34 Community-Acquired and Hospital-Acquired Pneumonia

Question 1

Epidemiology

• Pneumonia
• Pneumonia in the immunocompetent host
• Pneumonias in immunocompromised hosts

Answer 1

• Pneumonia
  
  • Infection of the gas exchanging or alveolar compartment of the lung
  • A common clinical problem that accounts for significant morbidity and mortality
• Pneumonia in the immunocompetent host
  
  • Broadly classified as “community-acquired” or “hospital-acquired”
  • The pathogens involved, empiric antibiotic therapy, and prognosis differ between the two entities.
• Pneumonias in immunocompromised hosts
  
  • Such as individuals with Human Immunodeficiency Virus (HIV) infection, transplant recipients, and patients with neutropenia (neutrophil counts <500)
  • Distinguished from community-acquired and nosocomial pneumonia, since a unique set of pathogens must be considered in immunocompromised patients

Question 2

Epidemiology:
Community-acquired pneumonia (CAP)

• Refers to…
• Generally does not include patients who have evidence for…
• Residents of nursing homes
• Prevalence
• Mortality rates

Answer 2

• Refers to…
  
  • Pneumonia acquired in the community (as opposed to the hospital) in an immunocompetent host
• Generally does not include patients who have evidence for…
  
  • Significant aspiration
  • Bronchial obstruction
  • Chronic pneumonia as caused by fungi or tuberculosis
• Residents of nursing homes
  
  • Considered by some investigators to be residing in the community
  • Others have excluded nursing home residents from studies of CAP
• Prevalence
  
  • ~ 5 million cases of CAP a year in the U.S. alone
    
    • Of these, ~20% require hospitalization
  • 6th leading cause of death in the US
• Mortality rates
  
  • Vary from <5% in those not requiring hospitalization, to approximately 25% among patients requiring hospitalization

Question 3

Epidemiology:
Hospital-acqruied pneumonia (HAP)

• Refers to…
• Prevalence
• Mortality rates

Answer 3

• Refers to…
  
  • Pneumonia that develops more than 48 hours after hospital admission
• Prevalence
  
  • 2nd most common hospital-acquired infection
  • Occurs in as many as 1% of all hospital admissions
• Mortality rates
  
  • Significantly higher than from community-acquired pneumonia
  • Approach 50% in some series

Question 4

Pathogenesis and pathology:
In the healthy state

• The respiratory tract below the vocal cords
• The upper airway (above the vocal cords, including naso- and oropharynx)
• The resident flora
• Host defense mechanisms
• Upper airway defense mechanisms

Answer 4

• The respiratory tract below the vocal cords
  
  • Sterile, that is, free of bacteria
• The upper airway (above the vocal cords, including naso- and oropharynx)
  
  • Normally inhabited by a host of bacteria that constitute the “normal respiratory flora” (including viridans streptococci, micrococci, Neisseria spp and Candida among others)
• The resident flora
  
  • Thought to contribute to host defense by competing with potential pathogens for nutrients and binding sites
• Host defense mechanisms
  
  • Have evolved to maintain sterility of the lower respiratory tract in the face of exposure to bacteria and viruses by aspiration from the upper airway and/or aerosolization from the environment
• Upper airway defense mechanisms
  
  • Fltering via the nasal passage and oropharynx
  • Sloughing of epithelial cells for clearance
  • Mucociliary transport from the nasal passages
  • The sneeze reflex
  • Nasal secretions that contain a variety of antimicrobial substances
    
    • Defensins (anti-microbial peptides)
    • Lactoferrin
    • Lysozyme
    • Immunoglobulin A (IgA)

Question 5

Pathogenesis and pathology:
In the healthy state

• Defense mechanisms within the glottis
• Defense mechanisms within the trachea and conducting airways (bronchi and bronchioles)
• If microbes evade these relatively nonspecific defense mechanisms,…
• An inflammatory response initiated by the macrophage leads to…

Answer 5

• Defense mechanisms within the glottis
  
  • Glottic closure
  • The cough reflex
• Defense mechanisms within the trachea and conducting airways (bronchi and bronchioles)
  
  • The bifurcating airway impedes direct access to the alveolar space
  • Impaction of large particles on this surface defends the airspace against infection
  • Once entangled in the mucus layer of the conducting airways, particles are transported via the mucociliary escalator for cough clearance or swallowed from the oropharynx
  • Antimicrobial substances provide defense against microbial proliferation
• If microbes evade these relatively nonspecific defense mechanisms,…
  
  • Other components of the lung defense system, such as immunoglobulins, alveolar macrophages, and surfactant proteins or collectins serve to thwart microbial invasion of the airspace
• An inflammatory response initiated by the macrophage leads to…
  
  • Neutrophil recruitment from the vascular space to airway, providing a final line of defense against infection

Question 6

Pathogenesis and pathology

• Disruption of any component of these defense mechanisms predisposes to…
• Examples
• Interestingly, approximately 50% of normal individuals aspirate…
• That pneumonia is not observed more frequently consequent to the high concentration of bacteria in oral secretions speaks for…
• Hematogenous seeding of the lung

Answer 6

• Disruption of any component of these defense mechanisms predisposes to…
  
  • Infection of the lower airway
• Examples
  
  • The effects of tobacco smoke on ciliary function and mucociliary clearance
  • Impairment of the cough reflex in the setting of neurologic impairment
  • Bypassing of the upper airway via tracheostomy or endotracheal intubation
  • Viral infection (particularly influenza) with its adverse affects on mucociliary clearance
• Interestingly, approximately 50% of normal individuals aspirate…
  
  • Small amounts of oropharyngeal secretions during sleep
• That pneumonia is not observed more frequently consequent to the high concentration of bacteria in oral secretions speaks for…
  
  • The effectiveness of normal host defense mechanisms at preventing lower airway infection (bronchitis, bronchiolitis, and pneumonia)
• Hematogenous seeding of the lung
  
  • Occurs much less commonly than infection via aspiration or aerosolization into the tracheobronchial tree
  • Can lead to the development of pneumonia
  • Most often seen in patients with right-sided bacterial endocarditis due to Staphylococcus aureus
    
    • IV drug use as risk factor

Question 7

Pathogenesis and pathology:
Aspiration pneumonitis

• General
• Occurs most often with…
• The lung injury
• Phases of aspiration
• After aspiration, the patient may develop…
• The aspirated contents
• The inflammatory response

Answer 7

• General
  
  • An acute lung injury after inhalation of regurgitated gastric contents
• Occurs most often with…
  
  • Altered consciousness (intoxications)
  • Swallowing problems after a stroke
• The lung injury
  
  • Depends on the pH of aspirated gastric contents
  • Causes a chemical burn of the tracheobronchial tree and pulmonary parenchyma leading to inflammation
• Phases of aspiration
  
  • 1st phase: seen within 1-2 hour due to the direct effect of acid
  • 2nd pahse: after 4-6 hours during which neutrophils infiltrate into the alveoli
• After aspiration, the patient may develop…
  
  • A fever, leucocytosis and a short-lived infiltrate on Chest X-ray
  • Mimicks infectious pneumonia
• The aspirated contents
  
  • Most often sterile (since gastric pH is so low)
• The inflammatory response
  
  • Usually resolves within 48 hours and does not need antibiotic treatment
  • If the stomach or oropharynx is heavily colonized with gram negative rods and/or the patient is at very high risk for complications, a short course of appropriate antibiotics can be considered

Question 8

Pathogenesis and pathology:
Lobular pneumonia (bronchopneumonia)

• Refers to…
• Frequency
• Pathologic findings
• With bacterial pneumonia,…
• Typically, with resolution of infection,…
• Uncommonly, and with particularly virulent organisms (Staphylococcus aureus, for example),…

Answer 8

• Refers to…
  
  • Patchy consolidation of the lung
• Frequency
  
  • This pattern is the most common pathologic manifestation of bacterial pneumonia
  • Any pathogen can lead to bronchopneumonia
• Pathologic findings
  
  • Areas of inflammation in the bronchi
  • Bronchioles
  • Alveolar space within one or more lobes of the lung
• With bacterial pneumonia,…
  
  • Neutrophils predominate
  • There is a proteinaceous exudate that fills the alveolar spaces
• Typically, with resolution of infection,…
  
  • The inflammatory process resolves
  • Alveolar architecture returns to normal
• Uncommonly, and with particularly virulent organisms (Staphylococcus aureus, for example),…
  
  • There is necrosis within the areas of lung inflammation, leading to abscess formation

Question 9

Pathogenesis and pathology:
Lobar pneumonia

• Refers to…
• Typically caused by…
• Characterized by…
• Inflammatory response
• Resolution often occurs…

Answer 9

• Refers to…
  
  • Infection involving most or all of a lobe of the lung
• Typically caused by…
  
  • Streptococcus pneumoniae
• Characterized by…
  
  • Widespread inflammatory exudate in the alveolar space
• Inflammatory response
  
  • Acute neutrophilic inflammation is typically followed by the accumulation of fibrin in the alveolar space, without destruction of the alveolar walls
• Resolution often occurs…
  
  • Over several days, with digestion of the fibrinous exudate leading to resorption, expulsion via cough, or digestion by macrophages
  • Alveolar architecture often returns to normal

Question 10

Pathogenesis and pathology:
Interstitial pneumonia

• Refers to…
• This pathologic lesion is characteristic of…
• May be seen with…
• In severe cases, there is…
• Resolution of the infection

Answer 10

• Refers to…
  
  • Iinflammation that is largely confined to the alveolar wall
  • Leukocyte infiltration and edema but no filling of the alveolar space
• This pathologic lesion is characteristic of…
  
  • Viral infections (particularly influenza)
• May be seen with…
  
  • “Atypical” pathogens such as Mycoplasma pneumonia
• In severe cases, there is…
  
  • Desquamation of alveolar epithelial cells with fluid and/or blood accumulation in the alveolar space
  • This may lead to filling of the alveolar space (consolidation), or the formation of hyaline membranes
• Resolution of the infection
  
  • As with broncho-and lobar pneumonia, is typically followed by restoration of normal lung structure and function
  • Less commonly, interstitial inflammation leads to scarring in the form of alveolar fibrosis

Question 11

Community-acquired pneumonia (CAP):
The most common pathogens associated with each category

• Outpatient, no co-morbidities
• Outpatient, co-morbidity (COPD, diabetes, renal or congestive heart failure, malignancy)
• Hospitalized
• Hospitalized, severe disease

Answer 11

• Outpatient, no co-morbidities
  
  • Streptococcus pneumoniae
  • Mycoplasma pneumoniae
  • Chlamydophila pneumoniae
  • Viruses (adenovirus, influenza, RSV, metapneumovirus, and others)
  • Haemophilus influenza
  • Legionella
• Outpatient, co-morbidity (COPD, diabetes, renal or congestive heart failure, malignancy)
  
  • Streptococcus pneumoniae
  • Mycoplasma pneumoniae
  • Chlamydophila pneumoniae
  • Viruses (adenovirus, influenza, RSV, metapneumovirus, and others)
  • Haemophilus influenza
  • Legionella
• Hospitalized
  
  • Streptococcus pneumoniae
  • Haemophilus influenza
  • Polymicrobial
  • Viruses (adenovirus, influenza, RSV, metapneumovirus, and others)
  • Legionella
• Hospitalized, severe disease
  
  • Streptococcus pneumoniae
  • Viruses (adenovirus, influenza, RSV, metapneumovirus, and others)
  • Legionella
  • Pseudomonas aeruginosa and other Gram-negative bacilli
  • Staphylococcus aureus

Question 12

Community-acquired pneumonia (CAP):
Two important points need to be made with regard to the etiology of CAP

• Identifying pathogens responsible for CAP
• Prominent causative organisms
• ​“Atypical” organisms
• Pseudomonas aeruginosa

Answer 12

• No pathogen responsible for community-acquired pneumonia is identified in up to 50% of patients, despite earnest attempts to identify an organism
• In every category (outpatient, no comorbidities; outpatient, comorbidities; hospitalized; hospitalized, severe disease), Streptococcus pneumoniae and “atypical” organisms (Mycoplasma pneumoniae, Chlamydophilia pneumoniae and Legionella) feature prominently in the list of causative organisms
  
  • Therefore, all empiric treatment regimens for CAP must cover both Streptococcus pneumoniae and the “atypical” organisms
• ​“Atypical” organisms
  
  • Bacteria which are not visualized on Gram stain and will not readily grow on agar plates routinely used to culture bacteria
  • Examples of these bacteria include Mycoplasma pneumoniae, Chlamydiophilia pneumoniae and Legionella species
• Pseudomonas aeruginosa
  
  • Rarely a cause of CAP
  • Only needs to be covered with specific antipseudomonal antibiotic therapy in certain patients admitted to intensive care units (ICUs) with CAP
  • Risk factors for Pseudomonas infection
    
    • Severe structural lung disease (eg, bronchiectasis)
    • Recent antibiotic therapy
    • Recent stay in hospital (especially in the ICU)

Question 13

Hospital-acquired pneumonia (HAP):
Etiology

• Early-onset VAP
  
  • Occurs…
  • Associated with…
  • Key pathogens
• Late-onset VAP
  
  • Due to…
  • Typical pathogens
  • Typified by…
• Non-ventilator-associated hospital-acquired pneumonia
  
  • General
  • Common pathogens

Answer 13

• Early-onset VAP
  
  • Occurs within the first week of mechanical ventilation
  • Associated with upper respiratory flora
  • Key pathogens: Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus
• Late-onset VAP
  
  • Due to micro-aspiration of the more resistant bacteria replacing normal upper respiratory flora due to cross contamination and antibiotic pressures in the ICU
  • Typical pathogens: Pseudomonas aeruginosa, Staphylococcus aureus (typically methicillin resistant), and enteric Gram negative bacilli (Klebsiella pneumoniae, Enterobacter cloacae etc)
  • Typified by antibiotic resistant organisms making treatment difficult
• Non-ventilator-associated hospital-acquired pneumonia
  
  • Heterogeneous condition that in many cases may be associated with aspiration
  • Common pathogens: enteric Gram negative bacilli (Escherichia coli, Klebsiella, Proteus mirabilis, Serratia marcescens), sometimes anaerobic Gram negative bacilli, Haemophilus influenzae, Staphylococcus aureus and occasionally Streptococcus pneumoniae

Question 14

Symptoms and signs

• Typical findings are often absent in…
• Classical symptoms of pneumonia
• Typical bacterial pneumonia
• Physical findings
• Chest exam

Answer 14

• Typical findings are often absent in…
  
  • The elderly
• Classical symptoms of pneumonia
  
  • Cough, fever, and shortness of breath
• Typical bacterial pneumonia
  
  • Begins with chills or rigors
  • Followed by fever, cough productive of purulent or rusty sputum, and shortness of breath
  • Chest pain may occur in up to a third of patients, and is often pleuritic in character due to pleural inflammation.
• Physical findings
  
  • Fever (present in most patients but less reliable as a finding in the elderly), tachypnea, and tachycardia
• Chest exam
  
  • Crackles over the involved area of lung
  • With more extensive disease, there may be findings of consolidation (dullness to percussion, tubular or bronchial breath sounds, and/or egophony and increased tactile fremitus)
  • In contrast, pleural effusion or empyema (infection of the pleural space) associated with pneumonia that involves an area of lung adjacent to the pleural surface, should be suspected when there is dullness to percussion with diminished breath sounds and decreased tactile fremitus

Question 15

Symptoms and signs

• Ventilated or neurologically impaired patients
• The diagnosis of hospital-acquired pneumonia
• Fever
• Clinical findings of crackles or those consistent with pleural effusions
• Ventilated patients
  
  • Spontaneous expectoration of sputum
  • Clues to pneumonia in this patient population

Answer 15

• Ventilated or neurologically impaired patients
  
  • May not be able to provide any history
• The diagnosis of hospital-acquired pneumonia
  
  • May be difficult
• Fever
  
  • Typical in patients with pneumonia
  • Seriously ill patients may have multiple potential causes for fever
• Clinical findings of crackles or those consistent with pleural effusions
  
  • May have etiologies other than pneumonia in such patients
• Ventilated patients
  
  • Spontaneous expectoration of sputum is not possible
  • Clues to pneumonia in this patient population
    
    • Increased need for suctioning
    • Purulent respiratory secretions
    • Increased oxygen requirements

Question 16

Laboratory findings

• Often…
• With most bacterial infections
• With most bacterial infections

Answer 16

• Often…
  
  • Non-specific
• With most bacterial infections
  
  • Leukocytosis with left shift (presence of bands and other immature neutrophil precursors in the peripheral blood)
• With severe or overwhelming pneumonia
  
  • May be leukopenia

Question 17

Laboratory findings:
Community-acquired pneumonia (CAP):
Gram stain

• Pros
• May be useful…

Answer 17

• Non-invasive and relatively inexpensive way to determine a pathogen for the clinical diagnosis of pneumonia
• May be useful
  
  • When a purulent specimen (>25 neutrophils/low power field with < 10 epithelial cells) is obtained that reveals a predominant organism
    
    • Ex. sheets of gram positive diplococci in pneumococcal pneumonia
  • If a purulent specimen does not contain abundant gram negative rods

Question 18

Laboratory findings:
Community-acquired pneumonia (CAP):
Sputum culture

• May be useful if they…
• Negative cultures
• Cons
• CAP vs. HAP
• Cultures from other sites that may be involved with the acute infection
• Blood and pleural fluid

Answer 18

• May be useful if they…
  
  • Contain a predominant organism in moderate or heavy growth
  • Identify an organism that does not typically colonize the respiratory tract
• Negative cultures
  
  • Have no predictive value for the exclusion of pneumonia
• Cons
  
  • ~1/3 of patients with pneumonia do not produce sputum
  • Sensitivity and specificity of sputum studies are poor
  • With current antibiotics, identification of a pathogen in sputum is not likely to alter empiric management
  • Sputum findings do not allow differentiation between infection and airway colonization
• CAP vs. HAP
  
  • Although this is not often a problem in CAP, HAP patients often become “colonized” with potential pathogens
  • The predictive value of a sputum culture in this setting is poor.
• Cultures from other sites that may be involved with the acute infection
  
  • More easily interpreted
  • Of value in patients with CAP requiring hospitalization
• Blood and pleural fluid
  
  • Normally sterile
  • Positive cultures in the setting of pneumonia indicate the presence of the pathogen in the lung

Question 19

Laboratory findings:
Community-acquired pneumonia (CAP):
Pathogen specific tests

• Use is reserved for…
• Urine detection
  
  • Possible for…
  • Potential advantage
  • Con
• Serology
  
  • Available for…
  • Limiting factor
  • Follow-up
  • Con

Answer 19

• Use is reserved for…
  
  • Patients with CAP of sufficient severity to warrant hospitalization
• Urine detection
  
  • Possible for Legionella pneumophila or Streptococcus pneumoniae antigens
  • Potential advantage of providing a more rapid diagnosis than with culture
  • The Legionella urinary antigen test does not detect species other than Legionella pneumophila so does not “rule out” legionellosis
• Serology
  
  • Available for Chlamydophila pneumoniae, Mycoplasma pneumoniae and viral causes of CAP
  • A limiting factor: specimens collected at the time of a patient’s presentation may be falsely negative (IgG) or false positive due to low specificity (IgM)
  • A follow-up (“convalescent”) sample (IgG) 10-14 days after the onset of symptoms is more likely to be positive
  • The lack of timeliness of such results means that patients will either be cured or be dead by the time serology confirms the diagnosis

Question 20

Laboratory findings:
Ventilator-associated pneumonia

• The presence of a tube in the trachea…
• Endotracheal aspirates
• Bronchoalveolar lavage (BAL)
• Indicator of a true cause of VAP rather than an organism which is merely colonizing the respiratory tract

Answer 20

• The presence of a tube in the trachea…
  
  • Facilitates collection of respiratory tract specimens in ventilated patients
• Endotracheal aspirates
  
  • Frequently collected in ICU patients
  • May be difficult to interpret because of the possibility of respiratory tract colonization
• Bronchoalveolar lavage (BAL)
  
  • Performed with quantitative culture of this specimen to avoid this difficulty in interpretation
• Indicator of a true cause of VAP rather than an organism which is merely colonizing the respiratory tract
  
  • Growth of more than 10,000 organisms/mL BAL fluid

Question 21

Radiographic findings

• Alveolar patterns
• Interstitial patterns
• Chest x-ray
  
  • Diagnosis
  • Quality
  • Vs. clinical findings
  • 2D x-ray
  • Plain x-rays
  • Inter-observer variation
  • CT scanning

Answer 21

• Alveolar patterns
  
  • Refer to airspace filling by fluid (blood, pus, or water/edema) or tumor
  • Air bronchograms
    
    • Densities in alveolar disease are often confluent, and when present around airways, create a contrast that makes the airway segment apparent
• Interstitial patterns
  
  • Refer to fine linear densities or very small nodules
• Chest x-ray
  
  • Diagnostic of pneumonia
  • The quality is important, with portable chest x-rays being poorly standardized and often providing lower quality images than standard Posterior-Anterior (PA) and lateral chest x-rays
  • May “lag” behind the clinical findings
    
    • Patients presenting with classic signs and symptoms of pneumonia may have a radiographic abnormality that is only apparent several days after presentation
  • The two dimensional x-ray will fail to disclose an abnormality that is conspicuous on Computerized Tomography (CT) scanning
  • Plain x-rays are not 100% sensitive for the detection of pneumonia
  • Inter-observer variation is in part related to experience
    
    • The cross sectional view and increased resolution provided by CT scanning has contributed to increased sensitivity for the early detection of pulmonary infiltrates in immunocompromized hosts
  • It is likely that CT scanning has higher sensitivity than plain radiographs for detection of pulmonary infiltrates

Question 22

Radiographic findings:
Common radiographic manifestations of organisms responsible for most pneumonias

• Streptococcus pneumoniae, Haemophilus influenzae, and Gram-negative bacilli
  
  • Typical clinical features
  • Typical CXR appearance
• Mycoplasma pneumoniae
  
  • Typical clinical features
  • Typical CXR appearance
• Chlamydophila pneumoniae
  
  • Typical clinical features
  • Typical CXR appearance
• Legionella pneumophila
  
  • Typical clinical features
  • Typical CXR appearance
• Influenza viruses
  
  • Typical clinical features
  • Typical CXR appearance

Answer 22

• Streptococcus pneumoniae, Haemophilus influenzae, and Gram-negative bacilli
  
  • Typical clinical features
    
    • Rapid onset
    • Fever/chills, pleurisy, cough with sputum
  • Typical CXR appearance
    
    • Alveolar pattern, sometimes lobar in distribution
• Mycoplasma pneumoniae
  
  • Typical clinical features
    
    • Dry cough, subacute onset in young adult
  • Typical CXR appearance
    
    • Interstitial pattern
• Chlamydophila pneumoniae
  
  • Typical clinical features
    
    • Upper respiratory symptoms (sore throat, hoarseness) common; subacute with dry cough
  • Typical CXR appearance
    
    • Alveolar pattern, often patchy and segmental
• Legionella pneumophila
  
  • Typical clinical features
    
    • Cough with or without sputum, acute or subacute presentation, extrapulmonary manifestations (abnormal liver enzymes, CNS symptoms)
  • Typical CXR appearance
    
    • Alveolar pattern, from patchy to more extensive consolidation
• Influenza viruses
  
  • Typical clinical features
    
    • Follows typical flu-like illness (high fever, headache, myalgias)
  • Typical CXR appearance
    
    • Interstitial pattern, typically bilateral

Question 23

Diagnosis:
Community-acquired pneumonia (CAP)

• The clinical symptoms that should raise suspicion of pneumonia
• Other diagnoses to consider in this setting
• Criteria to diagnose CAP
• Diagnosis therefore rests on…
• Chest radiographic abnormality
• Diagnosis in patients with mild or early disease may rely on…
• Patients who present critically ill with clinical signs and symptoms of pneumonia but a negative chest x-ray
• CT scanning
• CT angiography

Answer 23

• The clinical symptoms that should raise suspicion of pneumonia
  
  • Cough, fever, and dyspnea, with or without sputum production and chest pain
• Other diagnoses to consider in this setting
  
  • Other infectious diseases of the lung, such as bronchitis or bronchiolitis
  • Pulmonary embolism
  • A variety of noninfectious inflammatory lung diseases, such as pulmonary fibrosis, hypersensitivity pneumonitis, bronchiolitis obliterans, and sarcoidosis
• Criteria to diagnose CAP
  
  • There is no specific set of criteria to make a diagnosis of CAP
  • Identification of an organism associated with pneumonia is not required for diagnosis
• Diagnosis therefore rests on…
  
  • Some combination of clinical symptoms, exam findings, and radiographic demonstration of a new abnormality
• Chest radiographic abnormality
  
  • Generally used as the gold standard
  • The plain chest radiograph may be normal in pneumonia
• Diagnosis in patients with mild or early disease may rely on…
  
  • Clinical findings
  • In the face of compelling historical and physical exam findings, chest radiographs are not necessary for patients who do not require hospitalization
• Patients who present critically ill with clinical signs and symptoms of pneumonia but a negative chest x-ray
  
  • Should be treated empirically with antibiotics and evaluated with additional diagnostic studies, such as chest CT
• CT scanning
  
  • Often useful to confirm the diagnosis of pneumonia
  • May suggest other possible diagnoses
• CT angiography
  
  • Allows evaluation of the pulmonary vasculature for embolic disease and lung parenchyma for pneumonia and other pulmonary diseases
  • Appears advantageous in cases of diagnostic uncertainty

Question 24

Diagnosis:
Hospital-acquired pneumonia (HAP)

• The clinical approach relies on…
• These criteria appear to be…
• What may present with symptoms and signs suggestive of pneumonia
• Clinical pulmonary infection score (CPIS)

Answer 24

• The clinical approach relies on…
  
  • Criteria similar to those used to diagnose community-acquired pneumonia
  • The presence of a new pulmonary infiltrate and clinical evidence for pneumonia (fever, cough with purulent sputum, and/or elevated white count)
• These criteria appear to be…
  
  • Overly sensitive
  • Many patients with this constellation of symptoms will not, in fact, have lower respiratory tract infection
• What may present with symptoms and signs suggestive of pneumonia
  
  • Pulmonary embolism, atelectasis, drug reactions, congestive heart failure and non-infectious inflammatory lung diseases
  • The airways of hospitalized patients often become colonized with bacteria, which markedly decreases the positive predictive value of culture of endotracheal aspirates
• Clinical pulmonary infection score (CPIS)
  
  • Given the uncertainties noted above, this scoring system has been developed which assigns points to clinical signs, radiographic signs and Gram stain results

Question 25

Diagnosis:
Hospital-acquired pneumonia (HAP)

• Bronchoscopy
• PSB
• BAL
• Problems with this approach
• Cultures of blood and pleural fluid

Answer 25

• Bronchoscopy
  
  • Determines the presence of pneumonia when compatible clinical findings are present
  • Direct samples of lower airway secretions may be obtained by a protected specimen brush (PSB), or bronchoalveolar lavage (BAL)
• PSB
  
  • Has a plug that protects the brush from contamination with upper airway secretions
  • After insertion into the lower airway area of interest, the plug is expelled, and a sterile brush is placed into the lung
  • The brush is cultured for bacteria quantitatively, and recovery of >103 colony forming units of bacteria/ml is considered evidence for pneumonia
• BAL
  
  • Involves washing a segment of the lung with sterile saline; collection of the instilled saline is cultured quantitatively, and recovery of >104 colony forming units of bacteria/ml of fluid is considered evidence for pneumonia
• Problems with this approach
  
  • The possibility of sampling error (only one segment of the lung is typically sampled, allowing for an area of pneumonia to be missed)
  • The cost and risks of bronchoscopy
  • Samples should be obtained prior to the initiation of antibiotics, because the sensitivity for isolation of bacteria is markedly decreased if the patient has just started antibiotics.
• Cultures of blood and pleural fluid
  
  • Should be obtained, as with community-acquired pneumonia
  • Since in the absence of an alternative site of infection, isolation of an organism will support that a pulmonary infiltrate is infectious and guide antibiotic selection

Question 26

Therapy:
Community-acquired penumonia (CAP):
Assessment of severity and initial triage

• The issue of whether a patient with pneumonia may be treated as an outpatient or requires hospitalization for intravenous antibiotics may be addressed by using…
• The prediction rule seeks to identify patients with…
• Patients are placed into one of five categories that are stratified for…
• Class I
• Classes II to V
• Patients that should be considered for outpatient therapy
• Patients that should be hospitalized

Answer 26

• The issue of whether a patient with pneumonia may be treated as an outpatient or requires hospitalization for intravenous antibiotics may be addressed by using…
  
  • A prediction rule based on demographic data from the pneumonia Patient Outcomes Research Team (PORT) or by using risk factors identified in the ATS Guidelines
• The prediction rule seeks to identify patients with…
  
  • Low risk of mortality who can be safely treated as outpatients
• Patients are placed into one of five categories that are stratified for…
  
  • Mortality and other adverse outcomes, such as need for ICU admission
• Class I
  
  • An expected mortality of 0.1%
  • Age <50
  • No comorbidities
  • No clinical instability
• Classes II to V
  
  • Mortalities ranging from 0.6 to 27%
  • Determined using a point system based on age and gender, co-existing illness, physical findings, laboratory studies, and chest x-ray findings
• Patients that should be considered for outpatient therapy
  
  • Low risk categories (I or II)
• Patients that should be hospitalized
  
  • Higher risk groups (IV and V)

Question 27

Therapy:
Community-acquired penumonia (CAP):
Antibiotic therapy

• Empiric antibiotic therapy for CAP needs to cover…
• Penicillin
• Resistance for penicillin
• Resistance for “atypical organisms”
• Resistance of Streptococcus pneumoniae to antibiotics

Answer 27

• Empiric antibiotic therapy for CAP needs to cover…
  
  • Both Streptococcus pneumoniae and “atypical” organisms
  • Coverage of Streptococcus pneumoniae is made more difficult by resistance of this pathogen to a number of antibiotic classes
• Penicillin
  
  • Therapy of choice for Streptococcus pneumoniae for many years
• Resistance for penicillin
  
  • Increasing PCN and cephalosporin resistance is mediated by Penicillin Binding Proteins ( PBP) and cannot be overcome with B-lactamase inhibitors (such as clavulanate, sulbactam, tazobactam)
  • Resistance has also been noted to other antibiotics such as macrolides and most recently the quinolones
• Resistance for “atypical organisms”
  
  • Acquired resistance is not an important issue for the “atypical” organisms
  • These organisms are intrinsically resistant to beta-lactam antibiotics (for example, penicillin or cephalosporins)
  • The only drug classes active against these organisms are the tetracyclines, macrolides and quinolones
• Resistance of Streptococcus pneumoniae to antibiotics
  
  • Predicted by recent receipt of that particular class of antibiotics
  • Ex. recent use of a quinolone antibiotic should dictate that empiric antibiotic therapy should be with a regimen other than a quinolone
  • The extent of antibiotic resistance in Streptococcus pneumoniae is greatest with macrolide antibiotics
    
    • Therefore, macrolides are generally combined with a beta-lactam antibiotic

Question 28

Therapy:
Community-acquired penumonia (CAP):
Antibiotic therapy

• Treatment for CAP will be received as an outpatient
  
  • Previously healthy patients
  • Patients with comorbidities
• Treatment for CAP will be received as an inpatient
  
  • Treatment on a medical ward
  • Treatment in ICU
    
    • Pseudomonas is not an issue
    • Pseudomonas is an issue

Answer 28

• Treatment for CAP will be received as an outpatient
  
  • Previously healthy patients
    
    • Azithromycin or doxycycline
  • Patients with comorbidities
    
    • Azithromycin or quinolone
• Treatment for CAP will be received as an inpatient
  
  • Treatment on a medical ward
    
    • Azithromycin plus beta-lactam
  • Treatment in ICU
    
    • Pseudomonas is not an issue
      
      • Macrolide plus beta-lactam
    • Pseudomonas is an issue
      
      • Antipseudomonal beta-lactam plus quinolone

Question 29

Therapy:
Community-acquired penumonia (CAP):
Assessment of Response, Duration of Therapy, and Conversion to Oral Therapy

• The only means to assess appropriateness of antibiotics
• Clinical improvement in patients on adequate therapy
• Median time for stabilization of vital signs and resolution of fever
  
  • In hospitalized patients with CAP
  • In patients with severe CAP
• Current recommendation for initial antibioitc treatment
• Chest x-ray abnormalities

Answer 29

• The only means to assess appropriateness of antibiotics
  
  • Clinical criteria, because therapy of CAP is often empirical
• Clinical improvement in patients on adequate therapy
  
  • Occurs within the first few days of therapy
  • Patients who are destined to deteriorate typically do so in the first 48 hours
• Median time for stabilization of vital signs and resolution of fever
  
  • In hospitalized patients with CAP
    
    • 3 days
  • In patients with severe CAP
    
    • May have continued fevers for up to a week or more
    • Clinical response is delayed
• Current recommendation for initial antibioitc treatment
  
  • Since clinical response often does not occur for several days, initial antibiotic regimen should not be altered in the first 3 days of therapy unless culture data indicates a more appropriate antibiotic choice or the patient deteriorates significantly
• Chest x-ray abnormalities
  
  • May not clear for up to six weeks after appropriate therapy is initiated
  • May worsen initially, even in patients on appropriate antibiotics
  • Repetition of chest x-rays is not indicated unless the patient fails to improve or has evidence for complications, such as empyema

Question 30

Therapy:
Community-acquired penumonia (CAP):
Assessment of Response, Duration of Therapy, and Conversion to Oral Therapy

• Intravenous therapy
• Drug levels in the lung
• The newer quinolones
• The macrolide azithromycin
• These considerations, combined with clinical observations, have led to early conversion from…
• Most authorities now recommend that hospitalized patients be converted to…
• Early conversion

Answer 30

• Intravenous therapy
  
  • Continued until normalization of vital signs and resolution of symptoms
• Drug levels in the lung
  
  • Bactericidal, despite the lower serum levels achieved with oral antibiotics
• The newer quinolones
  
  • Have nearly 100% bioavailability, giving comparable serum levels by oral and intravenous administration
• The macrolide azithromycin
  
  • Has a half-life approaching 14 hours, providing high tissue levels long after the drug is administered
• These considerations, combined with clinical observations, have led to early conversion from…
  
  • Intravenous to oral antibiotics that have comparable spectra of activity
• Most authorities now recommend that hospitalized patients be converted to…
  
  • Oral therapy when fever abates and the patient is clinically stable
• Early conversion
  
  • Allows for early hospital discharge and significant health care cost savings
  • Supports the practice of limiting intravenous antibiotics to the period of clinical instability

Question 31

Therapy:
Hospital-acquired pneumonia (HAP)

• Hospital-acquired organisms
• Example empiric regimens: antibiotics and rationale for each
  
  • Early-onset VAP
  • Late-onset VAP
  • HAP, non-VAP
• When diagnostic studies identify a pathogen, antibiotic therapy is subsequently…

Answer 31

• Hospital-acquired organisms
  
  • Frequently antibiotic resistant
  • May mandate use of multiple antibiotics
  • The risk of resistance rises as the duration of hospitalization increases, and the use of prior antibiotics increases
  • The risk of multiresistant organisms is much higher for late-onset VAP than early-onset VAP
• Example empiric regimens
  
  • Early-onset VAP
    
    • Antibiotics: Ampicillin/sulbactam
    • Rationale: Covers S. pneumoniae, H. influenzae, S. aureus
  • Late-onset VAP
    
    • Antibiotics: Vancomycin, cefepime, tobramycin
    • Rationale: Covers MRSA, Pseudomonas and other Gram negative rods
  • HAP, non-VAP
    
    • Antibiotics: Piperacillin/tazobactam
    • Rationale: Covers aerobic and anaerobic Gram negative rods
• When diagnostic studies identify a pathogen, antibiotic therapy is subsequently…
  
  • Nnarrowed to target the pathogen(s) involved and its particular susceptibility profile

Question 32

Therapy:
Hospital-acquired pneumonia (HAP):
Failure of empiric therapy

• Several possible reasons for patients to fail empiric therapy
  
  • The empiric antibiotics
  • The pneumonia
  • The diagnosis
• What should prompt investiation into alternative pathogens

Answer 32

• Several possible reasons for patients to fail empiric therapy
  
  • The empiric antibiotics may not have activity against the pathogen causing pneumonia
    
    • Ex. Pseudomonas aeruginosa may rarely cause community acquired pneumonia, hence the empiric use of a macrolide, cephalosporin, and/or fluoroquinolone may not provide anti-microbial activity
  • The pneumonia may be caused by an unusual pathogen, such as…
    
    • Mycobacterium tuberculosis
    • A fungus (Blastomycosis, Histoplasmosis, Coccidiomycosis, or Aspergillus)
    • A virus that is not treated with any anti-bacterial antibiotics.
  • The diagnosis may be incorrect
    
    • Ex. pulmonary embolism or Wegener’s granulomatosis as the cause of fever and a pulmonary infiltrate
• What should prompt investiation into alternative pathogens
  
  • Failure to show signs of improvement with empiric therapy

Question 33

Which of the following is true with respect to CAP:

• A. More than 50% of patients with CAP require admission to hospital
• B. Treatment of CAP with ceftriaxone is logical because it provides coverage of pneumococci and atypicals
• C. Knowledge of the prior antibiotic treatment of a patient with CAP is important because it will modify the empiric regimen chosen
• D. Coverage of MRSA and Pseudomonas are important in all cases of CAP

Question 34

With respect to VAP, which of the following is true:

• A. Since patients with VAP are in the ICU, multidrug resistance is uncommon
• B. Antibiotic treatment for VAP can wait until the susceptibilities of the infecting organisms are known
• C. VAP is caused by aspiration rather than inhalation
• D. Pneumocystis carinii should always be covered in an antibiotic regimen for VAP