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Community-Acquired Pneumonia

  • Paul Ellis Marik
Chapter

Abstract

In the United States, community-acquired pneumonia (CAP) in adults results in approximately 600,000 hospital admissions annually and ranks as the sixth leading cause of death. The mortality rate from CAP varies dramatically depending on the patient’s severity of illness at presentation and underlying comorbid conditions. In the outpatient setting, the mortality rate is <1–5%; however, once patients require hospitalization, the mortality rate approaches 12%. Of those patients with CAP hospitalized, between 18 and 36% require treatment in an ICU. The mortality of these patients is about 35%. While approximately 20% of patients admitted to the ICU with CAP are in septic shock, the mortality of these patients may be as high as 60%.

Keywords

Chronic Obstructive Pulmonary Disease Mycoplasma Pneumoniae Eosinophilic Pneumonia Cryptogenic Organize Pneumonia Influenza Pneumonia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

In the United States, community-acquired pneumonia (CAP) in adults results in approximately 600,000 hospital admissions annually and ranks as the sixth leading cause of death. The mortality rate from CAP varies dramatically depending on the patient’s severity of illness at presentation and underlying comorbid conditions. In the outpatient setting, the mortality rate is <1–5%; however, once patients require hospitalization, the mortality rate approaches 12%. Of those patients with CAP hospitalized, between 18 and 36% require treatment in an ICU. The mortality of these patients is about 35%. While approximately 20% of patients admitted to the ICU with CAP are in septic shock, the mortality of these patients may be as high as 60%.

The presence of underlying comorbid conditions such as
  • chronic obstructive pulmonary disease (COPD)

  • asthma

  • diabetes mellitus

  • renal insufficiency

  • congestive heart failure

  • coronary artery disease

  • malignancy

  • alcoholism

  • age >70 years

  • chronic neurological disease

  • chronic liver disease

not only contribute significantly to CAP morality but also may alter the etiologic organisms underlying the infection (see below).

ICU Admission Criteria

Major Criteria
  • Requirement for mechanical ventilation1 or

  • Septic shock (SBP <90 despite fluids)

Minor Criteria (Three or More)
  • 30 < white blood cell count <4 × 109/l

  • Blood urea nitrogen >20 mg/dl

  • PaO2/FiO2 <250

  • Multi-lobe involvement

  • Respiratory rate >30 breaths/min

  • Platelet count <100,000 × 109/l

  • Confusion/disorientation

  • Hypothermia (temperature <36°C)

  • Hypotension requiring fluid resuscitation

A review of those studies that have investigated the etiologic diagnosis in patients with severe CAP have isolated a pathogen in approximately 60% of patients, with the infection being polymicrobial in about 17% of patients. In these studies the most common pathogens were the following:
  • Streptococcus pneumoniae (15–46%)

  • Legionella species (0–23%)

  • Staphylococcus aureus (0–22%)

  • Haemophilus influenzae (0–14%)

  • Gram-negative bacilli (4–25%)

The classically described “atypical” pathogens that cause CAP include Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella species. The “atypical” moniker is an inaccurate description of the clinical features of the pneumonia associated with these organisms and is retained more as a classification than as a specific descriptor of the disease process or the clinical presentation. Mycoplasma pneumoniae has been shown to be the most common of the atypical pathogens and accounts for 17–37% of outpatient CAP and 2–33% of CAP requiring hospitalization. Chlamydia pneumoniae is more common than Legionella species; however, Legionella species can lead to rapidly progressive and fatal pneumonia.

Pathogens Associated with Underlying Comorbid Condition

  • S. pneumoniae
    • Dementia

    • Congestive heart failure

    • COPD

    • Cerebrovascular disease

    • Institutional crowding

    • Seizures

  • Penicillin-resistant and drug-resistant pneumococcus
    • Age >65 years

    • Alcoholism

    • Immunomodulating illness or therapy (including steroids)

    • Previous β-lactam therapy within 3 months

    • Multiple medical comorbidities

    • Exposure to child in day care center

  • Enteric gram negatives
    • Residence in long-term facility

    • Underlying cardiopulmonary disease

    • Recent antibiotic therapy

    • Multiple medical comorbidities

  • Pseudomonas aeruginosa
    • Broad-spectrum antibiotics for >7 days in the past month

    • Structural lung disease (bronchiectasis)

    • Corticosteroid therapy

    • Malnutrition

    • Undiagnosed HIV infection

    • Neutropenia

  • Legionnaires’ disease
    • AIDS

    • Hematologic malignancy

    • End-stage renal disease

Diagnostic Testing

Patients with severe CAP should have the following:
  • Blood cultures.

  • Urinary antigen tests for Legionella pneumophila and S. pneumoniae.

  • Expectorated sputum for culture.

  • Intubated patients require endotracheal aspirate (fresh) or m-BAL.

  • Screening for HIV.

  • Nasopharyngeal swab for influenza during seasonal influenza (rapid Ag test and viral PCR)

The only randomized controlled trial evaluating a diagnostic strategy in CAP demonstrated no statistically significant differences in mortality or LOS between patients receiving pathogen-directed therapy and patients receiving empiric therapy.2 However, pathogen-directed therapy was associated with lower mortality among the patients admitted to the ICU.

Non-infectious diseases masquerading as CAP should be excluded, namely:
  • Cryptogenic organizing pneumonia (COP)

  • Eosinophilic pneumonia

  • Hypersensitivity pneumonia

  • Drug-induced pneumonitis: methotrexate, nitrofurantoin, gold, amiodarone, etc

  • Pulmonary vasculitis

  • Pulmonary embolism/infarction

  • Pulmonary malignancy

  • Radiation pneumonitis

  • Tuberculosis

Antibiotic Treatment (ICU Patients)

First Choice
  • β-Lactam1
    • Cefotaxime

    • Ceftriaxone

    • Ampicillin–sulbactam

    PLUS

  • Azithromycin or fluoroquinolone

Penicillin Allergy
  • Fluoroquinolone

    PLUS

  • Aztreonam

Pseudomonal Infection
  • Anti-pneumococcal, anti-pseudomonal β-lactam
    • Piperacillin–tazobactam

    • Cefepime

    • Imipenem

    • Meropenem

PLUS
  • Ciprofloxacin or levofloxacin (750 mg)

  • OR
    • Anti-pneumococcal, anti-pseudomonal β-lactam

    PLUS
    • Aminoglycoside and azithromycin

  • OR
    • Anti-pneumococcal, anti-pseudomonal β-lactam

    PLUS
    • Aminoglycoside and anti-pneumococcal fluoroquinolone

Penicillin allergic
  • Aztreonam

PLUS
  • Aminoglycoside and anti-pneumococcal fluoroquinolone

Community-Acquired MRSA

Influenza (Coexistent or Influenza Pneumonia)

  • Early treatment (within 48 h of the onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A.

  • Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for >48 h, but these drugs may be used to reduce viral shedding in hospitalized patients or for influenza pneumonia.

  • Streptococcus pneumoniae and S. aureus are the most common causes of secondary bacterial pneumonia in patients with influenza.

Supportive Care

See  Chapter 10.

Special Considerations

Double Cover for CAP

Although monotherapy is considered as standard for CAP, a survival benefit of the combination of β-lactam and macrolide has been suggested. Waterer3 found that patients with bacteremic pneumococcal CAP who receive at least two effective antibiotic agents within the first 24 h after presentation to hospital have a significantly lower mortality than do patients who receive only one effective antimicrobial agent. The most common combination was a third-generation cephalosporin with a macrolide or a quinolone. Using a large hospital database, Brown et al.4 demonstrated a lower mortality, shorter LOS, and lower hospital charges for patients with CAP treated with dual therapy using macrolides as the second agent. Rodriguez et al. undertook a secondary analysis of data obtained from a prospective observational cohort study of cases in 33 ICUs in Spain. Overall, 270 patients required vasoactive drugs and were characterized as having shock. In the cases with shock, combination antibiotic therapy was associated with a significantly higher adjusted 28-day in-ICU survival (hazard ratio 1.69; 95% CI 1.09–2.60; p = 0.01).5 Another study investigated the outcome of patients with severe CAP, comparing patients treated with β-lactam/macrolide combination vs. those treated with fluoroquinolone monotherapy.6 Lower 30-day mortality rates were seen for those treated with β-lactam/macrolide combination (18.4% vs. 36.6%, p = 0.05).

The possible explanations for the benefits of dual coverage (esp. with a macrolide) include antibiotic synergy, coverage of unrecognized atypical pathogens, immunomodulating effects, and the effect on bacterial quorum sensing. Macrolides, at sub-minimum inhibitory concentrations (MIC), are potent inhibitors of the production of pneumolysin (a potent virulence factor) by macrolide-susceptible strains of the pneumococcus, whereas the β-lactam agent ceftriaxone, as well as amoxicillin, ciprofloxacin, moxifloxacin, and tobramycin, is relatively ineffective.7 Although they also antagonize various pro-inflammatory activities of neutrophils, macrolides primarily target the synthesis of interleukin (IL)-8 by bronchial epithelial cells, eosinophils, monocytes, fibroblasts, and airway smooth muscle cells.8 While there is no definitive evidence that combination therapy improves outcome, dual therapy with a macrolide and a third-generation cephalosporin should be considered in patients with severe CAP.

Community-Acquired MRSA Pneumonia (CA-MRSA)

Recently, an increasing incidence of pneumonia due to CA-MRSA has been observed.9, 10, 11 CA-MRSA appears in two patterns: the typical hospital-acquired strain and a strain that is epidemiologically, genotypically, and phenotypically distinct from hospital-acquired strains. Many of the former may represent health-care-associated CAP (HCAP). The latter are resistant to fewer anti-microbials than are hospital-acquired MRSA strains and often contain a novel type IV SCCmec gene. In addition, most contain the gene for Panton-Valentine leucocidin, a toxin associated with clinical features of necrotizing pneumonia, shock, and respiratory failure, as well as the formation of abscesses and empyemas. This strain should also be suspected in patients who present with cavitary infiltrates without risk factors for anaerobic aspiration pneumonia. Diagnosis is usually straightforward, with high yields from sputum and blood cultures in this characteristic clinical scenario. CA-MRSA CAP remains rare in most communities but is expected to be an emerging problem in CAP treatment.

Health-Care-Associated Pneumonia

Patients who develop pneumonia in the setting of an acute or a chronic health-care facility must be distinguished from those who develop pneumonia in the community; these patients are referred to as having health-care-associated pneumonia, which includes hospital-acquired pneumonia and ventilator-associated pneumonia. (See  Chapter 17.) This distinction is important as these patients are at high risk for having infection with MRSA and multi-drug-resistant (MDR) bacterial pathogens. The MDR pathogens include P. aeruginosa, extended-spectrum β-lactamase-producing Klebsiella pneumoniae, Acinetobacter baumannii, Enterobacter species and Enterococcus species. Early broad-spectrum anti-microbial coverage with multiple antibiotics is recommended in these patients, with de-escalation once the implicated pathogen has been identified In general, this requires the combination of an anti-pseudomonal cephalosporin (cefepime, ceftazidime), carbapenem (imipenem, meropenem), or penicillin (piperacillin/tazobactam) plus either an anti-pseudomonal fluoroquinolone or aminoglycoside.

Persistent Temperature/Failure to Respond to Rx

A common misconception is that the patient’s temperature should settle within 24 h of commencing antibiotic therapy. It has been demonstrated that it may take up to 72 h for the temperature to normalize in a patient with pneumococcal pneumonia. However, in a patient with a widely swinging temperature, it would be prudent to exclude a complication within this time frame. The following are the major reasons for a failure to respond to anti-microbial agents:
  • Wrong antibiotic: wrong spectrum or drug resistance

  • Exclude masquerader

  • Wrong dosage

  • Viral, fungal, or opportunistic pathogen

  • Unusual pathogens (see below)

  • Superadded complication

  • Complicated pleural effusion/empyema

  • Endocarditis

  • Purulent pericarditis

  • Septic arthritis

  • Meningitis, etc.

Unusual Pathogens

  • Coxiella burnetii
    • Cats, goats, sheep, cattle

  • Tularemia
    • Rabbits, ticks

  • Leptospirosis
    • Rats

  • Hantavirus
    • Rats

  • SARS

  • Psittacosis
    • Birds

  • Nocardia
    • Steroids

  • Aspergillus
    • Steroids

  • Pneumocystis jiroveci
    • Immunosuppression

  • Dimorphic fungi
    • Recent travel

  • Burkholderia pseudomallei
    • Recent travel

  • TB

Complicated Pleural Effusion/Empyema

When pleural fluid is detected in a patient with pneumonia, a diagnostic thoracocentesis should always be performed to rule out pleural space infection (except if the effusion is very small). Pleural fluid studies differentiate between a benign parapneumonic effusion and an early empyema (complicated pleural effusion). Drainage is necessary when the pleural fluid is grossly purulent or if pleural fluid studies show any of the following:
  • pH <7.2 (most sensitive indicator)

  • Glucose <40 mg/dl

  • White blood cell count >10,000/ml

Clinical Pearls

  • The combination of a third-generation cephalosporin and a macrolide is the preferred treatment option for patients with severe CAP.

  • Always exclude conditions that may masquerade as CAP.

  • Always obtain travel history and history of contacts with animals, i.e., unusual pathogens.

  • Consider community-acquired MRSA in toxic patients and those with severe disease.

  • Consider P. aeruginosa risk factors.

References

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Pulmonary and Critical Care MedicineEastern Virginia Medical SchoolNorfolkUSA

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