CITATION: Janoff EN, Rubins JB. 1996. Part 1: Clinical approach to community-acquired pneumonia: diagnosis and etiology. APUA Newsletter 14(3): 1-4,8...(Spanish version)

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Clinical approach to community-acquired pneumonia: diagnosis and etiology (Part 1)
Edward N Janoff, Jeffrey B Rubins
University of Minnesota School of Medicine, Minneapolis, Minnesota, USA

In an era of high-technology and evidence-based medicine, community-acquired pneumonia (CAP), the sixth leading cause of death,1 remains one of the most common, most serious and most studied, but least understood, clinical syndromes. Many primary care clinicians, as well as specialists, find the diagnosis difficult and rational and effective therapy elusive. This review of CAP will be presented in 2 parts: Part 1 discusses diagnosis and etiology and Part 2, to be published in the Winter 1996 issue, covers treatment and prevention.

Diagnosis of CAP
Clinical. The initial evaluation of a patient with a respiratory syndrome (eg, cough and shortness of breath) aims to distinguish pneumonia, an alveolar process, from proximal respiratory tract involvement (sinusitis, pharyngitis, bronchitis, reactive airways disease) (Fig. 1). Findings of temperature of greater than 37.8°C, pulse more than 100 beats/min, rales, decreased breath sounds and the absence of asthma predict an infiltrative lower respiratory tract process.2

Acute onset, fever, purulent sputum and an elevated leukocyte count in a patient older than 65 with underlying chronic medical conditions or cancer suggest infection. Non-infectious causes of pneumonia should be considered on initial evaluation, when patients do not respond appropriately to empiric therapy, in patients with a history of predisposing disease or use of medication (particularly methotrexate or amiodarone) or in those with evidence of extrapulmonary involvement, atypical radiographic findings and peripheral eosinophilia (Table 1). In addition, evidence of renal involvement, including renal dysfunction or positive urinary sediment, suggests a systemic inflammatory disease manifesting as pneumonitis.

Microbiology. The usefulness of a sputum Gram stain and culture may be limited as 25 to 50% of patients will not produce sputum or will have received prior antimicrobial therapy. The latter nullifies the results of stain and culture because Streptococcus pneumoniae and Haemophilus influenzae rarely grow in this situation, and only resistant but not necessarily causative organisms will be cultured. Nevertheless, a high-quality specimen, processed promptly, from a patient without prior therapy may help direct therapy.3 The Gram stain may also be useful to exclude pathogens such as Staphylococcus aureus and gram-negative bacilli, whose absence in an appropriately obtained quality specimen practically excludes their involvement in the process. AFB and KOH stains of sputum may identify mycobacterial and fungal but not viral pathogens.

Blood cultures are recommended for patients hospitalized with CAP, although only 10 to 15% will be positive and over half of these will yield S. pneumoniae.4,5 Positive results help limit the spectrum of antimicrobial therapy and assure the use of agents to which the organism is susceptible.

Serology. Serologic tests serve little purpose in the acute clinical setting. Increasing titers of antibody to Mycoplasma pneumoniae and Legionella species may suggest a diagnosis in retrospect but do not facilitate initial diagnosis and therapy. Serologic tests for fungi (eg, for coccidioidomycosis and histoplasmosis) may be useful for patients with persistent pneumonia. The most useful serologic test in adults aged 18 to 55 with CAP, particularly intravenous drug users and those with bacteremia, is for HIV.

Chest Radiography. The presence of a pneumonic process on radiography correlates with identifiable clinical signs as listed in Figure 1.2,6-8 Normal findings on a chest radiograph virtually exclude a diagnosis of pneumonia other than in HIV-infected patients with Pneumocystis carinii or, rarely, in dehydrated or neutropenic patients and those examined within 24 hours of the onset of symptoms. The pattern of infiltrate correlates less well with specific bacteriologic diagnoses. However, the combination of certain radiographic findings with associated clinical syndromes may direct the clinician to consider groups of organisms causing typical versus atypical pneumonia9 (see below).

Bronchoscopy. Fiberoptic bronchoscopy should be considered for severe or progressive cases of CAP, for potential opportunistic infections in immunocompromised patients and in patients with refractory pneumonitis suspected to be noninfectious. Even after prior administration of antibiotics, bronchoscopy may still reveal evidence of Legionella spp., anaerobic pneumonia and resistant or unusual pathogens, including tuberculosis, fungi and P. carinii. In addition, bronchoscopy can identify mechanical airway obstructions that may delay the resolution of pneumonia, including foreign bodies and endobronchial lesions. Bronchoalveolar lavage can be performed safely even in ventilated patients and has diagnostic yields of approximately 80%10; the use of protected catheter brushes may increase diagnostic yields slightly. Transbronchial biopsy is usually required to diagnose noninfectious pneumonitis and may facilitate diagnosis of infectious etiologies but adds risk of bleeding and pneumothorax.

Multiple studies and reviews have concluded that the most important and predictive clinical features that determine the response to therapy for CAP are the age and underlying health of the patient.4,5,11-13 Thus, our algorithm divides patients into those who are healthy and those with impaired health. More traditional but less well accepted of late are characterizations of clinical pneumonia syndromes as "atypical" or "typical."

Atypical pneumonia has a subacute onset, often with fever, malaise and headache. Sputum may be scant, chest radiography is patchy and effusion is not common. Leukocyte counts are usually less than 10,000/µL and a Gram stain of sputum shows no predominant organism. In contrast, typical pneumonia is lobar, more acute and more likely to produce purulent sputum, localized findings on chest radiography, consolidated infiltrates, elevated leukocyte counts and a diagnostic sputum Gram stain and culture or blood culture. These terms seem most useful early in the course of symptoms and evaluations.

Specific Causative Organisms
Streptococcus pneumoniae. The prototype of typical, or lobar, pneumonia, S. pneumoniae is consistently the leading cause of CAP in all adults (20 to 30% of cases; 2 cases per 1,000 adults per year). Cases occur with a distinct seasonal distribution from October to April. Symptoms develop acutely and resolve with therapy over several days. Mortality increases from less than 5% to more than 40% with age, underlying disease and the presence of bacteremia. Resistance to penicillin, although prevalent in many communities (identified in 5 to 25% of isolates), has not been shown to affect the clinical response to therapy. Bacteremic pneumococcal pneumonia is common among HIV-infected patients (approximately 1% per year). Doxycycline, macrolides, trimethoprim-sulfamethoxazole and cephalosporins are all reasonable therapies. Secondary foci (empyema, meningitis, arthritis) should be investigated in patients slow to respond. Although less common, group A beta-hemolytic streptococcus should be recognized as a cause of severe, acute, destructive pneumonia, often with pleural effusions and high mortality, and should be treated with penicillin.

Mycoplasma pneumoniae. The prototype for atypical pneumonia,9 these tiny organisms without cell walls may cause up to 20% of CAP, with no clear seasonal predominance. Occurring particularly among young adults, the onset may be insidious (7 to 14 days). A steady nonproductive cough is a prominent and persistent feature.14 Macrolides and doxycycline are standard therapy for M. pneumoniae and other organisms (particularly Chlamydia spp.) in this atypical pneumonia clinical group.

Haemophilus influenzae. This pleiomorphic gram-negative organism is among the most common causes of CAP, particularly in older adults, those who smoke and patients with underlying lung disease or immune dysfunction, particularly HIV infection.15,16 A syndrome of "febrile tracheobronchitis" with cough, purulent sputum and fever but no pulmonary infiltrate on chest radiography may be seen in older men with obstructive lung disease.17 Unlike with S. pneumoniae, bacteremia rarely accompanies H. influenzae pneumonia. ß-Lactamase-mediated ampicillin resistance is common (in more than 35% of cases), and because invasive H. influenzae disease in adults is often caused by nonencapsulated strains (50% of cases),18 current vaccines may be of limited value.

Moraxella catarrhalis. Although often found as an upper respiratory commensal organism, this gram-negative diplococcus may cause sinusitis and purulent tracheobronchitis as well as mild to moderate pneumonia in elderly patients with underlying lung disease.19 ß-Lactamase production requires the use of doxycycline, macrolides or second- or third-generation cephalosporins.

Chlamydia pneumoniae. Because of its relatively benign clinical course, C. pneumoniae, identified in 5 to 10% of cases of CAP,20,21 appears to be more common in patients treated as outpatients than in those hospitalized. Predictive diagnostic tests are not readily available. C. pneumoniae responds to treatment with 14 days of a macrolide or doxycycline but not sulfamides. However, symptoms, particularly cough, may persist for weeks. In contrast to M. pneumoniae, this intracellular organism is more common among older adults and infection may be preceded by pharyngitis and sinusitis.

Legionella pneumophila. This water-related pathogen causes 1 to 15% of CAP and should be suspected in outbreaks, among patients with cardiopulmonary disease and immune compromise and among those do not respond to ß-lactam antibiotics.22 The classic associated symptoms (gastrointestinal and neurologic), laboratory features (hyponatremia, abnormal liver function tests and hematuria) and the typical radiographic progression of focal alveolar infiltrates to dense multilobar consolidations are not specific for L. pneumophila infections. The diagnostic yield of a direct fluorescent antibody stain is up to 70%, whereas sputum cultures are insensitive (only about 10%). Urinary antigen testing is rapid, has an overall sensitivity of about 60% and remains positive for up to 1 year after infection. Patients typically respond promptly to a 3-week course of erythromycin (plus rifampin initially for the severely ill patient). Alternative therapies include doxycycline, clarithromycin, trimethoprim-sulfamethoxazole or fluoroquinolones.23,24

Influenza. Influenza infects up to one third of the US population per year and results in approximately 400,000 hospitalizations and 10,000 to 35,000 deaths, 80 to 90% of which are among patients older than 65.25 A clinical diagnosis of influenza is suggested by pneumonia accompanied by headaches and myalgias in the late fall or winter season, which may be complicated by secondary bacteria infection (eg, S. aureus and S. pneumoniae).26 For patients with influenza A, but not B, treatment with amantidine or rimantidine in the first 48 hours of symptoms reduces the duration of fever and illness. Other respiratory viruses (eg, adenovirus, parainfluenza virus and respiratory syncytial virus) are of importance primarily in severely immunocompromised hosts.

Mycobacterium tuberculosis. All patients in whom tuberculosis is suspected should be placed in isolation until 3 sputum specimens are confirmed by smear as negative for acid-fast bacilli. High-risk patients include immigrants, intravenous drug users, HIV-infected patients, the homeless, persons with lower socioeconomic status, institutionalized persons (from nursing homes, prisons) and those with a history of prior exposure (eg, in family).

Unusual causes of pneumonia. The pathogens typically associated with distinct geographic distributions or occupational and recreational exposures (Table 2) should be considered in patients immunocompromised because of chronic diseases or medications or who report recent travel or animal exposures associated with specific pathogens. In addition, several clinical findings on initial presentation, such as evidence of extrapulmonary involvement, gastrointestinal or neurologic symptoms, skin rashes and peripheral adenopathy, should raise the suspicion of unusual infectious pathogens. Atypical radiographic findings, including nodular infiltrates and prominent hilar or mediastinal adenopathy, and peripheral blood eosinophilia also suggest this possibility.

CAP of unknown etiology in adults. Despite the use of multiple microbiologic, serologic and molecular modalities, no pathogen can be implicated in 30 to 50% of cases of CAP. That mortality is high (13%) but no more so than with known pathogens suggests that current empiric therapy is adequate but not optimal. Advances in diagnostic techniques, rather than in antimicrobials, may improve these outcomes.20,27-30...Part 2-->

Acknowledgments
We thank Patti Kelly for her excellent secretarial assistance and the house staff of the University of Minnesota and Minneapolis VA Medical Center Internal Medicine residency program for thoughtful and practical comments.

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