Community-Acquired Pneumonia

Steven Schmitt

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Definition

Pneumonia is an infection of the lung parenchyma. Community-acquired pneumonia refers to pneumonia acquired outside of hospitals or extended-care facilities. Nursing home–acquired pneumonia refers to infection acquired in an extended-care facility. Nosocomial pneumonia and hospital-acquired pneumonia describe infections acquired in the hospital setting. The signs and symptoms of acute pneumonia develop over hours to days, whereas the clinical presentation of chronic pneumonia often evolves over weeks to months.

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Prevalence

Despite a broad armamentarium of antimicrobials available to treat the disease, pneumonia remains the seventh leading cause of death in the United States.1 In 2003, the age-adjusted death rate caused by influenza and pneumonia was 20.3 per 100,000 persons.1 Estimates of the incidence of community-acquired pneumonia range from 4 million to 5 million cases per year, with about 25% requiring hospitalization.2 Nosocomial pneumonia is estimated to occur in 250,000 persons per year, representing about 15% to 18% of all nosocomial infections.3,4

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Microbiology

Streptococcus pneumoniae remains the most commonly identified pathogen in community-acquired pneumonia (Fig. 1). Other pathogens have been reported to cause pneumonia in the community, and their order of importance depends on the location and population studied (Table 1). These include long-recognized pathogens such as Haemophilus influenzae, Mycoplasma pneumoniae, and influenza A, along with newer pathogens such as Legionella species and Chlamydophilia pneumoniae. Other common causes in the immunocompetent patient include Moraxella catarrhalis, Mycobacterium tuberculosis, and aspiration pneumonia. The causative agent of community-acquired pneumonia remains unidentified in 30% to 50% of cases.5

Table 1: Identified Pathogens in Community-Acquired Pneumonia
Pathogen Cases (%)
Streptococcus pneumoniae 20-60
Haemophilus influenzae 3-10
Staphylococcus aureus 3-5
Gram-negative bacilli 3-10
Legionella species 2-8
Mycoplasma pneumoniae 1-6
Chlamydia pneumoniae 4-6
Viruses 2-15
Aspiration 6-10
Others 3-5

Adapted from Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-1433.
© 2002 The Cleveland Clinic Foundation.

Previously seen mainly in extended-care facilities and acute-care hospitals, strains of methicillin-resistant Staphylococcus aureus (MRSA) have emerged as prevalent pathogens in community settings.6 Necrotizing pneumonia is a characteristically severe manifestation of these virulent strains.

A new human pathogen, severe acute respiratory syndrome (SARS)-associated coronavirus, emerged and spread worldwide in the winter of 2002 to 2003. No cases have been identified since 2004. Data regarding this virus and its associated syndrome, SARS,7 can be found on the SARS page of the website of the Centers for Disease Control and Prevention (CDC), available at http://www.cdc.gov/ncidod/sars.

Influenza continues to be a prevalent seasonal disease in the United States, causing considerable morbidity, loss of productivity, and mortality. A strain of H5N1 influenza has spread rapidly through avian flocks in Asia and Europe. Cases of transmission from birds to humans with severe disease have led to international concern about a possible avian influenza pandemic. Readers are encouraged to check the CDC influenza page, available at http://www.cdc.gov/flu/avian/index.htm, for updated prevention and treatment guidelines, as well as the latest epidemiologic information. Other viral causes of respiratory tract infections include parainfluenza virus, adenovirus, human metapneumovirus, herpes zoster virus (HSV), varicella-zoster virus (VZV), and measles.

Many pathogens listed as potential agents of bioterrorism are spread by the respiratory route. Among the most likely candidates are Bacillus anthracis, Francisella tularensis, and Yersinia pestis. A more extensive discussion of the agents of bioterrorism can be found elsewhere in this section (“Biologic Weapons and the Primary Care Clinician”).

Nursing home–acquired pneumonias are often caused by community-acquired pathogens. However, there is an increased influence of pathogens seen with relatively low frequency in the community, such as S. aureus and gram-negative organisms.

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Pathophysiology

Six mechanisms have been identified in the pathogenesis of pneumonia in immunocompetent adults (Table 2). Inhalation of infectious particles is probably the most important pathogenetic mechanism in the development of community-acquired pneumonia, with particular importance of pneumonia caused by Legionella species and M. tuberculosis.

Table 2: Pathogenetic Mechanisms in Pneumonia
Mechanism Frequency
Inhalation of infectious particles Common
Aspiration of oropharyngeal or gastric contents Common
Hematogenous deposition Uncommon
Invasion from infection in contiguous structures Rare
Direct inoculation Less common
Reactivation More common in immunocompromised hosts

© 2002 The Cleveland Clinic Foundation.

The aspiration of oropharyngeal or gastric contents is the most prevalent pathogenetic mechanism in nosocomial pneumonia, with several contributing factors. Swallowing and epiglottic closure may be impaired by neuromuscular disease, stroke, states of altered consciousness, or seizures. Endotracheal and nasogastric tubes interfere with these anatomic defenses and provide a direct route of entry for pathogens. Impaired lower esophageal sphincter function and nasogastric and gastrostomy tubes increase the risk of aspiration of gastric contents. Fortunately, aspiration rarely leads to overt bacterial pneumonia.

Direct inoculation rarely occurs as a result of surgery or bronchoscopy but may play a role in the development of pneumonia in patients supported with mechanical ventilation. Hematogenous deposition of bacteria in the lungs is also uncommon but is responsible for some cases of pneumonia caused by S. aureus, Pseudomonas aeruginosa, and Escherichia coli. The direct extension of infection to the lung from contiguous areas, such as the pleural or subdiaphragmatic spaces, is rare.

Reactivation of pathogens can take place in the setting of deficits of cell-mediated immunity. Pathogens such as Pneumocystis jiroveci, Mycobacterium tuberculosis, and cytomegalovirus can remain latent for many years after exposure, with flares of active disease occurring in the presence of immune compromise. Reactivation tuberculosis occasionally occurs in immunocompetent hosts.

Once bacteria reach the tracheobronchial tree, defects in local pulmonary defenses can make infection more likely. The cough reflex can be impaired by stroke, neuromuscular disease, sedatives, or poor nutrition. Mucociliary transport is depressed with the aging process, tobacco smoking, dehydration, morphine, atropine, prior infection with influenza virus, and chronic bronchitis. Anatomic changes such as emphysema, bronchiectasis, and obstructive mass lesions prevent the clearance of microbes. Inflammatory cells drawn to infected areas of the pulmonary tree release proteolytic enzymes, altering the bronchial epithelium and ciliary clearance mechanisms and stimulating the production of excess mucus. Community-acquired MRSA strains contain Panton-Valentine leukocidin, a toxin that creates holes in neutrophil cell membranes, releasing chemotactic and inflammatory factors.7

A blunted cellular and humoral immune response can also increase the risk of pneumonia. For example, granulocyte chemotaxis is reduced with aging, diabetes mellitus, malnutrition, hypothermia, hypophosphatemia, and corticosteroids. Granulocytopenia may be caused by cytotoxic chemotherapy. Alveolar macrophages are rendered dysfunctional by corticosteroids, cytokines, viral illnesses, and malnutrition. Diminished antibody production or function can accompany hematologic malignancies such as multiple myeloma or chronic lymphocytic leukemia.

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History and physical examination

Because the clinical syndromes characterizing pneumonic infections caused by various agents often overlap one another and because interobserver variability regarding physical findings of pneumonia is high, the diagnosis of pneumonia can be challenging. A diligent history (Table 3) and physical examination can help narrow the differential diagnosis. In general, typical bacterial pathogens such as S. pneumoniae, H. influenzae, and the enteric gram-negative organisms usually manifest acutely with high fever, chills, tachypnea, tachycardia, and productive cough. Examination findings are localized to a specific lung zone and can include rales, rhonchi, bronchial breath sounds, dullness, increased fremitus, and egophony. In contrast, atypical pathogens such as Mycoplasma, Chlamydophilia, and viruses can manifest in a subacute fashion with fever, nonproductive cough, constitutional symptoms, and absent or diffuse findings on lung examination. Rapid progression of disease to respiratory failure can be seen in severe pneumococcal or Legionella pneumonia. Influenza may be complicated by bacterial pneumonia caused by S. aureus or S. pneumoniae.

Table 3: Microbiologic Differential Diagnosis of Pneumonia: Historical Features
History Associated Organisms
Alcoholism Streptococcus pneumoniae, oral anaerobes, Mycobacterium tuberculosis
Chronic obstructive lung disease (COPD) S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella spp.
Exposure to bat or bird droppings, construction sites, caves Histoplasma capsulatum
Exposure to birds Chlamydia psittaci
Exposure to rabbits Francisella tularensis
HIV infection “Typical” bacterial pathogens, M. tuberculosis, Pneumocystis jiroveci, cytomegalovirus, Cryptococcus spp., Histoplasma spp., Coccidioides spp.
Travel to desert, southwest United States Coccidioides spp., Hantavirus (Sin Nombre virus)
Farm exposure Coxiella burnetii (animals), Aspergillus spp. (barns, hay)
Postinfluenza S. pneumoniae, S. aureus, Streptococcus pyogenes, H. influenzae
Aspiration Mixed aerobic, anaerobic
Marijuana smoking Aspergillus spp.
Anatomic abnormality of lung parenchyma, e.g., bronchiectasis, cystic fibrosis Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus
Injection drug use S. aureus, anaerobes, M. tuberculosis, and S. pneumoniae
Obstruction of large airway Anaerobes, S. pneumoniae, H. influenzae, S. aureus
Incarceration M. tuberculosis
Neutropenia Aspergillus spp., Zygomycetes
Asplenia S. pneumoniae, H. influenzae

Adapted from Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-1433.
© 2002 The Cleveland Clinic Foundation.

SARS manifests with high fever and myalgia for 3 to 7 days, followed by a nonproductive cough and progressive hypoxemia, with progression to mechanical ventilation in 20% of cases. This can be distinguished from other viral infections by the higher fever and lack of conjunctivitis, sneezing, rhinorrhea, and pharyngitis. Inhalation anthrax can manifest with flulike symptoms of myalgia, fatigue, and fever before rapidly progressing to respiratory distress, mediastinitis, meningitis, sepsis, and death.

The age of the patient can play an important role in disease presentation. Older patients often have humoral and cellular immunodeficiencies as a result of underlying diseases, immunosuppressive medications, and the aging process. They are more commonly institutionalized with anatomic problems that inhibit the pulmonary clearance of pathogens. The presentation is often more subtle than in younger adults, with more-advanced disease and sepsis, despite minimal fever and sputum production.

Extrapulmonary physical findings can provide clues to the diagnosis. Poor dentition and foul-smelling sputum can indicate the presence of a lung abscess with an anaerobic component. Bullous myringitis can accompany infection with M. pneumoniae. An absent gag reflex or altered sensorium raises the question of aspiration. Encephalitis can complicate pneumonia caused by M. pneumoniae or Legionella pneumophila. Cutaneous manifestations of infection can include erythema multiforme (M. pneumoniae), erythema nodosum (C. pneumoniae and M. tuberculosis), or ecthyma gangrenosum (P. aeruginosa).

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Diagnostic and treatment considerations

The composition of the diagnostic workup for pneumonia has been the subject of some disagreement among experts (see later, “National Guidelines”), but a well-chosen evaluation can support a diagnosis of pneumonia and identify a pathogen.

Radiography

A cornerstone of diagnosis is the chest x-ray, which is recommended for diagnosis in every circumstance and usually reveals an infiltrate (Fig. 2) at presentation. However, this finding may be absent in the dehydrated patient. Also, the radiographic manifestations of chronic diseases such as congestive heart failure, chronic obstructive pulmonary disease (COPD), and malignancy can obscure the infiltrate of pneumonia.

Although radiographic patterns are usually nonspecific, they can suggest a microbiologic differential diagnosis (Table 4).

Table 4: Radiographic Patterns of Common Etiologic Agents
Chest Radiographic Pattern Pathogen
Focal; large pleural effusion Usually bacteria
Cavitary Bacterial abscess, fungi, acid-fast bacilli, Nocardia
Miliary Acid-fast bacilli, fungi
Rapid progression/multifocal Legionella spp., Pneumococcus, Staphylococcus
Interstitial Viruses, Pneumocystis jiroveci, Mycoplasma, Chlamydia psittaci
Mediastinal widening without infiltrate Inhalation anthrax

© 2002 The Cleveland Clinic Foundation.

Initial Management: Risk Stratification and Treatment Setting

When community-acquired pneumonia is strongly suspected on the basis of history, physical examination, and chest radiography, the next critical management decision is whether the patient requires hospital admission. Health care budgetary constraints have given rise to a number of studies addressing the need for hospitalization in community-acquired pneumonia. A study by the Patient Outcome Research Team (PORT) investigators has validated a risk scale, now called the pneumonia severity index (PSI), for mortality in community-acquired pneumonia. Point values are assigned to patient characteristics, comorbid illness, physical examination, and basic laboratory findings (Table 5).8 Patients younger than 50 years without comorbid illness or significant vital sign abnormalities (risk class I) were found to have a low risk for mortality. The authors suggested that such patients might be eligible for outpatient antibiotic therapy without extensive laboratory evaluation.

Table 5: Pneumonia Severity Index: Point Assignments in Community-Acquired Pneumonia
Risk Factor Point Value
Age
Men Age (in yr)
Women Age (in yr) −10
Nursing home resident +10
Comorbid Illnesses
Neoplastic disease +30
Liver disease +20
Kidney disease +10
Cerebrovascular disease +10
Congestive heart failure +10
Physical Findings
Altered mentation +20
Tachypnea (>30 breaths/min) +20
Systolic hypotension (<90 mm Hg) +20
Body temperature (<35° or >40° C) +15
Heart rate >125 beats/min +10
Laboratory and Radiographic Findings
Blood pH (arterial) <7.35 +30
Hypoxemia (arterial Pao2<60 mm Hg or O2 saturation <90%) +10
Serum urea nitrogen (BUN) >30 mg/dL +20
Na <130 mEq/L +20
Blood sugar >250 mg/dL +10
Anemia (hematocrit <30%) +10
Pleural effusion 10

Adapted from Kolleff MH, Micek ST: Methicillin-resistant Staphylococcus aureus—a new community-acquired pathogen? Curr Opin Infect Dis 2006;19:161-168.
© 2002 The Cleveland Clinic Foundation.

All others were evaluated with the laboratory tests listed in Table 5 and assigned to risk classes by point totals (Table 6). Those in classes I and II are considered excellent candidates for outpatient oral therapy, assuming no hemodynamic instability, no chronic oxygen dependence, immunocompetence, and the ability to ingest, absorb, and adhere to an oral regimen. Patients in risk class III may be considered for outpatient or brief inpatient therapy, depending on clinical judgment. Patients in risk classes IV and V are recommended for hospital admission. Ultimately, each decision to admit must be individualized.

Table 6: Pneumonia Severity Index: Risk of 30-Day Mortality By Point Total
Risk Class Point Score Mortality (%)
I No points assigned 0.1
II <70 0.6
III 71-90 2.8
IV 91-130 8.2
V >130 29.2

Adapted from Kolleff MH, Micek ST: Methicillin-resistant Staphylococcus aureus—a new community-acquired pathogen? Curr Opin Infect Dis 2006;19:161-168.
© 2002 The Cleveland Clinic Foundation.

A slightly less complex scheme is the CRB-65. In this algorithm, patients are felt better served by hospitalization if they they meet more than of the following criteria: confusion, respiratory rate greater than 30 breaths per minute, blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic, or age older than 65 years.9

Diagnostic Testing

When the patient is not severely ill (ie outpatient treatment or not severely ill in the inpatient setting) and has few risk factors, the consensus guidelines of the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS)10 suggest empirical therapy without extensive laboratory evaluation (Box 1). When identification of a pathogen might change therapy, further studies are indicated (see Box 1). The value of such studies is not uniformly agreed on (see later, “National Guidelines”). However, pathogen identification has important implications for the breadth of therapeutic antibiotic spectrum, development of resistance, and epidemiology.

Box 1: Diagnostic Testing for Community-Acquired Pneumonia
All patients with suspected pneumonia
  • Chest radiography
  • Complete blood count
  • Complete metabolic profile
  • Blood gases or pulse oximetry
Severely ill or immunocompromised patients, patients with anatomic lung disease
  • Sputum Gram stain and culture
  • Blood cultures: two sets before antibiotics
  • Legionella serology, urinary antigen, direct fluorescent antibody testing
  • Pneumococcal urinary antigen testing
Inpatients with appropriate history or physical findings
  • HIV serology
  • Mycoplasma serology
  • Chlamydia serology
  • Fungal serology
  • SARS-associated coronavirus serology or PCR
  • Stains or cultures for fungi, mycobacteria, Pneumocystis jiroveci
  • Analysis or cultures of pleural or cerebrospinal fluid
  • Nasopharyngeal swab for viral direct fluorescent antibody or other rapid technique
  • Tuberculin skin testing
Deteriorating patient without definitive diagnosis of cause
  • Bronchoscopy (bronchoalveolar lavage, protected catheter, transbronchial biopsy)
  • Thoracoscopic or open-lung biopsy
  • Radiographically guided transthoracic aspirate
  • Legionella, Chlamydia, Mycoplasma serology
  • Fungal serology
  • Evaluation for congestive heart failure, pulmonary embolus, neoplasm, connective tissue disease

PCR, polymerase chain reaction; PORT, Patient Outcome Research Team; SARS, severe acute respiratory syndrome.
Adapted Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72.
© 2004 The Cleveland Clinic Foundation.


A Gram-stained sputum specimen can help focus empirical therapy. Unfortunately, sputum is often difficult to obtain from older patients because of a weak cough, obtundation, and dehydration. Nebulized saline treatments might help mobilize secretions. Nasotracheal suctioning can sample the lower respiratory tract directly but risks oropharyngeal contamination. A sputum specimen reflects lower respiratory secretions when more than 25 white blood cells (WBCs) and fewer than 10 epithelial cells are seen in a low-powered microscopic field.11 Empirical therapy based on a predominant organism in such a specimen is likely to contain appropriate coverage.12

Other stains, such as the acid-fast stain for mycobacteria, modified acid-fast stain for Nocardia, or toluidine blue and Gomori's methenamine silver stains should be used when directed by the history or clinical presentation. Direct fluorescent antibody (DFA) staining of sputum, bronchoalveolar lavage fluid, or pleural fluid can help identify Legionella species. Similarly, DFA testing of nasopharyngeal specimens provides rapid diagnosis of influenza types A and B, as well as other common respiratory viruses such as respiratory syncytial virus, adenovirus, and parainfluenza virus. In an outbreak setting, DFA and other rapid techniques can assist in decision making for therapy and infection control.

The sputum culture remains a controversial tool but is useful to help tailor therapy when the patient is severely ill, has a history of structural lung disease or alcohol abuse, has pleural effusion, or has evidence of pneumococcal or Legionella infection. Culture is particularly helpful for identifying organisms of epidemiologic significance, either for patterns of transmission or resistance. Expectorated morning sputum specimens should be sent for mycobacterial culture when the history is suggestive.

Blood cultures can also shed light on a pathogen, and samples should be drawn in severely ill or immunocompromised patients (see later, “Outcomes”). Pleural or cerebrospinal fluid should be sampled when infections in these spaces are suspected.

When these procedures fail to yield a microbiologic diagnosis and when the patient does not respond to empirical antibiotic therapy, more-invasive diagnostic techniques may be indicated. Fiberoptic bronchoscopy allows the use of several techniques for the diagnosis of pneumonia. Bronchoalveolar lavage with saline can obtain deep respiratory specimens for the gamut of stains and cultures mentioned earlier. Transbronchial biopsy of lung parenchyma can reveal alveolar or interstitial pneumonitis, viral inclusion bodies, and fungal or mycobacterial elements. The protected brush catheter is used to distinguish quantitatively between tracheobronchial colonizers and pneumonic pathogens.

A more substantial amount of lung tissue may be obtained for culture and histologic examination by thoracoscopic or open lung biopsy. Because these procedures can carry considerable morbidity, they are usually reserved for the deteriorating patient with a pneumonia that defies diagnosis by less-invasive techniques.

Serologic Testing

Often relegated to retrospective or epidemiologic interest because of delays in testing or reporting, serologic testing for such pathogens as Legionella species, Mycoplasma species, and C. pneumoniae should include sera drawn in the acute and convalescent phases for comparison. A fourfold increase in the immunoglobulin G (IgG) titer suggests recent infection with these organisms. An IgM microimmunofluorescence titer of more than 1:16 is considered diagnostic of C. pneumoniae infection. Infection with SARS-associated coronavirus is most often diagnosed by antibody testing and polymerase chain reaction (PCR) testing.

A sensitive enzyme immunoassay has been developed for the detection of L. pneumophila type 1 antigen in urine. Because the antigen persists for up to 1 year after infection, it is difficult to differentiate between past and current infections when using this assay.

A urinary assay is also available for detecting S. pneumoniae cell wall polysaccharide. This assay may offer some advantage for the rapid diagnosis of pneumococcal pneumonia in culture-proven or unknown cases, but assay specificity is an ongoing question.

Molecular Techniques

Powerful molecular techniques are now being applied to the early diagnosis of pneumonia. DNA probes have been used to detect Legionella species, M. pneumoniae, and M. tuberculosis in sputum. These probes have excellent sensitivity and specificity but can yield false-positive results. The PCR assay has been used for the early detection of various pathogens that are difficult or slow to culture from sputum specimens, including atypical bacteria, viruses (e.g., influenza), and mycobacteria. Given the large percentage of pneumonia cases for which no microbial cause is identified, it is likely that molecular tools will eventually be applied to the identification and antimicrobial susceptibility testing of almost all causative agents of pneumonia.

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Summary

  • The patient's history can help narrow the microbial differential diagnosis.
  • The chest radiograph is the cornerstone of diagnosis.
  • The sputum Gram stain and culture are controversial, but they are still useful for targeting antimicrobial therapy when the patient is severely ill or immunocompromised.
  • Serologic testing is slow and therefore often not useful for real-time diagnosis.
  • Molecular methods are playing an increasing role in identifying difficult-to-culture pathogens.
  • The pneumonia severity index uses history, examination, chest radiograph, and initial laboratory test results to identify low-risk patients for outpatient treatment.

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Antimicrobial treatment

Community-Acquired Pneumonia

Antibiotic therapy for community-acquired pneumonia should always be selected with patient characteristics, place of acquisition, and severity of disease in mind. With concerns about antimicrobial overuse, health care costs, and bacterial resistance increasing, many experts believe that therapy should always follow confirmation of the diagnosis of pneumonia and should always be accompanied by a diligent effort to identify a causative agent (see later, “National Guidelines”). When a specific pathogen is identified, pathogen-specific therapy can be used (Table 7).

Table 7: Pathogen-Specific Therapy for Community-Acquired Pneumonia in Adults
Organism Primary Therapy
Streptococcus pneumoniae, penicillin-susceptible Penicillin G; amoxicillin
S. pneumoniae, penicillin-resistant Cefotaxime, ceftriaxone, fluoroquinolone, vancomycin, others, based on susceptibility studies
Haemophilus influenzae Second- or third-generation cephalosporin, doxycycline, beta-lactam or beta-lactamase inhibitor, azithromycin, TMP-SMX
Moraxella catarrhalis Second- or third-generation cephalosporin, TMP-SMX macrolide, beta-lactam or beta-lactamase inhibitor
Legionella spp. Macrolide, tetracycline, fluoroquinolone alone
Mycoplasma pneumoniae Doxycycline, macrolide
Chlamydia pneumoniae Doxycycline, macrolide
Anaerobes Beta-lactam or beta-lactamase inhibitor, clindamycin
Enteric gram-negative bacilli Third-generation cephalosporin ± aminoglycoside; carbapenem
Pseudomonas aeruginosa Aminoglycoside + ticarcillin, piperacillin, mezlocillin, ceftazidime, cefepime, aztreonam, or carbapenem
Staphylococcus aureus, methicillin-susceptible Nafcillin or oxacillin
S. aureus, methicillin-resistant Vancomycin or linezolid
Bacillus anthracis Ciprofloxacin or doxycycline + two of the following: rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, clarithromycin
Influenza A, within 48 hr of symptom onset or immunocompromised host Amantidine, rimantadine, oseltamivir, zanamivir
Influenza B, within 48 hr of symptom onset or immunocompromised host Oseltamivir, zanamivir

*For community-acquired methicillin-resistant S. aureus, some clinicians add agents that inhibit toxin production, such as clindamycin, when susceptibility patterns allow.
TMP-SMX, trimethoprim-sulfamethoxazole.
Adapted from Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72.
© 2003 The Cleveland Clinic Foundation.

When a pathogen is yet to be identified, empirical therapy is instituted. A number of expert panels have recommended empirical pneumonia therapy, most prominently IDSA and ATS (Table 8).

Table 8: Empirical Antimicrobial Therapy for Community-Acquired Pneumonia In Immunocompetent Adults
Patient, Setting Common Pathogens Empirical Therapy
Outpatients
<60 yr
No comorbid diseases
Streptococcus pneumoniae
Mycoplasma pneumoniae
Chlamydia pneumoniae
Haemophilus influenzae
Viruses
Macrolide or doxycycline
>65 yr or with comorbid disease or antibiotic therapy within last 3 mo S. pneumoniae (drug-resistant)
M. pneumoniae
C. pneumoniae
H. influenzae
Viruses
Gram-negative bacilli
S. aureus
Macrolide or doxycycline fluoroquinolone*
Beta-lactam and macrolide
Inpatients
Not severely ill S. pneumoniae
H. influenzae
Polymicrobial
Anaerobes
S. aureus
C. pneumoniae Viruses
Macrolide and cefotaxime or ceftriaxone, or beta-lactam or beta-lactamase inhibitor; fluoroquinolone alone
Severely ill S. pneumoniae §
Legionella spp.
Gram-negative bacilli
M. pneumoniae
Viruses
S. aureus
Azithromycin, or fluoroquinolone and cefotaxime, ceftriaxone, or beta-lactam or beta-lactamase inhibitor
If P. aeruginosa possible—IV macrolide or fluoroquinolone and aminoglycoside IV, or antipseudomonal quinolone and antipseudomonal beta-lactam
If MRSA possible, add vancomycin or linezolid

*In the outpatient setting, many authorities prefer to reserve fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) for patients with comorbid diseases or risk factors.
In most cases, patients with pneumonias caused by these organisms should be hospitalized.
Levofloxacin, gatifloxacin, moxifloxacin.
§Critically ill patients in areas with significant rates of high-level pneumococcal resistance and a suggestive sputum Gram stain should receive vancomycin or a newer quinolone pending microbiologic diagnosis.
Piperacillin-tazobactam or ampicillin-sulbactam.
¶Cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin-clavulanate, or parenteral ceftriaxone followed by oral cefpodoxime. **Cefotaxime, ceftriaxone, ampicillin-sulbactam, or high-dose ampicillin Adapted from Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-S72. © 2003 The Cleveland Clinic Foundation.

Aspiration Pneumonia

Clindamycin is preferred over penicillin for the treatment of community-acquired aspiration pneumonia because of its superiority for treating oral anaerobes such as Bacteroides melaninogenicus. Amoxicillin-clavulanic acid also provides excellent coverage in this setting. When large-volume aspiration is documented in the hospital, a beta-lactam–beta-lactamase inhibitor combination or the combination of clindamycin and an antipseudomonal agent should be used.

Other Considerations

Anthrax

Suspected or proven inhalation anthrax should be treated with ciprofloxacin or doxycycline and two other agents (see Table 7). Clinical experience has suggested that rifampin may be an important agent in empirical regimens.13

Duration of Therapy

Although few data specifically address the duration of therapy, many cases of pneumonia are adequately treated with 10 to 14 days of antibiotics. Longer courses may be required for certain organisms that cause tissue necrosis, (e.g., Legionella spp., S. aureus, Pseudomonas aeruginosa), organisms that live intracellularly (e.g., C. pneumoniae), or comorbidities that compromise local (COPD) or systemic (hematologic malignancy) immunity.

Oral and Switch Therapies

The use of oral or switch therapies offers potential reductions in duration of stay, antibiotic administration costs, complications of venous access, and disruption of families and careers. Many antibiotics are well absorbed from the gastrointestinal tract, suggesting the possibility of effective fully oral treatment. Because well-controlled, risk-stratified data comparing oral and intravenous therapies are few, appropriate patient populations and treatment settings for full-course oral therapy have yet to be fully defined. Better data exist for the use of IV to oral switch therapies for the stable patient who has good gastrointestinal and swallowing function and adequate social support.14

Failure to Respond to Initial Therapy

Worsening of clinical status despite adequate antibiotic therapy should trigger a reassessment of the original clinical impression. First, the diagnosis of infection must be questioned. Entities such as cancers, pulmonary edema, pulmonary embolus, pulmonary hemorrhage, connective tissue diseases, or drug toxicity can mimic the clinical and radiographic appearance of pneumonia. Organisms with inherent (e.g., fungi, mycobacterial, P. jiroveci) or acquired (Pseudomonas aeruginosa) resistance to drugs commonly used in pneumonia therapy must also be considered. A secondary infection, such as postinfluenza staphylococcal pneumonia, might prove resistant to initial therapy. The patient might fail to respond for reasons of poor adherence, poor drug absorption, or drug interaction. Finally, immunodeficiency (e.g., HIV, hematologic malignancy) or anatomic derangement (e.g., COPD, bronchiectasis, neoplasm) can alter the clinical course of pneumonia and treatment.

Discharge Criteria

Criteria for hospital discharge in community-acquired pneumonia are based on common sense. Candidates for discharge should have no more than one of the following poor prognostic indicators: temperature higher than 37.8° C, pulse higher than 100 beats/min, respiratory rate higher than 24/min, systolic blood pressure lower than 90 mm Hg, oxygen saturation lower than 90%, and inability to maintain oral intake.

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Summary

  • Antibiotic therapy for community-acquired pneumonia should always be selected with patient characteristics, place of acquisition, severity of disease, and local resistance patterns in mind.
  • Antimicrobial therapy should be narrowed whenever a pathogen is identified.
  • Most pneumonias, with some exceptions, can be cured with 10 to 14 days of antibiotic therapy.
  • Switching to oral therapy is possible and desirable once the patient stabilizes.
  • Failure to respond to initial therapy should raise questions of diagnosis, treatment adherence, and antimicrobial resistance.

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Prevention

Immunization against influenza and increasingly resistant pneumococci can play a critical role in preventing pneumonia, particularly in immunocompromised and older adults. The influenza vaccine is formulated and administered annually. The Centers for Disease Control and Prevention (CDC) recommends that vaccines be offered to persons older than 50 years, residents of extended-care facilities, and patients who have chronic heart and lung disorders, chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression.15

The pneumococcal vaccine has been shown to be 60% to 70% effective in immunocompetent patients. Side effects are rarely serious and consist of local pain and erythema, which occur in up to 50% of recipients. The CDC recommends that vaccines be offered to all persons 65 years of age or older, those at increased risk for illness and death from pneumococcal disease because of chronic illness, those with functional or anatomic asplenia, and immunocompromised persons.16 Patients who are immunosuppressed by chronic disease or treatment might not have sustained titers of protective antibody and should be considered for revaccination after 6 years.

Residual immunity against Bordetella pertussis wanes over time, leading to transmission from older adults to other adults and infants. Because secondary bacterial pneumonia occurs in a significant number of cases of pertussis, the ACIP (Advisory Committee on Immunization Practices) has recommended that the tetanus-diphtheria-acellular pertussis (Tdap) vaccine replace the tetanus-diphtheria (Td) vaccine in the adult immunization schedule.17

The emergence of SARS, with significant spread in hospitals, forced an extensive reassessment of respiratory infection control in many institutions. Measures to prevent the spread of SARS-associated coronavirus include close attention to cough hygiene, hand hygiene, contact precautions, and respiratory droplet precautions.

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National guidelines

A number of expert bodies have developed guidelines for the diagnosis and management of community-acquired pneumonia. The most often cited are the guidelines of IDSA and ATS.2 Thoughtful and comprehensive, these guidelines provide recommendations for the evaluation and treatment of the patient with community-acquired pneumonia driven by data, when available. Recommendations are classified by strength of supporting data; recommendations formed on the basis of opinion rather than data are identified. There is support for the use of the PSI and CRB scoring systems for risk stratification.

Treatment recommendationsare closely aligned with prior guidelines from the individual organizations. Compromise has been reached between the two organizations regarding the diagnostic evaluation of community-acquired pneumonia. Concerns of drug resistance and epidemiologic tracking have been noted, as have been concerns about lack of sensitivity and specificity in microbiologic testing. The resulting recommendations minimize testing for uncomplicated cases of pneumonia, allowing more extensive testing for sicker patients.

Guidelines for the home care of pneumonia have been published. These seek to ensure the administration of well-tolerated antimicrobial therapy and ongoing professional evaluation.18

When new respiratory pathogens emerge or major flares of well-known respiratory diseases occur, information develops quickly and guidelines are altered on a real-time basis. In such situations, the websites of the CDC, World Health Organization, IDSA, and state and local health departments often contain updated authoritative information and guidelines to assist the practitioner.

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Outcomes and performance measures

Pneumonia-related outcomes have been measured in several areas. In the area of microbiology, Metlay and colleagues have noted that patients with pneumococci not susceptible to penicillin are more likely to develop suppurative complications than patients infected with susceptible isolates.19 Overall, pneumococcal pneumonia has been shown by Fine and associates to carry a mortality rate of 12%.20 This level of mortality is exceeded only by Legionella species among community-acquired pathogens. Several pathogens more associated with long-term care facilities, including P. aeruginosa (61%) and S. aureus (32%), carry substantially higher mortality.

Samples for blood cultures drawn within 24 hours of hospital admission have been associated with improvement in 30-day mortality.21 Antibiotic therapy initiated within 4 hours of hospital admission has been shown to improve mortality and length of hospital stay in all pneumonia patients.5,22 Adherence to the IDSA guidelines for antimicrobial therapy improves mortality in patients with community-acquired pneumonia in intensive care units.23

With regard to site of care, the PORT data have suggested a less than 1% risk of 30-day mortality for pneumonia sufferers falling into risk classes I and II of the pneumonia severity index, suggesting the possibility of outpatient care for this group. A home hospital model of care with daily home physician visits can reduce the duration of acute care and overall treatment costs in older patients.24 IV-to-oral switch therapy has been shown to yield no significant reduction in outcome when the switch is instituted after clinical stability.12

The Centers for Medicare and Medicaid Services are moving forward with pay-for-performance measures, including certain parts of the IDSA/ATS practice guidelines, as a means of promoting hospital quality. Among the measures adopted are assessment of oxygenation, screening for pneumococcal vaccination, blood cultures before first antibiotic dose, assessment for smoking cessation, antibiotics within 4 to 6 hours of arrival at the hospital, and correct choice of antibiotics.

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References

  1. Hoyert DL, Heron MP, Murphy SL, Kung HC. Deaths: Final data for 2003. Natl Vital Stat Rep. 2006, 54: (13): 1-120.
  2. American Thoracic Society. Guidelines for the initial management of adults with community-acquired pneumonia: Diagnosis, assessment of severity, and initial antimicrobial therapy. Am J Resp Crit Care Med. 2001, 163: 1730-1754.
  3. Wiblin RT, Wenzel RP. Hospital-acquired pneumonia. Curr Clin Top Infect Dis. 1996, 16: 194-214.
  4. Bassin AS, Niederman MS. New approaches to prevention and treatment of nosocomial pneumonia. Semin Thorac Cardiovasc Surg. 1995, 7: 70-77.
  5. Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003, 37: 1405-1433.
  6. Kolleff MH, Micek ST. Methicillin-resistant Staphylococcus aureus—a new community-acquired pathogen? Curr Opin Infect Dis. 2006, 19: 161-168.
  7. Peiris JS, Yuen KY, Osterhaus AD, Stohr K. The severe acute respiratory syndrome. N Engl J Med. 2003, 349: 2431-2441.
  8. 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: 243-250.
  9. Lim WS, van der Eerden MM, Laing R, et al: Defining community acquired pneumonia severity on presentation to hospital: An international derivation and validation study. Thorax. 2003, 58: (5): 377-382.
  10. Mandell LA, Wunderink RG, Anzueto A, et al: Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007, 44: (Suppl 2): S27-S72.
  11. Murray PR, Washington JA. Microscopic and bacteriologic analysis of expectorated sputum. Mayo Clin Proc. 1975, 50: 339-344.
  12. Gleckman R, DeVita J, Hibert D, et al: Sputum gram stain assessment in community-acquired bacteremic pneumonia. J Clin Microbiol. 1988, 26: 846-849.
  13. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001, 50: 909-919.
  14. Cassiere HA, Fein AM. Duration and route of antibiotic therapy in patients hospitalized with community-acquired pneumonia: Switch and step-down therapy. Semin Resp Infect. 1998, 13: 36-42.
  15. Centers for Disease Control and Prevention. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2005, 54: (RR-08): 1-40.
  16. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1997, 46: (RR-08): 1-24.
  17. Centers for Disease Control and Prevention. Vaccines and preventable diseases: Combined Tdap vaccine. Available at http://www.cdc.gov/vaccines/vpd-vac/combo-vaccines/DTaP-Td-DT/tdap.htm(accessed March 9, 2009)
  18. Ramsdell J, Narsvage GL, Fink JB, et al: Management of community-acquired pneumonia in the home. Chest. 2005, 127: 1752-1763.
  19. Metlay JP, Hofmann J, Cetron MS, et al: Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia. Clin Infect Dis. 2000, 30: 520-528.
  20. Fine MJ, Smith MA, Carson CA, et al: Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis. JAMA. 1996, 274: 134-141.
  21. Arbo MDJ, Snydman DR. Influence of blood culture results on antibiotic choice in treatment of bacteremia. Arch Intern Med. 1994, 154: 2641.
  22. Houck PM, Bratzler DW, Nsa W, et al: Timing of antibiotic administration and outcomes for Medicare patients hospitalized with pneumonia. Arch Intern Med. 2004, 164: 637-644.
  23. Bodi M, Rodriguez A, Sole-Violan J, et al: Antibiotic prescription for community-acquired pneumonia in the intensive care unit: Impact of adherence to Infectious Diseases Society of America guidelines on survival. Clin Infect Dis. 2005, 41: 1709-1716.
  24. Leff B, Burton L, Mader SL, et al: Hospital at home: Feasibility and outcomes of a program to provide hospital-level care at home for acutely ill older patients. Ann Intern Med. 2005, 143: 798-808.

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Suggested Readings

  • American Thoracic Society. Guidelines for the initial management of adults with community-acquired pneumonia: Diagnosis, assessment of severity, and initial antimicrobial therapy. Am J Resp Crit Care Med. 2001, 163: 1730-1754.
  • Cassiere HA, Fein AM. Duration and route of antibiotic therapy in patients hospitalized with community-acquired pneumonia: Switch and step-down therapy. Semin Resp Infect. 1998, 13: 36-42.
  • Centers for Disease Control and Prevention. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2005, 54: (RR-08): 1-40.
  • Centers for Disease Control and Prevention. Prevention of pneumococcal disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1997, 46: (RR-08): 1-24.
  • Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001, 50: 909-919.
  • 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: 243-250.
  • Fine MJ, Smith MA, Carson CA, et al: Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis. JAMA. 1996, 274: 134-141.
  • Houck PM, Bratzler DW, Nsa W, et al: Timing of antibiotic administration and outcomes for Medicare patients hospitalized with pneumonia. Arch Intern Med. 2004, 164: 637-644.
  • Mandell LA, Bartlett JG, Dowell SF, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003, 37: 1405-1433.
  • Mandell LA, Wunderink RG, Anzueto A, et al: Infectious Diseases Society of America; American Thoracic Society: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007, 44: (Suppl 2): S27-S72.
  • Peiris JS, Yuen KY, Osterhaus AD, Stohr K. The severe acute respiratory syndrome. N Engl J Med. 2003, 349: 2431-2441.