1.1. Clinical Relevance
Several advances have occurred in our knowledge of the natural history and management of bronchitis. The first step has been a classification of patients with chronic bronchitis into four groups (see Table 1) (1). Chronic bronchitis is a syndrome defined by cough and production of sputum on most days for at least 3 months a year for 2 consecutive years (2). It is often complicated by airway obstruction leading to the commonly used term chronic obstructive pulmonary disease (COPD).
Acute bronchitis and acute exacerbation of chronic bronchitis account for about 14 million physician visits each year in the United States, making these conditions among the most common illnesses encountered by family physicians (3). Not only is there considerable morbidity from chronic bronchitis, there is also substantial mortality, as chronic obstructive lung disease is the fourth leading cause of death in the United States (4).
Despite the common nature of chronic bronchitis, there has been, and continues to be, considerable controversy about its management. Bacterial infection is but one factor in the production of inflammation in chronic bronchitis, but according to Ball it is fundamental to the vicious circle hypothesis leading to a pattern of repetitive infective exacerbations (5). Haemophilus influenzae seems to be the most important pathogen in chronic bronchitis. Streptococcus pneumoniae and Moraxella catarrhalis are also important. It is noteworthy that there is a correlation between the severity of lung disease as indicated by a forced expiratory volume in 1 s (FEV1) value and the bacterial species recovered during exacerbations of chronic bronchitis. Eller and colleagues (6) found that in patients with an FEV1 of >50% of predicted that about 10% of patients had Enterobacteriaceae or Pseudomonas species isolated from purulent respiratory secretions, and 40% of those who had an FEV1 of <35% of predicted had these bacteria isolated.
From: Infectious Disease in the Aging Edited by: Thomas T. Yoshikawa and Dean C. Norman © Humana Press Inc., Totowa, NJ
Classification of Patients with Chronic Bronchitis
Classification of Patients with Chronic Bronchitis
Previously healthy patient with postviral
Simple chronic bronchitis
Chronic bronchitis plus airflow obstruction
and/or other medical problems such as diabe
tes mellitus, heart failure, and/or elderly
Chronic bronchial sepsis; daily purulent spu
tum production (these patients usually have
bronchiectasis on computed tomographic
examination of the lungs)
For some time it was unclear which population of patients with bronchitis would benefit from antibiotic therapy. It is the clear impression of infectious diseases consultants that antibiotics are overused in the management of patients with bronchitis. A meta-analysis of randomized trials of antibiotics in exacerbations of COPD found a small, but statistically significant, improvement due to antibiotic therapy (7). These investigators found 239 trials published between 1955 and 1994, but only 9 trials met their criteria for inclusion in the analysis. They also noted a summary change in peak expiratory flow rate of 10.75 L/min (95% CI, 4.96- 16.54 L/min) in favor of the antibiotic-treated group. A concept that is now being used in trials of antibiotic therapy for acute exacerbations of chronic bronchitis is time to next relapse (8,9). In a randomized double-blind trial clinical, resolution was noted in 89/99 (90%) of those treated with ciprofloxacin compared with 82% (75/91) of clarithromycin recipients (8). The median infection-free interval was 142 d for ciprofloxacin recipients and 51 d for clarithromycin recipients (P =0.15). Bacteriological eradication rates were superior for ciprofloxacin-treated patients 91% vs 77% (P = 0.01). In a similar trial of cefuroxime axetil vs ciprofloxacin, the clinical resolution rates were similar at 93% and 90%; bac-teriologic eradication rates were higher for ciprofloxacin-treated patients 96% vs 82%, (P <.01). Median infection free interval was 178 d for cefuroxime recipients and 146 d for ciprofloxacin-treated patients (P = 0.37) (9). Given the widespread use of antibiotics to treat bronchitis, several groups have developed guidelines for the treatment of this condition (3). A consensus has now developed that group 1 patients (see Table 1) have acute bronchitis that is usually due to viral infection and do not need antibiotic treatment (3); group 2 patients have mild to moderate impairment of lung function (FEV1 >50%) and have less than four exacerbations per year. Treatment with a P-lactam antibiotic is recommended for this group, as the usual infecting pathogens are H. influenzae, S. pneumoniae, and M. catarrhalis. It is important to remember that about 30% of H. influenzae isolates, and 90% of M. catarrhalis isolates produce P-lactamases and are resistant to ampicillin. Amoxicillin-clavulanic acid as well as second-generation cephalosporins are effective. Group 3 patients are older than group 1 or group 2 patients and have an FEV1 <50% of predicted and or comorbidities such as diabetes mellitus, congestive heart failure, chronic renal failure and the like. They may also experience four or more exacerbations per year. The same organisms as for group 2 patients are involved here as well. The recommendations for antibiotic therapy include amoxicillin-clavulanic acid, a second-generation cephalosporin, or a fluoroquinolone. Group 4 patients have frequent exacebations and tend to have a chronic progressive course. Many of these patients have underlying bronchiectasis. In addition to the foregoing listed pathogens, Enterobacteriaceae or Pseudomonas species may be isolated. A fluoroquinolone with activity against Pseudomonas is probably the best therapeutic choice. Ciprofloxacin is still the most active quinolone against P. aeruginosa.
There are many other aspects to the management of patients with chronic obstructive lung disease other than antibiotic therapy (10), which will not be discussed here. Seneff and colleagues (11) studied 362 patients with acute exacerbation of COPD who required admission to an intensive care unit (ICU). The in-hospital mortality was 24%. For the 165 patients who were 65 yr of age and older the in-hospital mortality rate was 30%; it was 41% at 90 d; 47% at 180 d, and 59% at 1 yr. Variables associated with in-hospital mortality (by multivariate analysis) included age, severity of respiratory and nonrespiratory organ dysfunction and hospital length of stay before ICU admission. Development of nonrespiratory organ dysfunction was the major predictor of hospital mortality—60% of the total explanatory power, and 180-day outcomes—54% of explanatory power. This study is in sharp contrast to the one by Torres and colleagues (12) in which 124 patients with chronic obstructive lung disease (COLD) and community-acquired pneumonia (CAP) who required admission to ICU had an 8% mortality.
The best treatment for chronic bronchitis is primary prevention—no smoking programs in schools and clean-air programs in communities would reduce the burden of COPD. Failing this primary preventive strategy, secondary prevention with yearly influenza vaccination and a single pneumococcal vaccine (repeated once in 6 years for select circumstances) does reduce the number of cases of pneumonia and hospital admissions.
2. PNEUMONIA 2.1. Clinical Relevance 2.1.1. Epidemiology
Pneumonia is a common and often serious illness. It is the sixth-leading cause of death in the United States. About 600,000 persons are hospitalized with pneumonia each year, and there are 64 million days of restricted activity due to this illness (13,14). Unmeasured to date is caregiver burden associated with pneumonia. Recovery is prolonged in the elderly (especially the frail elderly), and these patients may require up to 2 months to return to their baseline state of function.
The rate of pneumonia is highest at the extremes of age. In a population-based study in a Finnish town, Koivula and co-workers (15) found that 14/1000 persons/yr > 60
years of age developed pneumonia. Seventy-five percent of these cases of pneumonia were community acquired. In this study, independent risk factors for CAP were: alcoholism, relative risk (RR) 9; asthma, RR 4.2; immunosuppression, RR 1.9; age >70 vs. age 60-69 yr, RR 1.5.
For specific etiologies of pneumonia the risk factors may differ from those for pneumonia as a whole. Thus dementia, seizures, congestive heart failure, cerebrovascular disease and COLD were risk factors for pneumococcal pneumonia (16). Among human immunodeficiency virus-(HIV) infected patients the rate of pneumococcal pneumonia is 41.8 times higher than those in the same age group who are not HIV infected (17). Risk factors for Legionnaires' disease include male gender, tobacco smoking, diabetes mellitus, hematologic malignancy, cancer, end- stage renal disease, and HIV infection (18).
There have been major changes in both the host and microorganisms that are reflected in changes in the epidemiology of pneumonia. Penicillin-resistant S. pneumoniae (PRSP) is now a common in North American communities. Many of the PRSP isolates are resistant to three or more antibiotic classes (multidrug resistance). In a recent study, 14% of bacteremic S. pneumoniae isolates were resistant to penicillin, 12% to ceftazidime, and 24% were resistant to trimethoprim-sulfamethoxazole (19). In the study by Butler and colleagues (19), 740 S. pneumoniae isolates from sterile sites were collected during 1993-1994. Twenty-five percent of the isolates were resistant to more than one antibiotic; 3.5% were resistant to erythromycin, and 5% were resistant to clarithromycin (19). This is probably a harbinger for the future, in that in Madrid in 1992, 15.2% of S. pneumoniae isolates were resistant to erythromycin (20). Fortunately, it is possible to predict who is likely to have pneumonia due to PRSP. Previous use of ^-lactam antibiotics, alcoholism, non-invasive disease, age <5 or >65 yr and immunosuppression are risk factors for PRSP pneumonia (21,22). Host factors that have had a major impact on the epidemiology of pneumonia are increased in immunosuppressed individuals living in the community and are markedly increased in the advanced elder years (>80 years of age). Clustering of these individuals in retirement villages or nursing home has led to a new entity— nursing home-acquired pneumonia (NHAP).
There is a seasonal variation in the rate of pneumonia. Both attack rates and mortality rates are highest in the winter months (23). This is likely due to an interaction between influenzae viruses and S. pneumoniae. In a squirrel monkey model, infection with influenza A virus prior to S. pneumoniae inoculation led to a 75% mortality rate vs. no mortality for infection with influenzae virus alone (24).
Although there are well over 100 microbal agents that can cause pneumonia, only a few cause most of the cases of pneumonia. There are changes in the rank order of the causes of pneumonia according to the severity of illness (usually reflected in the site of care decision—home, hospital ward, hospital intensive care unit, or nursing home). Patients with CAP who are treated on an ambulatory basis are much younger than those who are treated in hospital. Mycoplasma pneumoniae is the most commonly identified etiological agent in this setting accounting for 24% of the cases (25-28). S. pneumoniae is probably underdiagnosed in outpatients, as a diagnostic workup is rarely done. In published data, S. pneumoniae account for about 5% of the cases of ambulatory pneumonia; in reality the number is probably closer to 50%. A compilation of data from 9 comprehensive studies of the etiology of CAP among 5225 patients requiring hospitalization identified S. pneumoniae as the etiological agent in 17.7% of cases (29-37). However, if one focuses on the 3 studies that used serological methods in addition to blood and sputum culture to identify S. pneumoniae, then this microorganism accounted for up to 50% of the cases of CAP (29,30,35). The etiology of NHAP is not well established since these studies have relied almost entirely on the results of sputum culture. The problem is distinguishing colonization from infection especially when aerobic Gram-negative bacilli such as Escherichia coli, Klebsiella spp., Proteus spp., Enterobacter spp., Pseudomonas aeruginosa, and so on are identified. Colonization of the oropharyngeal mucosa with aerobic Gram-negative bacilli increases with increasing age and is especially common among residents of nursing homes (38). S. pneumoniae is the most commonly identified agent in patients with nursing home-acquired pneumonia (NHAP). In 6 studies reporting on 471 patients with NHAP S. pneumoniae accounted for 12.9% of the cases, followed by H. influenzae, 6.4%; S. aureus, 6.4% M. catarrhalis, 4.4%; and aerobic Gram-negative bacilli, 13.1% (34,3943).
Pneumonia is an infection involving the alveoli and bronchioles. Pathologically it is characterized by increased weight and replacement of the normal lung sponginess by induration (consolidation). This induration may involve most or all of a lobe (or multiple lobes) or it may be patchy and localized around bronchi, i.e., bronchopneumonia. Microscopic examination can show dense alveolar infiltration with polymorphonuclear leukocytes as is found in patients with pneumonia due to bacterial agents or interstititial inflammation as is usually seen in viral pneumonia.
Clinically pneumonia is typically characterized by a variety of symptoms and signs. Cough that may produce purulent, mucopurulent, or "rusty" sputum is common; fever, chills, and pleuritic chest pain are other manifestations. Extrapulmonary symptoms such as nausea, vomiting, or diarrhea may occur. There is a spectrum of physical findings on chest examination, the most common of which is rales ("crackles") heard over the involved lung segment. Other findings that may be present include dullness to percussion, increased tactile and vocal fremitus, bronchial breathing, and a pleural friction rub. However, in many older patients, especially those who are frail and debilitated, typical respiratory manifestations may not be found. Such findings as cognitive impairment (delirium), decline in physical functional capacity, anorexia, weakness, or falls may be the initial or only symptoms or signs of pneumonia. Fever is often absent (44,45). A new opacity on chest radiographic examination is necessary to substantiate a clinical diagnosis of pneumonia.
The chance of determining a causative pathogen for pneumonia is approximately 60% in all age groups (46). The elderly have a lower diagnostic yield compared with younger patients with CAP (45% vs 70% in one study) (44). The inability to cough or provide quality sputum as well as oral and pharyngeal contamination of the specimen
Key Decisions in the Management of CAP
• Diagnostic workup
• Empiric antimicrobal therapy
• Switch from intravenous to oral antibiotic therapy
• Discharge decision
• Followup limit the usefulness of sputa as a diagnostic test for pneumonia in the elderly. Nevertheless, if quality sputa can be obtained, a Gram stain of the specimen can be examined to provide guidance on initial antimicrobal therapy. Blood culture (two sets) should be obtained in all elderly pneumonia patients who require hospitalization or intravenous therapy. Serological studies and tests for antigens in urine have been helpful in diagnosing certain types of pneumonia (e.g., Mycoplasma pneumoniae, Chlamydia spp., Legionella spp., viruses) (34). However, the information is obtained 3-4 weeks after initial clinical diagnosis. A chest roentgenograph and complete blood count, especially white blood cell count with differential count, should be obtained in every patient suspected of pneumonia (46).
Table 2 gives the key decisions that have to be made to successfully treat CAP. 2.4.1. Site of Care
The site of care is dictated by the severity of the pneumonia. This decision can be helped by using a severity of illness score. Fine and co-workers (47) developed a pneumonia specific severity of illness score. There are 20 different items (three demographic features, five comorbidity features, five physical examination findings, and seven laboratory data items). Points are assigned to each feature and summed. Patients are placed into one of five risk classes. Those in risk classes I-III are at low risk, <1% for mortality, whereas those in class IV had a 9% mortality, and class V patients had a 27% mortality rate. In general, patients in classes I-III could be treated at home whereas those in classes IV and V should hospitalized. The potential of this system is demonstrated by a study by Atlas and colleagues (48). These investigators prospectively enrolled 166 low-risk patients with pneumonia presenting to an emergency department. Physicians were given the pneumonia severity index score and offered enhanced visiting nursing services and the antibiotic clarithromycin. Two groups of controls were used—147 consecutive retrospective controls identified during the prior year and 208 patients from the study hospital who participated in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The percentage of patients initially treated as outpatients increased from 42% in the control period to 57% in the intervention period (36% relative increase; P =0.01). More outpatients failed outpatient therapy in the intervention period compared with the control period: 9% vs 0%, respectively. However, because these were historical controls, the conclusions from this study are weakened. Marrie and co-workers (49) enrolled 20 Canadian teaching and community hospitals into a study of a critical pathway for the management of CAP. Ten hospitals were randomized to the intervention arm (critical pathway) and 10 to conventional management. Hospitals were matched for teaching or community hospital status and for historic length of stay for patients with CAP. One teaching hospital in the intervention arm withdrew after randomization and was not replaced. Levofloxacin was the antibiotic used in the intervention arm, whereas antimicrobial therapy for patients in the conventional arm was at the discretion of the attending physician. The pneumonia-specific severity of illness score was used to assist with the site of care decision. An intent to treat analysis was performed on data from 1753 patients enrolled in the study. At the intervention hospitals the admission rate was lower for low-risk (classes I-III) patients, (31% vs 49% for conventional management; p = 0.013) or to use the terminology of Atlas and colleagues (48) 69% in the intervention arm were sent home vs. 41% in the conventional management arm. Follow-up of these patients revealed that there was no difference in the failure rates of outpatient therapy, i.e., about 6% of patients in both groups required admission.
2.4.2. Guidelines for Admission to Intensive Care Unit
The American Thoracic Society guidelines for the management of CAP gave criteria for severe pneumonia that could be used to help with the decision to admit a patient to an intensive care unit (ICU) (50). Ewig and co-workers (51) calculated the sensitivity, specificity, and positive and negative predict values of these criteria utilizing data from a prospective study of 422 consecutive patients with CAP, 64 of whom were admitted to an ICU. They found that no single criterion was of sufficient sensitivity to use alone. For example, a respiratory rate of >30 breaths per minute had a sensitivity of 64% and a specificity of 57%. Requirement for mechanical ventilation had a sensitivity of 58% and a specificity of 100%. Sensitivity and specificity values for other parameters were the following: septic shock, 38% and 100%; renal failure, 30% and 96%; systolic blood pressure <90 mmHg, 12% and 99%; diastolic blood pressure <60 mm Hg 15% and 95%; progressive pulmonary infiltrates, 28% and 92%; bilateral infiltrates, 41% and 86%; and multilobe infiltrates, 52% and 80%. Ewig and co-workers concluded that the definition of severe pneumonia using one of the American Thoracic Society criteria had a sensitivity of 32%, a specificity of 98%, a positive predictive value of 24%, and a negative predictive value of 99%. These authors developed new criteria for severe pneumonia, which include the three following parameters: arterial partial pressure of oxygen/inspired fraction of oxygen (Pa02/FI02) <250; multilobe infiltrates; and systolic blood pressure of 90 mmHg or less plus septic shock or mechanical ventilation. These three criteria together had a sensitivity of 78%, a specificity of 94%, and a positive predictive value of 75%.
The Infectious Diseases Society of America has published guidelines for the empiric therapy of CAP (52) (see Table 3). The recent introduction of fluoroquinolones with enhanced activity against S. pneumoniae and activity against most of the pathogens that cause CAP is an advance in the treatment of CAP. However, there are many unanswered questions regarding these new drugs: Which one is best? Should they be used only for patients requiring hospitalization? Will widespread use of the new fluoroquinolones for the treatment of ambulatory pneumonia
Antibiotic Therapy (First and Second Choices) of Community-Acquired Pneumonia When Etiology is Unknown (52)
A. Patient to be treated on an ambulatory basis
1. Macrolide (erythromycin 500 mg q 6h po x 10 d, clarithromycin 500 mg bid po x 10 days or azithromycin 500 mg po once then 250 mg/day po x 4 days)
2. Doxycycline 100 mg bid po x 10 days. If risk factors for penicillin or macrolide-resis-tant Streptococcus pneumoniae present, consider a fluoroquinolone with enhanced activity against S. pneumoniaea
1. Fluoroquinolone with enhanced activity against S. pneumoniae; e.g., levofloxacin, sparfloxacin, trovafloxacin or grepafloxacin6. (Levofloxacin 500 mg/d iv; trovafloxacin 200 mg/d iv; grepafloxacin6 600 mg/d po, sparfloxacin 400 mg x 1 dose then 200 mg/d po). If creatinine clearance <50 mL/min, reduce levofloxacin dose to 250 mg/d
2. Cefuroxime 750 mg q8h iv or ceftriaxone 1 g/d iv or cefotaxime 2 g q h iv plus azithromycin 500 mg/d.
1. Azithromycin 1 g iv then 500 mg/d iv plus ceftriaxone 1 g q 12 h iv or cefotaxime 2 g 8 h iv (ceftazidime and an aminoglycoside if Pseudomonas aeruginosa is suspected)
2. Fluoroquinolone with enhanced activity against S. pneumoniae (not recommended as first choice because of lack of clinical trial data in the ICU setting)
D. Patient to be treated in a nursing home
1. Amoxicillin - clavulanic acid 500 mg q 8 h po
2. Fluroquinolone with enhanced activity against S. pneumoniae
E. Aspiration pneumonia
1. Large-volume aspiration:Previous healthy individual—no antibiotic therapy
(a) Pneumonia (poor dental hygiene) and anaerobic infection suspected—clindamycin 2400-3600 mg/d iv in divided doses or penicillin 2-4 million units/d iv in divided doses
(b) Pneumonia in a nursing home or in elderly subject at home—amoxicillin-clavulinic acid plus fluoroquinolone
Abbreviations: bid, twice a day; po, oral; q, every; iv, intravenous; ICU, intensive care unit.
a Levofloxacin, sparfloxacin.
lead to the emergence of resistance among S. pneumoniae? The new fluoroquinolones are levofloxacin, sparfloxacin, moxifloxacin, grepafloxacin and trovafloxacin (trovafloxacin, at the time of this writing, has restricted indications because of reported cases of liver failure, and grepaflexacin has been removed from use because of prolonged QT interval resulting in torsade de pointes). There are others in the clinical trial stage (e.g., gatifloxacin). Some of the salient characteristics of these agents are summarized in Table 4. The advantages of the new fluoroquinolones are excellent bioavailability, so that even hospitalized non-ICU patients can be treated orally if they can eat and drink, and their activity against the spectrum of agents that cause CAP, hence only one antibiotic is necessary for the empiric treatment of CAP.
Salient Features of New Fluoroquinolones Compared With Ciprofloxacin
S. pneumoniae MICa
Penicillin sensitive (^g/mL) Penicillin resistant (^g/mL) P. aeruginosa MIC 90 (^g/mL) Percent bioavailability T \ (h)
Dosage adjustment Renal dysfunction Hepatic dysfunction Intravenous formulation available Usual oral dose to treat pneumonia C max (^g/mL) at dose given above AUC (mg x h/L)
Cipro Levo Grepa
70 99 72
Yes Yes No
No No Yes
Yes Yes No
500 mg bid 500 mg qd 600 mg qd
10 48 19.7
Gati Trova Moxi
approx 100% 88 90%
Yes No No
No Yes No
Yes Yes Yes
(alatrovafloxacin) (in development)
200 mg qd 200 mg qd 400 mg qd
a MIC = minimum inhibitory concentration; Cipro = ciprofloxacin; Levo = levofloxacin; Grepa = grepafloxacin; Gati = gatifloxacin; Trova = trovafloxacin; Moxi = moxifloxacin; qd = daily; bid = twice daily; T \ = drug half life; Cmax = peak serum or plasma concentration; AUC = area under the concentration vs time curve
In a series of studies, Ramirez and colleagues have defined criteria for switch from intravenous to oral antibiotics for treatment of patients with CAP (52,53). Criteria for switch to oral antibiotics include the following: (1) two normal temperature readings over 16 h in previously febrile patients, (2) white blood cell count returning toward normal, (3) subjective improvement in cough, and (4) subjective improvement in shortness of breath. Using these criteria 33 patients randomized to ceftizoxime therapy met switch criteria, in 2.76 d vs 3.17 d for those randomized to receive ceftriaxone (52). Seventy-four of the 75 evaluable patients were cured at 3-5 wk follow-up. Similar results were obtained in another study by this group in which patients were initially treated with ceftriaxone and, when criteria were met, patients were given clarithryomycin therapy orally. Ninety-six patients were enrolled in this study, and 59 were evaluable at 30-d follow-up. All 59 were cured (53). The presence of bacteremia or identification of high-risk pathogens such as S. aureus or P. aeruginosa are not contraindications for switch therapy (54). Patients who are clinically improving with empiric third-generation cephalosporin therapy are switched to oral third-generation cephalosporins, whereas patients who are receiving p-lactam/p-lactamase inhibitor agents are switched to oral p lactam/p-lactamase inhibitors. If intravenous therapy is with a P-lactam antbiotic and erythromycin, oral therapy is with a new macrolide (54).
Meehan and co-workers (55) carried out a retrospective multicenter cohort study of those >65 yr of age presenting to emergency rooms with CAP using Medicare National Claims History File from October 1, 1994 through September 30, 1995. Just over 75% of patients received antibiotics within 8 h of presenting at the emergency room. A significant lower 30-d mortality rate was observed for those who received antibiotic therapy within 8 h of presentation.
Halm and colleagues (56) defined how long it took to achieve stability in patients hospitalized with CAP. The median time to stability was 2 d for heart rate <100 beats/ min and systolic blood pressure > 90 mmHg. Three days were required to achieve stability if the following parameters were used: respiratory rate <24 breaths/min, oxygen saturation >90%, and temperature <37.2°C (<99°F). Once stability was achieved, clinical deterioration requiring admission to a critical care unit or telemetry monitoring occurred in less than 1% of patients. Patients in the study by Halm and co-workers frequently remained in hospital after reaching stability. In a recent study (Marrie and colleagues unpublished observations, 1999), it was found that immobility was a significant factor in prolonging hospital stay in the elderly with pneumonia.
All elderly patients with CAP should have a follow-up chest radiograph to verify that the pneumonia has resolved. Pneumonia distal to an obstructed bronchus is one of the presentations of cancer of the lung; in about 50% of these patients the diagnosis of cancer is made at the time of presentation. In the remainder, the main clue to the underlying disease is the failure of the pneumonia to resolve. Time to resolution of pneumonia is influenced by the patient's age and presence of underlying chronic obstructive pulmonary disease. The follow-up chest radiograph is best performed 10-12 wk after the diagnosis of pneumonia. If complete resolution has not occurred, further investigation to exclude an obstructed bronchus is necessary.
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