Community-acquired pneumonia in adults

Prim Care Clin Office Pract 30 (2003) 155 171 Community-acquired pneumonia in adults Julio A. Ramirez, MD a,b, * a Department of Medicine, University of Louisville School of Medicine, 512 S. Hancock Street, Carmichael Building, Room 208-D, Louisville, KY 40202, USA b Department of Veterans Affairs Medicine Center, 800 Zorn Avenue, Louisville, KY 40206, USA Community-acquired pneumonia (CAP) is a serious respiratory tract infection that is routinely managed by primary care physicians. In the United States, pneumonia is the sixth leading cause of death and the number-one cause of death from infectious diseases. It is estimated that up to 5.6 million cases of CAP occur annually, and as many as 1.1 million of these cases require hospitalization. The incidence of CAP is weighted heavily toward the winter months [1,2]. The mortality rate of pneumonia remains low in the outpatient setting, with a mortality range of less than 1% to 5%, but among patients with CAP who require hospitalization, the mortality rate averages 12% overall. For the hospitalized patient with serious CAP requiring admission in the intensive care unit, the mortality may reach 40% [1,2]. Pathogenesis and clinical presentation Pneumonia indicates an inflammatory process of the lung parenchyma that is caused by a microbial agent. The most common pathway for the microbial agent to reach the alveoli is by microaspiration of oropharyngeal secretions. Once microorganisms reach the alveolar space, to cause pneumonia, they must overcome the last defense mechanism of the lung, the alveolar macrophage. Most of the time the alveolar macrophage will phagocytize and kill the microorganisms that reach the alveolar space, which explains why the presence of clinical pneumonia is infrequent, even though the arrival of microorganisms to the alveolar space is not an infrequent occurrence. * Department of Veterans Affairs Medicine Center, 800 Zorn Avenue, Louisville, KY 40206, USA. E-mail address: j.ramirez@louisville.edu 0095-4543/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/s0095-4543(02)00076-3

156 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 If the alveolar macrophage is unable to control the growth of the microorganisms, then as a final protective defense mechanism, the lungs develop a local inflammatory response. This local inflammatory response is characterized by movement of white blood cells, lymphocytes, and monocytes from the capillaries into the alveolar space. The recruitment of phagocytic cells to the alveolar space is mediated primarily by tumor necrosis factor and interleukin-1 produced by the alveolar macrophages. In addition to tumor necrosis factor and interleukin-1, other important locally produced cytokines include interleukin-6, interleukin-10, interleukin-12, monocyte chemotactic factor 1, and granulocyte colony-stimulating factor [3]. Once these cytokines reach the systemic circulation, they also produce a systemic inflammatory response. The local and systemic inflammatory response is responsible for most of the signs, symptoms, and laboratory abnormalities that characterize the CAP syndrome. The patient with pneumonia syndrome presents with cough, sputum production, shortness of breath, pleuritic chest pain, fever, chills, tachycardia, tachypnea, rales, and signs of consolidation on physical examination, and leukocytosis, left shift, and a new pulmonary infiltrate on chest radiograph. Several of these abnormalities are due to the local inflammatory response produced by the arrival of white blood cells into the alveolar space. The development of cough and sputum production are caused by the excess of white blood cells in the alveoli. The shortness of breath and hypoxemia are secondary to the accumulation of cells in the alveolar space producing a ventilation-perfusion mismatching. The presence of a new pulmonary infiltrate on the chest radiograph is predominately attributable to the buildup of inflammatory cells in the alveoli. Other manifestations of the pneumonia syndrome are due to the systemic inflammatory response. The presence of fever is mediated primarily by the action of interleukin-1 and other mediators that act over the thermoregulatory center at the level of the hypothalamus. The presence of leukocytosis and left shift is mediated primarily by the action of granulocyte colonystimulating factors over the bone marrow. Because the clinical and laboratory presentation of patients with CAP is caused mostly by the host inflammatory response, the clinical presentation itself is not characteristic of any particular etiologic agent. It is no longer recommended to consider a patient as having a typical or atypical etiology of CAP based on the patient s clinical presentation. Clinical diagnosis Because of their low sensitivity and specificity, history and physical examination are considered suboptimal to confirm or exclude the diagnosis of CAP [4]. National guidelines recommend that a new pulmonary infiltrate on a chest radiograph should be present to classify a hospitalized patient as

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 157 having the diagnosis of CAP [1,2]. The clinical diagnosis requires evidence of a new pulmonary infiltrate compatible with pneumonia associated with other signs and symptoms characteristic of the pneumonia syndrome. Because the clinical diagnosis of CAP is based on a clinical syndrome, it is expected that in some hospitalized patients with a clinical diagnosis of CAP, an alternative diagnosis will explain the signs and symptoms of the patient. Sometimes the patient may have cough, sputum production, and fever; however, the infection may not represent pneumonia but rather acute exacerbation of chronic bronchitis or acute bronchitis. In this type of patient, there is no evidence of a new pulmonary infiltrate. In patients with a pulmonary infiltrate at admission to the hospital, the pulmonary infiltrate may not represent a new infiltrate but a chronic infiltrate representing old pulmonary changes. In some patients with a new pulmonary infiltrate, the infiltrate may be attributable to an alternative diagnosis, such as pulmonary embolism. In a study performed in the author s institution, it was found that the most common clinical scenario that is associated with a misdiagnosis of CAP is the patient admitted to the hospital with cough and a new pulmonary infiltrate that are due to an exacerbation of congestive heart failure [5]. Need for hospitalization During the initial evaluation of the patient with CAP, physicians need to define the patient s severity of disease and the intensity of care that will be necessary for the patient to achieve an optimal outcome. If the level of care that the patient can receive at home is not sufficient, the patient requires hospitalization. Hospitalization permits the use of intravenous antibiotics, intravenous fluids, hemodynamic support, supplemental oxygen, mechanical ventilation, and aggressive therapy for comorbidity and facilitates several clinical evaluations during the day performed by nurses and physicians. Hospitalization based on patient s risk for mortality A two-step prediction rule to identify low-risk patients with CAP was derived using data from 14,199 adults with CAP [6]. To parallel physician decision-making processes, the prediction rule was developed in two steps. Step 1 This step identified a subgroup of patients at low risk for death solely on the basis of their history and physical examination findings. These patients are classified as class I (Table 1). Step 2 The risk of death was quantified in the remaining patients with the same 11 findings used in step 1 plus two demographic factors and seven laboratory or radiographic findings. A scoring system was used to measure the

158 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 Table 1 Step 1 of the pneumonia severity index 1. Age >50 years? 2. Coexisting conditions? 2.1 Neoplastic disease 2.2 Congestive heart failure 2.3 Cerebrovascular disease 2.4 Renal disease 2.5 Liver disease 3. Abnormalities at PE? 3.1 Altered mental status 3.2 HR >125/min 3.3 RR >30/min 3.4 Systolic BP <90 mm Hg 3.5 Temperature <35 Cor>40 C If none of these 11 risk factors is present, the patient is assigned to risk class I. Abbreviations: BP, blood pressure; HR, heart rate; PE, physical examination; RR, respiratory rate. magnitude of association of these factors with mortality and to assign patients a total number of points (Table 2). Based on the total points assigned, patients are classified in risk class II (70 points), risk class III (71 90 points), risk class IV (91 130 points), or risk class V (>130 points). Among the different classes, the mortality rate is 0.1% for class I patients, 0.6% for class II patients, 2.8% for class III patients, 8.2% for class IV patients, and 29.2% for class V patients. Patients 50 years of age or younger who have none of the coexisting illnesses or physical findings identified as class I are considered candidates for outpatient treatment. Importantly, physicians can make this determination on the basis of information obtained from the initial history and physical examination without having to order laboratory tests, which may be costly and time consuming. Patients assigned to risk class II are considered candidates for outpatient therapy. Patients assigned to risk classes III, IV, or V are considered candidates for hospitalization. Hospital-admission decision Even with the availability of risk-stratification data, the admission decision is ultimately an art-of-medicine decision that should be individualized carefully. Nonclinical factors such as patient preference and social considerations also may influence the site-of-care decision. It is important to keep in mind that the decision to hospitalize is not necessarily a commitment to long-term inpatient care. Rather, it is a decision that certain patients should be observed closely until it is evident that their infection is responding to therapy.

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 159 Table 2 Step 2 of the pneumonia severity index: point score according to patient s characteristics 1. Demographic factor Age (y) Men Age Women Age ÿ 10 2. Nursing home resident þ10 3. Coexisting conditions Neoplastic disease þ30 Liver disease þ20 Congestive heart failure þ10 Cerebrovascular disease þ10 Renal disease þ10 4. Physical examination findings Altered mental status þ20 Respiratory rate >30 þ20 Systolic BP <90 þ20 Temperature <35 Cor>40 C þ15 Pulse >125 þ10 5. Laboratory and radiographic findings Arterial ph <7.35 þ30 BUN >30 mg/dl þ20 Sodium <130 mmol/l þ20 Glucose >250 mg/dl þ10 Hematocrit <30% þ10 PaO 2 <60 mm Hg þ10 Pleural effusion þ10 Abbreviation: BUN, blood urea nitrogen. Etiology of community-acquired pneumonia In clinical studies designed to identify the etiology of CAP using reference microbiology laboratories, a specific pathogen is not identified in approximately 50% of the patients [1,2]. In everyday practice, clinicians are expected to encounter pneumonia of unknown etiology in more than half of the hospitalized patients with CAP. The etiology of CAP can be classified into the following four groups: (1) CAP caused by typical or conventional bacteria, (2) CAP caused by atypical bacteria, (3) CAP caused by other agents, and (4) CAP of unknown etiology. The incidence of the most common organisms causing CAP, according to a review of the literature performed by the author, is depicted in Table 3. In an attempt to define if a typical pathogen is the etiology of pneumonia, it is recommended that all patients should have a sputum specimen for gram stain and culture and two sets of blood cultures obtained before the institution of antimicrobial therapy [1,2]. The quality of sputum specimen should be determined by gram stain results. Only sputum specimens that contain a large number of leukocytes and a minimal number of epithelial cells per low-power field should be accepted for bacterial culture. The urinary

160 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 Table 3 Etiology of community-acquired pneumonia based on a review of published articles 1. Typical pathogens 40% 60% Streptococcus pneumoniae 15% 25% Haemophilus influenzae 2% 10% Moraxella catharralis 0% 5% 2. Atypical pathogens 10% 30% Mycoplasma pneumoniae 1% 10% Chlamydia pneumoniae 5% 15% Legionella pneumophila 0% 15% 3. Other pathogens 5% 25% Viral agents 2% 15% Pneumocystis carinii 0% 10% Mycobacterium tuberculosis 0% 10% 4. Unknown etiology 30% 60% antigen test for detection of Legionella pneumophila is recommended in patients with severe CAP who are hospitalized in the intensive care unit [2]. Antimicrobial therapy The primary antibiotic families used to treat CAP are the beta-lactams, macrolides, quinolones, and tetracyclines. In an attempt to help the practicing physician with antibiotic selection, national organizations in the United States and Canada have published guidelines for therapy for patients with CAP [1,2,7,8]. All documents support certain basic principles of antibiotic therapy for patients with CAP. These principles can be summarized as follows: (1) resistant pathogens tend to infect patients with certain clinical risk factors, (2) identification of these risk factors for infection with resistant pathogens allows the classification of patients into different groups, (3) the initial empiric therapy should be tailored to cover only the likely pathogens for a particular group of patients with CAP, (4) initial empiric therapy with a spectrum of activity that is broader than necessary is not appropriate because this practice favors development of pathogen resistance without improving patient outcome, and (5) in hospitalized patients, it is safe to switch from intravenous to oral therapy once there is documented clinical improvement. The list of organisms able to cause CAP is extensive. Using broadspectrum empiric antibiotics to cover all pathogens in all patients is inappropriate, because not all patients are at risk of infection for all possible etiologic agents. In an attempt to limit the list of likely organisms for a particular patient, all guidelines for therapy classify patients into different groups. For each particular group, there is a limited number of organisms likely to cause CAP. Classification of patients into groups allows for a more rational approach to initial empiric therapy. Patients are classified according to the severity of disease, the site of care, and the presence or absence of risk factors for a particular resistant organism.

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 161 Severity of disease and site of care Patients with CAP can be classified initially according to the severity of disease and site of care. Patients with mild disease will be treated as outpatients, patients with moderate disease will be hospitalized and treated in a medical ward, and patients with severe disease requiring cardioventilatory support will be hospitalized and treated in an intensive care unit. Risk factors for resistant organisms The fact that penicillin-resistant Streptococcus pneumoniae (PRSP) is present in a particular region is not an indication that all patients in that region are at similar risk for developing CAP due to PRSP. Based on published studies, one can identify risk factors for PRSP and risk factors for other resistant organisms. Considering the presence or absence of risk factors, one can define the list of likely invading organisms for a particular patient with CAP. Patient with no risk factors A young patient without any risk factors for resistant pathogens is likely to be infected with one of the core organisms: penicillin-susceptible Streptococcus pneumoniae, Mycoplasma pneumoniae, orchlamydia pneumoniae. These three pathogens are considered as a group of core pathogens that can be the etiology of CAP in any patient. Risk factors for penicillin-resistant Streptococcus pneumoniae The risk factors for PRSP include age older than 65 years, being a nursing home resident, alcoholism, recent use of beta-lactam antibiotics, immunosuppression, multiple medical comorbidities, recent hospitalization, or exposure to a child in a day care center. Risk factors for macrolide-resistant Streptococcus pneumoniae Although S. pneumoniae has different mechanisms of resistance for penicillin than macrolides, the strains of S. pneumoniae that are resistant to penicillin are likely to be erythromycin-resistant. Because there is no difference among the macrolides in regard to S. pneumoniae susceptibility, identification of erythromycin resistance is equivalent to resistance for all the macrolide family. Patients with risk factors for infection due to PRSP should be considered to be at risk for infection with macrolide-resistant S. pneumoniae. Risk factors for Haemophilus influenzae and Moraxella catarrhalis The risk factors include a history of smoking or chronic obstructive pulmonary disease (COPD).

162 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 Risk factors for gram-negative Enterobacteriaceae Risk factors for gram-negative Enterobacteriaceae include those who are elderly patients or nursing home residents or those with a history of alcoholism, immunosuppression, recent antibiotic therapy, multiple medical comorbidities, or recent hospitalization. Risk factors for Pseudomonas aeruginosa Patients with COPD complicated with bronchiectasis, chronic broadspectrum antibiotic use, corticosteroid therapy, malnutrition, or neutropenia are at risk for Pseudomonas aeruginosa. Risk factors for anaerobes Patients with a history of alcoholism, poor dental hygiene, suspected large-volume aspiration, or airway obstruction are at risk for anaerobes. Classification of patients Considering the severity of disease, site of care, and the presence or absence of risk factors for a particular resistant organism, patients are classified into groups. A considerable agreement among guidelines can be obtained if patients are classified into five groups (Fig. 1). Ambulatory patients are classified into groups 1 and 2. Patients treated in the medical Fig. 1. Classification of patients based on severity of pneumonia, site of care, and risk factors for resistant organisms.

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 163 ward are classified as group 3. Patients admitted to the intensive care unit are classified into groups 4 and 5. The list of likely organisms able to cause pneumonia increases as the severity of disease increases and the patient moves from group 1 classification with mild CAP requiring outpatient therapy to group 5 classification with severe CAP requiring therapy in the intensive care unit. This increase in likely pathogens with increased severity of disease is due to the likelihood of a greater number of risk factors in patients with more severe CAP. Empiric therapy for the ambulatory patient: groups 1 and 2 According to the presence of risk factors for particular resistant organisms, the ambulatory patients with CAP can be classified into groups 1 and 2 (Fig. 2). These groups define the likely pathogens and optimal empiric oral therapy. Some patients may have risk factors for more than one resistant pathogen. The basic core organisms described in group 1 should be covered by any selected empiric therapy. Group 1 This group includes patients with no risk factors for resistant organisms or patients with smoking and COPD as the only risk factors. Likely organisms in these patients include the core pathogens penicillin-susceptible Streptococcus pneumoniae, Mycoplasma pneumoniae, andchlamydia pneumoniae, with the addition of H. influenzae or M. catarrhalis in smokers with Fig. 2. Likely organisms and empiric antibiotic therapy for patients in groups 1 and 2 (see text for specific antibiotics and details).

164 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 COPD. These patients can be treated with a new-generation macrolide such as clarithromycin or azithromycin. Doxycycline can be selected in regions where S. pneumoniae remains susceptible to tetracyclines. A patient in group 1, without a history of smoking or COPD, can be treated empirically with erythromycin. Because erythromycin has poor activity against H. influenzae, it is not recommended for smokers or patients with COPD. Group 2 This group includes patients with risk factors for PRSP or Enterobacteriaceae. These patients can be treated with monotherapy using a new-generation quinolone (eg, levofloxacin, gatifloxacin, or moxifloxacin). Another appropriate regimen is combination therapy using a beta-lactam (eg, amoxicillin, amoxicillin-clavulanate, cefuroxime, or cefpodoxime) to cover for resistant pathogens, plus a macrolide (eg, erythromycin, clarithromycin, or azithromycin) or tetracycline (eg, doxycycline) to cover for atypical pathogens. Empiric therapy for the patient in the hospital ward: group 3 In an attempt to decrease cost of care, there is a trend to treat patients with mild CAP in the outpatient setting with oral antibiotics. As a consequence, the population of hospitalized patients tends to be elderly with multiple medical comorbidities, with an increasing number of patients who have already failed to respond to outpatient oral antibiotic therapy. It is considered that most hospitalized patients in a medical ward have some of the risk factors for resistant S. pneumoniae or Enterobacteriaceae and can be classified into a single group (Fig. 3). Group 3 This group includes those at risk for PRSP or Enterobacteriaceae. These patients can be treated with monotherapy using an intravenous new-generation quinolone (eg, levofloxacin, gatifloxacin, or moxifloxacin) or with intravenous combination therapy with a beta-lactam, such as a second- or third-generation intravenous cephalosporin (eg, cefuroxime, cefotaxime, ceftriaxone) or beta-lactam, with beta-lactamase inhibitor (eg, ampicillin-sulbactam), plus an intravenous macrolide to cover atypical pathogens. Data are not available to define which initial empiric regimen (quinolone versus beta-lactam plus macrolide) is the one associated with better patient outcome or decreased cost of therapy. If a hospitalized patient has additional risk factors for anaerobes, the anti-anaerobic activity of the initial intravenous empiric therapy should be considered. In this situation, the preferred intravenous quinolone is moxifloxacin and the preferred betalactam is a combination of beta-lactam with a beta-lactamase inhibitor.

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 165 Fig. 3. Likely organisms and empiric antibiotic therapy for patients in group 3 (see text for specific antibiotics and details). Empiric therapy for the patient in the intensive care unit: groups 4 and 5 All patients with severe CAP who require admission to the intensive care unit should be considered at risk for infection with a series of resistant organisms. Patients hospitalized in the intensive care unit can be classified into groups 4 and 5 (Fig. 4). Group 4 This group includes patients likely to be infected with one or more of the following antibiotic resistant organisms: PRSP, Haemophilus influenzae, Moraxella catarrhalis, Enterobacteriaceae, and Legionella spp. These patients can be treated with a combination of a third-generation intravenous cephalosporin (cefotaxime or ceftriaxone) plus an intravenous macrolide (erythromycin or azithromycin), or they can be treated with a combination of a third-generation intravenous cephalosporin (cefotaxime or ceftriaxone) plus an intravenous new-generation quinolone (levofloxacin, gatifloxacin, or moxifloxacin). Group 5 This group includes patients at risk for infection with the resistant pathogens described in group 4 plus risk factors for infection with Pseudomonas aeruginosa. The goal in selecting empiric therapy for this

166 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 Fig. 4. Likely organisms and empiric antibiotic therapy for patients in groups 4 and 5 (see text for specific antibiotics and details). group of patients is to cover the pathogens described in group 4 and to generate a regimen with synergistic activity against Pseudomonas aeruginosa. These patients can be treated with a combination of an intravenous beta-lactam antibiotic with good activity against PRSP and Pseudomonas aeruginosa (eg, imipenem, meropenem, piperacillin/tazobactam, cefepime) plus an intravenous quinolone with good activity against Legionella spp and Pseudomonas aeruginosa (eg, ciprofloxacin). Another option for this group of patients is to achieve combination therapy against P. aeruginosa with a combination of a beta-lactam plus an aminoglycoside, adding a quinolone or a macrolide to cover for Legionella. Timely administration of antibiotics For hospitalized patients with CAP, guideline documents indicate that it is important to give the first dose of antibiotic as soon as possible after hospital arrival. Delayed antibiotic administration in hospitalized patients with CAP is associated with lower outcomes. This concept is based primarily on a large retrospective study performed in the United States that indicated that in patients 65 years or older, those receiving antibiotics within 8 hours of their hospital arrival had a 20% to 30% decrease in 30 days mortality compared with those who received antibiotics after 8 hours of hospital arrival [9]. Although there are no studies to evaluate timing of antibiotic administration in younger patients, it is now recommended that

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 167 all hospitalized patients with CAP should receive the first dose of antibiotic within 8 hours of hospital arrival. Switching from intravenous to oral therapy Expected clinical course If empiric therapy is initiated according to guidelines, most hospitalized patients with CAP show evidence of clinical improvement. The expected course of a hospitalized patient with clinical improvement can be divided into three different periods [10]: a first period when the patient is clinically unstable, a second period of early clinical improvement, and a third period of definitive clinical improvement. The first period starts with the initiation of parenteral antimicrobial therapy. Despite appropriate empiric antimicrobial therapy, most patients remain clinically unstable for 48 to 72 hours. Because of this finding, it is not recommended to change the initial antimicrobial regimen during the first 48 to 72 hours unless there is a marked clinical deterioration. The second period starts when the patient reaches the point of clinical stability. During this second period, the signs, symptoms, and laboratory abnormalities caused by the infection begin to normalize, and the patient shows evidence of initial clinical improvement. During the third period of recovery, the signs, symptoms, and laboratory abnormalities are greatly improved or resolved. When to consider switch therapy The decision regarding when to switch from intravenous to oral antibiotics should be based on the patient s clinical response to therapy. Close evaluation of signs and symptoms such as cough, sputum production, shortness of breath, fever, and leukocytosis identifies the patient who reaches clinical stability. Recent clinical trials have indicated that in hospitalized patients with CAP, the switch to oral therapy can be performed safely once the patient reaches the point of clinical stability and enters the second period of recovery (Fig. 5). A patient can be considered to reach clinical stability and be a candidate for switch therapy when the following four criteria are met: (1) cough and shortness of air are improving, (2) the patient is afebrile (temperature <100 F) for at least 8 hours, (3) the white blood cell count is normalizing, and (4) oral intake and gastrointestinal absorption are adequate [1]. Based on these criteria, most patients reach clinical stability and are candidates for oral therapy during the first 3 days of treatment [11]. Because improvement in the chest radiograph lags behind clinical improvement, it is not recommended to repeat a chest radiograph to evaluate if the patient has reached clinical stability. It is not unusual to have a patient who is clinically improving at the time that the chest radiograph is unchanged or even deteriorating.

168 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 Fig. 5. Time to switch therapy during the recovery phase of patients with CAP. Selection of oral antibiotics Before initiation of initial intravenous empiric therapy, appropriate culture specimens of respiratory secretions and blood are obtained. If the cultures identify the etiology of CAP, the spectrum of initial empiric therapy can be narrowed to cover only the identified pathogen. This change from a broad-spectrum intravenous therapy to a more narrow-spectrum intravenous therapy is defined as known-pathogen therapy or pathogen-directed therapy. In a patient who is clinically improving, the switch from intravenous to oral therapy can be performed from known-pathogen therapy or from empiric therapy (Fig. 6). When the pathogen causing CAP is known, the choice of the oral antimicrobial for switch therapy is based on the susceptibility pattern of the identified microorganism. In patients with CAP, it is unusual to identify a definitive pathogen. As such, the most common scenario is a switch to oral antibiotics from empiric parenteral therapy. In this clinical situation, the oral antibiotic should be equivalent to the intravenous empiric regimen regarding spectrum of antimicrobial activity. Because intravenous antibiotics are discontinued during the early phase of recovery, the patient s compliance with the oral antibiotic regimen is of paramount importance. Patients should be given explicit instructions regarding the potential for drug-drug or drug-food interactions (eg, quinolones-antacids) to avoid reduced absorption of oral antibiotics. Correlation of switch therapy with early hospital discharge Clinical improvement during the initial 3 days of intravenous treatment is seen in a number of hospitalized patients with CAP. The ideal model to

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 169 Fig. 6. Selection of oral antibiotics for switch therapy. decrease treatment cost for the full population of hospitalized patients with CAP is to perform early switch to oral therapy followed by early hospital discharge in a significant number of patients. At least three factors may be present in a population of patients with CAP that will impede this ideal model of early switch to oral therapy followed by early hospital discharge. First, a subgroup of hospitalized patients will deteriorate clinically on empiric intravenous therapy and will not be candidates for oral antibiotics. Second, among the population that responds to intravenous antibiotics, a subgroup of patients will have a late clinical response and will not be candidates for early use of oral antibiotics. Third, even if all patients who show evidence of early clinical improvement during the first 3 days of treatment are switched to oral therapy, hospital discharge may be delayed in some of these patients because of conditions not related to pneumonia. If none of these three factors is present, the patient can be managed with the ideal model of early switch early discharge. In a recent study, it was documented that 65% of hospitalized patients with CAP can be switched to oral therapy during the first 3 days of hospital therapy [11]. It should be expected that almost half of the population of hospitalized patients with CAP can be managed safely with the approach of early switch followed by early discharge. Prevention of community-acquired pneumonia During epidemics of influenza, there is an increase in the frequency of CAP due to primary influenza pneumonia and secondary bacterial

170 J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 pneumonia complicating a case of influenza. Influenza vaccine is effective in limiting the severity of disease caused by the influenza virus. The pneumococcal vaccine has been proven to prevent pneumococcal pneumonia in young adults. The efficacy of the vaccine tends to decline with age and in patients who are immunocompromised. The population of hospitalized patients with CAP should be considered a high-risk population for rehospitalization related to influenza or pneumonia. Hospitalized patients with CAP should be evaluated to define if they are candidates for vaccination, and candidates should be vaccinated before hospital discharge [1,2]. There is no contraindication for the use of the pneumococcal vaccine and the influenza vaccine after an episode of CAP. These vaccines can be given simultaneously at different sites, without increasing side effects [12]. When patients are hospitalized during the influenza season, they can be considered at risk for acquiring influenza from an infected health care worker. The vaccination of health care workers can be seen as an important strategy for the prevention of influenza in vulnerable hospitalized patients. Because smoking is a definitive risk factor for the acquisition of pneumonia, all hospitalized patients with CAP should be advised to be enrolled in a smoking-cessation program in an attempt to prevent relapse of pneumonia. Summary The most common etiologic agent of CAP is Streptococcus pneumoniae. Atypical pathogens are the cause in approximately 20% to 30% of patients. Because the patient s clinical presentation cannot be used to predict if a patient is infected with S. pneumoniae or an atypical pathogen, the initial empiric therapy should cover for these core organisms in all patients. In patients with CAP, the antibiotic spectrum of initial empiric therapy will escalate from an oral macrolide in an ambulatory patient without risk factors for resistant pathogens, to intravenous combination therapy, in a hospitalized patient in the intensive care unit with risk factors for resistant gram-negative organisms. The hospitalized patient can be switched safely from intravenous to oral therapy once he or she reaches clinical stability. The use of pneumococcal vaccine, influenza vaccine, and smoking-cessation programs is an important strategy to prevent CAP. References [1] Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, et al. Guidelines for the management of adults with community-acquired pneumonia. American Thoracic Society. Am J Respir Crit Care Med 2001;163:1730 54. [2] Bartlett JG, Dowell SF, Mandell LA, File TM Jr, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2000;31:347 82.

J.A. Ramirez / Prim Care Clin Office Pract 30 (2003) 155 171 171 [3] Nelson S, Mason CM, Kolls J, Summer WR. Pathophysiology of pneumonia. Clin Chest Med 1995;16:1 12. [4] Wipf JE, Lipsky BA, Hirschmann JV, et al. Diagnosing pneumonia by physical examination: relevant or relic? Arch Intern Med 1999;159:1082 7. [5] Ahkee S, Barzallo M, Ramirez J. Empiric antibiotic therapy in patients without documented infections. Infections in Medicine 1996;13:800 2, 823. [6] Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243 50. [7] Heffelfinger JD, Dowell SF, Jorgensen JH, Klugman KP, Mabry LR, Musher DM, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med 2000;160:1399 408. [8] Mandell LA, Marrie TJ, Grossman RF, Chow AW, Hyland RH. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. The Canadian Community-Acquired Pneumonia Working Group. Clin Infect Dis 2000;31: 383 421. [9] Meehan TP, Fine MJ, Krumholz HM, et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997;278:2080 4. [10] Ramirez JA. Switch therapy in adult patients with pneumonia. Clin Pulm Med 1995;2: 327 333. [11] Ramirez JA, Vargas S, Ritter GW, Brier ME, Wright A, Smith S, et al. Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia. Arch Intern Med 1999;159:2449 54. [12] Fletcher TJ, Tunnicliffe WS, Hammond K, Roberts K, Ayres JG. Simultaneous immunization with influenza vaccine and pneumococcal polysaccharide vaccine in patients with chronic respiratory disease. BMJ 1997;314:1663 5.