory results ph < BUN 30 mg/dl +20 Sodium <130 meq/l +20 Glucose 250 mg/dl +10 Hematocrit <30% +10 Pleural effusion +10 Po 2 <60 mm Hg +10 Adapted with permission from Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. New Engl J Med. 1997;336(4): Copyright 1997 Massachusetts Medical Society. All rights reserved. lines for the management of adults with CAP, sputum should be obtained for culture and Gram s stain if drugresistant bacteria or an organism not usually covered by empiric therapy options is the suspected causative pathogen. 13 However, reliable sputum culture results require a properly collected specimen, which can be difficult to obtain in the outpatient setting. Blood cultures are generally not recommended for outpatient management of CAP because patients can be found to be hypoxemic even in the absence of risk factors. 14 Therefore, arterial blood gases and pulse oximetry results are used to determine the severity of primary organ impairment. Once the diagnosis of pneumonia is established, the next important decision is whether the patient should be hospitalized. This decision is based on an assessment of disease severity and morbidity and mortality risk. The Pneumonia Severity Index (PSI) is a prediction tool used to identify mortality risk in patients with CAP. 15 This tool is recommended by the Infectious Diseases Society of America (IDSA) as a supplement for clinical decision making. 16 The PSI is espe- cially useful in the hospital, where blood test results can be reviewed relatively quickly. The PSI is a scoring system that assigns points to patient history and physical examination findings, and to laboratory test results (see Table 1). The scores separate patients into five categories that reflect the risk of death within 30 days. The PSI first seeks to establish if a patient falls into the lowest risk category, class I 15 (see the algorithm Prediction model for class I pneumonia ). Class I patients have a very low risk of mortality and can therefore be treated as outpatients. Patients not in class I are further stratified into classes II to V 15 (see Table 2). Patients in classes II and III usually do not require hospitalization. Conversely, patients in classes IV and V need to be hospitalized. 16 The PSI is an extremely useful tool, but ultimately clinicians must also consider confounding factors such as a patient s ability to adhere to treatment recommendations at home. Important factors to consider when deciding on outpatient treatment are if the patient has a mental disorder, is a substance abuser, or needs a skilled caregiver. 17 The differential diagnosis for pneumonia is broad. When abnormal findings on lung examination lead to a suspicion of pneumonia, the clinician should always consider heart disease as a possible cause and assess the patient for cardiac disease risk factors. Viruses, COPD, fungi, and fibrosis are also possible causes of abnormal lung examination findings. Other diagnoses include lung abscess, tuberculosis, pleural effusion, or obstruction. 13 A carefully detailed history and imaging studies will help to rule these conditions in or out. TREATMENT GUIDELINES The goal of initial outpatient therapy is to optimize patient outcome and minimize antibiotic resistance at a reasonable cost to the patient and society. 10 The rationale comes from the most likely causative organism, the characteristics and spectrum of antibiotic coverage, and resistance patterns. Special concern needs to be given to modifying risk factors that increase the risk of infection with penicillin-resistant and drug-resistant pneumococci. Modifying risk factors include age older than 65 TABLE 2. Stratification of PSI score Recommended Risk Class Total points treatment site Low I ne Outpatient Low II 70 Outpatient Low III Outpatient Moderate IV Inpatient High V >130 Inpatient Data from Kleinpell RM et al, 6 and Fine MJ et al JAAPA JANUARY (1)

4 years; administration of beta-lactam therapy within the past 3 months; alcoholism; immunosuppression, including that due to therapy with corticosteroids; multiple comorbidities; and exposure to a child attending a day-care center. 13 The treatment guidelines for CAP established by ATS and IDSA are reviewed in this article. Medical organizations in Canada, Spain, England, and Japan also have presented treatment guidelines for CAP; however, a comparison of these guidelines is beyond the scope of this review. ATS guidelines Outpatients with no cardiopulmonary disease or modifying risk factors should be treated with an advanced-generation macrolide (azithromycin or clarithromycin) or doxycycline. Those patients with cardiopulmonary disease or modifying risk factors should be treated with a beta-lactam antibiotic (oral cefpodoxime, cefuroxime, highdose amoxicillin, or amoxillin/clavulanate) or parenteral ceftriaxone followed by oral cefpodoxime plus a macrolide or doxycyline. Alternatively, this higher risk group may be treated with a fluoroquinolone alone. 13 IDSA guidelines Previously healthy outpatients who have not recently received antibiotic therapy should be treated with a macrolide (erythromycin, clarithromycin, or azithromycin) or doxycycline. Outpatients who have received antibiotic therapy within the past 3 months should receive a fluoroquinolone alone, an advanced macrolide plus high-dose amoxicillin, or an advanced macrolide plus high-dose amoxicillin/clavulanate. Outpatients with comorbidities (COPD, diabetes, renal or heart failure, or malignancy) who have not recently received antibiotic therapy should be treated with an advanced macrolide or respiratory fluoroquinolone. Outpatients with comorbidities who have recently received antibiotic therapy should be given a fluoroquinolone alone or an advanced macrolide plus a beta-lactam. 18 Patients should respond to therapy within 72 hours. Patients who show minimal to no improvement may be candidates for hospital admission and further diagnostic workup. TREATMENT CONTRAINDICATIONS Macrolide antibiotics should be used cautiously in patients with renal insuffiency; these agents also may cause QT elongation. Generally, risk of adverse reactions and GI upset is greater with erythromycin; therefore, the newer macrolides are preferred. Erythromycin also is less effective against H influenzae. The newest macrolide, telithromycin, must be used cautiously. Patients with myasthenia gravis should not use this antibiotic. In addition, mild to severe liver damage is possible because of telithromycin s interaction with drugs metabolized through the hepatic cytochrome P450 pathway. Mild to severe allergic reactions also may occur. Macrolides are effective against the most common typical and atypical pathogens; however, pneumococcal resistance to macrolides may be increasing. Beta-lactam antibiotics can cause mild to severe allergic responses, as well as hepatotoxicity, pulmonary problems, GI upset, and neurologic problems. Beta-lactam antibiotics are inactive against atypical pathogens. ALGORITHM. Prediction model for class I pneumonia Is the patient older than age 50 years? Does the patient history include any of these coexisting conditions? Cerebrovascular disease Heart failure Liver disease Neoplastic disease Renal disease Do the physical examination findings include any of these abnormalities? Altered mental status Pulse: 125 beats/min Respirations: 30 breaths/min Systolic BP: <90 mm Hg Temperature: <35 C or 40 C Patient is assigned to risk class I Patient is assigned to risk class II-V, according to PSI score. a a See Table 1 for scoring system and Table 2 for stratification of score. Adapted with permission from Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. New Engl J Med. 1997;336(4): Copyright 1997 Massachusetts Medical Society. All rights reserved. Doxycycline is contraindicated for pregnant women. Significant allergic, GI, neurologic, hematologic, and cardiovascular reactions have occurred. Drugs that doxycycline interacts with include, but are not limited to, anticoagulants, phenytoin, barbiturates, antacids, some antilipid drugs, and carbamazepine. Doxycycline is generally well tolerated and inexpensive, and it is effective against S pneumoniae, H influenzae, atypical agents, and some bioterrorism agents. Fluoroquinolones are not used in children or in pregnant women. Commonly reported side effects include GI symptoms, rash, joint pain, QT elongation, hepatotoxicity, hematologic changes, and hypoglycemia or hyperglycemia. Fluoroquinolones may also affect the CNS when given with NSAIDs. These drugs cover typical and atypical agents and have a relatively low incidence of drug resistance. Continued on page 30 JANUARY (1) JAAPA 29

5 CME Community-acquired pneumonia PREVENTION The adult antipneumococcal vaccine should be given to atrisk patients, including persons older than 65 years; persons aged 19 to 64 years with diabetes, chronic lung or heart disease, alcoholism, chronic liver disease, CSF leaks, or cochlear implants; and persons living in chronic care facilities. In addition, an annual flu vaccination is warranted in high-risk groups because the flu increases the risk that bacterial lung infection will develop. Target groups include persons older than 50 years, children aged 6 months to 5 years, persons with chronic medical conditions, immunosuppressed patients, residents of long-term care facilities, and patients whose ability to clear salivary and/or lung secretions is impeded. In addition, health care workers and other staff employees who can easily spread the flu to others also should receive the vaccine. JAAPA Greta Vines-Douglas practices at Family Care Specialists, Montebello, California, and is an instructor at Western University of Health Sciences, Pomona, California. She has indicated no relationships to disclose relating to the content of this article. DRUGS MENTIONED Amoxicillin Amoxillin/clavulanate (Augmentin) Azithromycin (Zithromax) Carbamazepine Cefpodoxime (Vantin) Ceftriaxone (Rocephin) Cefuroxime (Ceftin, Zinacef) Clarithromycin (Biaxin) Doxycycline (Doryx, Monodox, Vibramycin) Erythromycin (ERYC, Ery-Tab, PCE) Phenytoin (Dilantin, Phenytek) Telithromycin (Ketek) REFERENCES 1. Miniño AM, Heron MP, Smith BL. Deaths: preliminary data for Natl Vital Stat Rep. 2006; 54(19): Podolsky SH. The changing fate of pneumonia as a public health concern in 20th century America and beyond. Am J Public Health. 2005;95(12): Niederman MS, McCombs JS, Unger AN, et al. The cost of treating community-acquired pneumonia. Clin Ther. 1998;20(4): Sue DY. Community-acquired pneumonia in adults. West J Med. 1994;161(4): Lutfiyya MN, Henley E, Chang LF, Reyburn SW. Diagnosis and treatment of community-acquired pneumonia. Am Fam Physician. 2006;73(3): Kleinpell RM, Elpern EH. Community-acquired pneumonia: updates in assessment and management. Crit Care Nurs Q. 2004;27(3): Thibodeau KP, Viera AJ. Atypical pathogens and challenges in community-acquired pneumonia. Am Fam Physician. 2004;69(7): Marrie TJ. Community-acquired pneumonia in the elderly. Clin Infect Dis. 2000;31(4): File TM, Garau J, Blasi F, et al. Guidelines for empiric antimicrobial prescribing in communityacquired pneumonia. Chest. 2004;125(5): Cunha BA. Empiric therapy of community-acquired pneumonia: guidelines for the perplexed? Chest. 2004;125(5): Kuo CC, Jackson LA, Campbell LA, Grayston JT. Chlamydia pneumoniae (TWAR). Clin Microbiol Rev. 1995;8(4): Marrie TJ. Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults. UpToDate Online Web site. inf/10776&view=text. Accessed vember 13, Niederman MS, Mandell LA, Anzueto A, et al; American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163(7): Levin KP, Hanusa BH, Rotondi A, et al. Arterial blood gas and pulse oximetry in initial management of patients with community-acquired pneumonia. J Gen Intern Med. 2001;16(9): Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. New Engl J Med. 1997;336(4): Mandell LA, Bartlett JG, Dewell SF, et al; Infectious Diseases Society of America. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37(11): Coughlin L. ACCP releases consensus statement on outpatient treatment for CAP. Am Fam Physician. 2005;72(8): , File TM Jr. Treatment of community-acquired pneumonia in adults. Up To Date Online Web site. Accessed vember 13, JAAPA JANUARY (1)

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