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Definition
 Community-acquired pneumonia (CAP) is
  defined as an acute infection of the lung
  parenchyma accompanied by symptoms of
  acute illness, which is not acquired in
  hospitals or other long-term care facilities.
                      -Clin. infect Dis. 2000;31:347-82
Community-acquired Pneumonia
   Epidemiology & Terminology
   Microbiology
   Exposure & Relevant Hx
   Diagnosis
   Prognosis
   Treatment
   Prevention
Alphabet Soup for Pneumonia
 HAP: Hospital-acquired pneumonia
   ≥ 48 h from admission

 VAP: Ventilator-associated pneumonia
   ≥ 48 h from endotracheal intubation

 HCAP: Healthcare-associated pneumonia
   Long-term care facility (NH), hemodialysis, outpatient
    chemo, wound care, etc.

 CAP: Community-acquired pneumonia
   Outside of hospital
Epidemiology
 8th leading cause of
  death in US in 2007
 4-5 million cases per
  year in US
    25% require
     hospitalization
    Almost 916,000 cases
     annually in pts >65 yo
 Case fatality rate has
  not changed
  substantially since
  penicillin                         www.cdc.gov/mmwr


                  cdc.gov/nchs/data/hestat
Microbiology
 Causative organism established in 60% CAP in
  research setting, 20% in clinical setting
 “Typical”:
   S. pneumoniae, Haemophilus influenzae,
    Staphylococcus aureus, Group A streptococci, Moraxella
    catarrhalis, anaerobes, and aerobic gram-negative
    bacteria
 “Atypical” - 20-28% CAP worldwide
   Legionella spp, Mycoplasma pneumoniae,
    Chlamydophila (formerly Chlamydia) pneumoniae, and
    C. psittaci
   Mainly distinguished from typical by not being detectable
    on Gram stain or cultivable on standard media
Microbiology of CAP among
hospitalized patients
Outpatient         Streptococcus pneumoniae
                   Mycoplasma pneumoniae
                   Haemophilus influenzae
                   Chlamydophila pneumoniae
                   Respiratory viruses

Inpatient (Ward)   S. pneumoniae
                   M. pneumoniae
                   H. influenzae
                   C. Pneumoniae
                   Legionella species
                   Respiratory viruses
                   Aspiration


Inpatient (ICU)    S. pneumoniae
                   Legionella spp.
                   Staphylococcus aureus
                   Gram-negative bacilli
Age-specific
Rates of
Hospital
Admission by
Pathogen




    Marsten. Community-based pneumonia incidence study group.
                Arch Intern Med 1997;157:1709-18
Typical vs
Atypical CAP

 CXR patterns
     Bronchopneumonia: 88%
      C. pneumo vs 77%
      Pneumococcal, P=0.67
     Lobar or air-space: 29%
      C. pneumo vs 54%
      Pneumococcal




Kauppinen et al. Arch Intern Med 1996; 156: 1851.
Comorbidities & Associated
Pathogens
Alcoholism       Strep pneumoniae
                 Oral anaerobes
                 Klebsiella pneumoniae
                 Acinetobacter spp
                 M. tuberculosis

COPD and/or      Haemophilus influenzae
Tobacco          Pseudomonas aeruginosa
                 Legionella spp
                 S. pneumoniae
                 Moraxella catarrhalis
                 Chlamydophila pneumoniae
Aspiration         Gram-negative enteric pathogens
                   Oral anaerobes

Lung Abscess         CA-MRSA
                     Oral anaerobes
                     Endemic fungi
                     M. tuberculosis
                     Atypical mycobacteria

Structural lung    P. aeruginosa
disease (e.g.      Burkholderia cepacia
bronchiectasis)    S. aureus

Advanced HIV         Pneumocystis jirovecii
                     Cryptococcus
                     Histoplasma
                     Aspergillus
                     P. aeruginosa
Zoonotic Exposures & Associated
Pathogens
 Bat or bird        Histoplasma capsulatum
 droppings
 Birds              Chalmydophila psittaci
                    Poultry: avian influenza

 Rabbits            Francisella tularensis
 Farm animals or    Coxiella burnetti (Q fever)
 parturient cats
Exposures & Associated Pathogens
Hotel or cruise ship             Legionella spp


Travel or residence in US        Coccidioides spp
                                 Hantavirus

Travel or residence in Asia        Burkolderia pseudomallei
                                   Staph aureus
                                   H.influenzae
                                   Avian influenza A (H5N1)
Influenza active in community      Influenza
                                   S. pneumonae
                                   Staph aureus (MRSA)
                                   H. influenzae
Cough >2 wks with whoop or       Bordetella pertussis
posttussive vomitting
Diagnosis: Cultures
 Pretx Blood Cultures
    Yield 5-15%
    Stronger indication for severe CAP
    Host factors: cirrhosis, asplenia, complement
     deficiencies, leukopenia
 Pretx expectorated sputum Gs & Cx
    Yield can be variable
    Depends on multiple factors: specimen collection,
     transport, speed of processing, use of cytologic criteria
    Predominant morphotype seen in only 14% of 1669
     hospitalized CAP pts (Garcia-Vasquez, Arch Intern Med
     2004)
 Pretx endotracheal aspirate Gs & Cx
 Pleural effusions >5 cm on lateral upright CXR
Diagnosis: Other testing
 Urinary antigen tests
   S. pneumoniae & L.
    pneumophila
    serogroup 1
   50-80% sensitive,
    >90% specific in adults
   Pros: rapid (15 min),
    simple, can detect
    Pneumococcus after
    abx started
   Cons: cost, no
    susceptibility data, not
    helpful in patients with
    recent CAP (prior 3
    months)
Diagnosis: Other testing
 Acute-phase serologies
    C. pneumoniae, Mycoplasma, Legionella spp
    Not practical given slow turnaround & single acute-phase
     result unreliable
 Influenza testing
    Hospitalized patients: Severe respiratory illness (T> 37.8°C
     with SOB, hypoxia, or radiographic evidence of pneumonia)
     without other explanation and suggestive of infectious
     etiology should get screened during season
    NP swab or nasal wash/aspirate
    Rapid flu test (15 min)
      Distinguishes A vs B
      Sensitivity 50-70%; specificity >90%
    Respiratory virus DFA & culture - reflex subtyping for A
    Respiratory viral PCR panel - reflex subtyping for A
    Influenza A PCR panel
How to obtain a nasopharyngeal
swab
2009-2010 Influenza Surveillance
  Seattle - King County




www.kingcounty.gov/healthservices/health/communicable/immunization/fluactivity.aspx
To Admit or Not?
Pneumonia Severity & Deciding Site of Care
 Using objective criteria to risk stratify & assist
  in decision re outpatient vs inpatient
  management
 PSI
 CURB-65
 Caveats
    Other reasons to admit apart from risk of death
    Not validated for ward vs ICU
    Labs/vitals dynamic
Pneumonia Severity Index
PORT study    Fine, N Engl J Med 1997;336:243.
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                                Site-of-Care Decisions

  •      Hospital admission decision
         - Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia,
         respiratory rate, low blood pressure, age 65 years or greater), or prognostic models,
         such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP
         who may be candidates for outpatient treatment (Strong recommendation; Level I
         evidence)

         - Objective criteria or scores should always be supplemented with physician
         determination of subjective factors, including the ability to safely and reliably take
         oral medication and the availability of outpatient support resources (Strong
         recommendation; Level II evidence)

         - For patients with CURB-65 scores ≥ 2, more-intensive treatement – that is,
         hospitalization or, where appropriate and available, intensive in-home health care
         services – is usually warranted (Moderate recommendation; Level III evidence)

Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                                Site-of-Care Decisions

  •      ICU admission decision
         - Direct admission to an ICU is required for patients with septic shock requiring
         vasopressors or with acute respiratory failure requiring intubation and mechanical
         ventilation (Strong recommmendation; Level II evidence)

         - Direct admission to an ICU or high-level monitoring unit is recommended for
         patients with 3 of the minor criteria for severe CAP listed in table 4 (Moderate
         recommendation; Level II evidence)




Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Criteria for Severe CAP
 Minor criteria
    Respiratory rate ≥30 breaths/min
    PaO2/FiO2 ratio ≥ 250
    Multilobar infiltrates
    Confusion/disorientation
    Uremia (BUN ≥20 mg/dL)
    Leukopenia (WBC <4000 cells/mm3)
    Thrombocytopenia (platelets <100,000 cells/mm3)
    Hypothermia (core T <36°C)
    Hypotension requiring aggressive fluid resuscitation
 Major criteria
    Invasive mechanical ventilation
    Septic shock with the need for vasopressors
Consensus Guidelines on the Management of Community-Acquired
 Pneumonia
   Table 5: Clinical Indications for More Extensive Diagnostic Testing
   Indication                     Blood culture             Sputum culture             Legionella UAT        Pneumococcal UAT   Other
   Intensive care unit                  X                          X                          X                     X            Xa
   admission

   Failure of outpatient                                           X                          X                     X
   antibiotic therapy

   Cavitary infiltrates                 X                          X                                                             Xb
   Leukopenia                           X                                                                           X
   Active alcohol abuse                 X                          X                          X                     X
   Chronic severe liver                 X                                                                           X
   disease

   Severe                                                          X
   obstructive/structural
   lung disease

   Asplenia (anatomic or                X                                                                           X
   functional

   Recent travel (within                                                                      X                                  Xc
   past 2 weeks)

   Positive Legionella UAT                                        Xd                         NA
   result

   Positive pneumococcal                X                          X                                               NA
   UAT result

   NOTE. NA, not
   Pleural effusionapplication; UAT urinaryXantigen test             X                        X                     X            Xe
   a Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage.
   b Fungal and tuberculosis cultures.
   c See table 8 for details
   d Special media for Legionella
   e Thoracentesis and pleural fluid cultures

Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Outpatient Empiric CAP Abx
 Healthy; no abx x past 3 months
    Macrolide e.g. azithromycin
    2nd choice: doxycycline
 Comorbidities; abx x past 3 mon (use alternative
  abx)
    Respiratory fluoroquinolone: Moxifloxacin, levofloxacin
     750 mg, gemifloxacin
    Beta-lactam + macrolide

 Regions with >25% high-level macrolide-resistant
  S. pneumo, consider alternative agents
         2007 IDSA/ATS Guidelines for CAP in Adults.
Inpatient Empiric CAP Abx
 Inpatients in ward
    Respiratory fluoroquinolone
    ß-lactam + macrolide
 Inpatients in ICU
    ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) +
     macrolide
    Respiratory fluoroquinolone for PCN-allergic pts
 Pseudomonas
    Anti-pneumococcal & anti-pseudomonal ß-lactam +
     azithromycin + cipro/levofloxacin
    Can substitute quinolone for aminoglycoside
    PCN-allergic: can substitute aztreonam
 CA-MRSA: Add vanco or linezolid

          2007 IDSA/ATS Guidelines for CAP in Adults.
Influenza pneumonia
Some things to keep in mind…
 Antiviral treatment within 48 hrs
   Reduce likelihood of lower tract complications
    & antibacterial use in outpatients
   Impact on hospitalized pts less clear
 Possible exceptions to <48 h rule:
   Immunocompromised patients
   To reduce viral shedding for infection control in
    hospitalized patients
Influenza pneumonia
Some things to keep in mind…
 Influenza B
   Oseltamavir 75 mg PO BID x 5 days
   Zanamavir 2 INH BID x 5 days
 Influenza A
   H3N2 - general seasonal
     Resistant to adamantane antivirals
   H1N1 - general seasonal
     High rate of oseltamavir resistance in 2008-2009
     Still susceptible to zanamavir
   Novel H1N1 (Swine flu)
     Sensitive to neuraminidase inhibitors
     Resistant to adamantanes
Drug-resistant Strep pneumoniae
ß-lactam resistance
 Risk factors
      Age >65 yrs
      ß-lactam x previous 3 mon
      Medical comorbidities
      Exposure to child in day care
 Current levels of ß-lactam resistance do not
  generally result in treatment failure with
  amoxicillin, ceftriaxone or cefotaxime
    As opposed to macrolide or fluoroquinolone resistance
 Clinically relevant threshold - MIC 4?
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                                 Time to First Antibiotic Dose




  •      For patients admitted through the emergency department (ED),
         the first antibiotic dose should be administered while still in the ED
         (Moderate recommendation; Level III evidence)




Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                     Switch from Intravenous to Oral Therapy


  •      Patients should be switched from intravenous to oral therapy
         when they are hemodynamically stable and improving
         clinically, are able to ingest medications, and have a normally
         functioning gastrointestinal tract (Strong recommendation;
         Level II evidence)

  •      Patients should be discharged as soon as they are clinically
         stable, have no other active medical problems, and have a safe
         environment for continued care. Inpatient observation while
         receiving oral therapy is not necessary (Moderate
         recommendation; Level II evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                               Duration of Antibiotic Therapy



  •      Patients with CAP should be treated for a minimum of 5 days (Level I
         evidence), should be afebrile for 48-72 h, and should have no more than one
         CAP-associated sign of clinical instability (Table 10) before discontinuation
         of therapy (Moderate recommendation; Level II evidence)

  •      A longer duration of therapy may be needed if initial therapy was not active
         against the identified pathogen or if it was complicated by extrapulmonary
         infection, such as meningitis or endocarditis (Weak recommendation ; Level III
         evidence)




Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
   Table 10. Criteria for clinical stability
   Temperature ≤ 37.8oC
   Heart rate ≤ 100 beats/min
   Respiratory rate ≤ 24 breaths/min
   Systolic blood pressure ≥ 90 mmHg
   Arterial oxygen saturation ≥ 90% or pO2 ≥ 60 mmHg on room air
   Ability to maintain oral intakea
   Normal mental statusa




   NOTE. Critera are from [268, 274, 294]. pO2 oxygen partial pressure.
   a
     Important for discharge or oral switch decision but not necessarily for determination of nonresponse


Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                            Other Treatment Considerations I
  •      Patients with CAP who have persistent septic shock despite
         adequate fluid resuscitation should be considered for treatment
         with drotrecogin alfa activated within 24h of admission (Weak
         recommendation; Level II evidence)

  •      Hypotensive, fluid-resuscitated patients with severe CAP should
         be screened for occult adrenal insufficiency (Moderate
         recommendation; Level II evidence)




Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                            Other Treatment Considerations II
  •      Patients with hypoxemia or respiratory distress should receive a
         cautious trial of noninvasive ventilation unless they require
         immediate intubation because of severe hypoxemia (PaO2/FiO2
         ratio, <150) and bilateral alveolar infiltrates (Moderate
         recommendation; Level I evidence)

  •      Low-tidal-volume ventilation (6 cm3/kg of ideal body weight)
         should be used for patients undergoing ventilation who have
         diffuse bilateral pneumonia or acute respiratory distress
         syndrome (Strong recommendation; Level I evidence)


Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
   Table 11. Patterns and Etiologies of Types of Failure to Respond
   Failure to Improve
   Early (<72h of treatment)
       • Normal response
   Delayed
         •   Resistant microorganism
              - Uncovered pathogen
              - Inappropriate by sensitivity
         •    Paraneumonic effusion/empyema
         •    Nosocomial superinfection
               - Nosocomial pneumonia
               - Extrapulmonary
         •    Noninfectious
               - Complication of pneumonia (e.g., BOOP)
               - Misdiagnosis: PE, CHF, vasculitis
               - Drug fever



Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
                 Management of Non-responding Pneumonia
  • The use of systematic classification of possible
    causes of failure to respond, based on time of
    onset and type of failure (Table 11), is
    recommended. (Moderate recommendation;
    Level II evidence)




Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
 of Community-Acquired Pneumonia
   Table 11. Patterns and Etiologies of Types of Failure to Respond
   Deterioration or Progression
   Early (<72h of treatment)
         •    Severity of illness at presentation
         •    Resistant microorganism
                -   Uncovered pathogen
                -   Inappropriate by sensitivity
         •    Metastatic infection
                -   Empyema/parapneumonic
                -   Endocarditis, meningitis, arthritis
         •    Inaccurate diagnosis
                -   PE, aspiration, ARDS
                -   Vasculitis (e.g. SLE)
   Delayed
        •  Nosocomial superinfection
             -   Nosocomial pneumonia
             -   Extrapulmonary
        •  Exacerbation of comorbid illness
        •  Intercurrent noninfectious disease
             -   PE
             -   Myocardial infarction
             -   Renal failure


Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management
  of Community-Acquired Pneumonia
    Table 12 Factors Associated with Non-responding Pneumonia
                                                       Overall Failure a                                          Early failure b
    Risk Factor                   Decreased Risk                 Increased Risk                Decreased Risk              Increased Risk
    Older Age(>65 years)          ...                            ...                           0.35                        ...
    COPD                          0.60                           ...                           ...                         ...
    Liver disease                 ...                            2.0                           ...                         ...
    Vaccination                   0.30                           ....                          ...                         ...
    Pleural effusion              ...                            2.7                           ...                         ...
    Multilobar infiltrates        ...                            2.1                           ...                         1.81
    Cavitation                    ...                            4.1                           ...                         …
    Leukopenia                    ...                            3.7                           ...                         ...
    PSI class                     ...                            1.3                           ...                         2.75
                                                                                                                           …

    Legionella pneumonia          ...                            ...                           ...                         2.71
    Gram-negative pneumonia       ...                            ...                           ...                         4.34

    Fluoroquinolone therapy       0.50                           ...                           ....                        ...

    Concordant therapy            ...                            ...                           0.61                        ...
    Discordant therapy            ...                            ....                          ...                         2.51

NOTE. Data are relative risk values. COPD, chronic obstructive pulmonary disease; PSI, Pneumonia Severity Index
a
  From [84]. b From [81].

Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
 Case-control study from Canada - review of fluoroquinolone
  (FLQ) use among Cx-proven TB cases.
 Of 148 isolates of M. TB, 3 were FLQ resistant.
 Patients who had received multiple FLQ prescriptions were more
  likely than patients who had received a single FLQ prescription to
  be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%;
  odds ratio, 11.4; P<.04)

           Long, Clin Infect Dis 2009. May 15; 48: 1355.
Follow-up Response
Expected improvement?
 Clinical improvement w/ effective abx: 48-72 hrs
 Fever can last 2-5 days with Pneumococcus,
  longer with other etiologies, esp Staph aureus
 CXR clearing
    If healthy & <50 yo, 60% have clear CXR x 4 wks
    If older, COPD, bacteremic, alcoholic, etc. only 25%
     with clear CXR x 4 wks
 Switch from IV to PO
    Hemodynamically stable, improving clinically
    Able to ingest meds with working GI tract
Question…
What is far & away the most common reason
  for non-response to antibiotics in CAP?

1.   Cavitation
2.   Pleural effusion
3.   Multilobar involvement
4.   Discordant antibiotic/etiology
5.   None of the above
Inadequate Response to Therapy
What to consider
 Consider S. aureus, virus, resistant organism, TB, endemic fungi,
  Pneumocystis
 More unusual pathogens, atypical mycobacteria, higher bacteria
  (Nocardia, actinomycetes), fungi
 Noninfectious illness:
       Lung neoplasms with bronchial obstruction
       Lymphoma
       Systemic autoimmune disorders
       PE w/ infarct, pulm edema, ARDS
 Consider other testing:
       Lower tract sampling (bronch)
       CT chest
       PE work-up?
       Serologic testing
       Open lung biopsy
Prevention
Tried & true…




        http://www2a.cdc.gov/eCards

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CAP Diagnosis & Treatment

  • 1.
  • 2. Definition  Community-acquired pneumonia (CAP) is defined as an acute infection of the lung parenchyma accompanied by symptoms of acute illness, which is not acquired in hospitals or other long-term care facilities. -Clin. infect Dis. 2000;31:347-82
  • 3. Community-acquired Pneumonia  Epidemiology & Terminology  Microbiology  Exposure & Relevant Hx  Diagnosis  Prognosis  Treatment  Prevention
  • 4. Alphabet Soup for Pneumonia  HAP: Hospital-acquired pneumonia  ≥ 48 h from admission  VAP: Ventilator-associated pneumonia  ≥ 48 h from endotracheal intubation  HCAP: Healthcare-associated pneumonia  Long-term care facility (NH), hemodialysis, outpatient chemo, wound care, etc.  CAP: Community-acquired pneumonia  Outside of hospital
  • 5. Epidemiology  8th leading cause of death in US in 2007  4-5 million cases per year in US  25% require hospitalization  Almost 916,000 cases annually in pts >65 yo  Case fatality rate has not changed substantially since penicillin www.cdc.gov/mmwr cdc.gov/nchs/data/hestat
  • 6. Microbiology  Causative organism established in 60% CAP in research setting, 20% in clinical setting  “Typical”:  S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria  “Atypical” - 20-28% CAP worldwide  Legionella spp, Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia) pneumoniae, and C. psittaci  Mainly distinguished from typical by not being detectable on Gram stain or cultivable on standard media
  • 7. Microbiology of CAP among hospitalized patients Outpatient Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses Inpatient (Ward) S. pneumoniae M. pneumoniae H. influenzae C. Pneumoniae Legionella species Respiratory viruses Aspiration Inpatient (ICU) S. pneumoniae Legionella spp. Staphylococcus aureus Gram-negative bacilli
  • 8. Age-specific Rates of Hospital Admission by Pathogen Marsten. Community-based pneumonia incidence study group. Arch Intern Med 1997;157:1709-18
  • 9. Typical vs Atypical CAP  CXR patterns  Bronchopneumonia: 88% C. pneumo vs 77% Pneumococcal, P=0.67  Lobar or air-space: 29% C. pneumo vs 54% Pneumococcal Kauppinen et al. Arch Intern Med 1996; 156: 1851.
  • 10. Comorbidities & Associated Pathogens Alcoholism  Strep pneumoniae  Oral anaerobes  Klebsiella pneumoniae  Acinetobacter spp  M. tuberculosis COPD and/or  Haemophilus influenzae Tobacco  Pseudomonas aeruginosa  Legionella spp  S. pneumoniae  Moraxella catarrhalis  Chlamydophila pneumoniae
  • 11. Aspiration  Gram-negative enteric pathogens  Oral anaerobes Lung Abscess  CA-MRSA  Oral anaerobes  Endemic fungi  M. tuberculosis  Atypical mycobacteria Structural lung  P. aeruginosa disease (e.g.  Burkholderia cepacia bronchiectasis)  S. aureus Advanced HIV  Pneumocystis jirovecii  Cryptococcus  Histoplasma  Aspergillus  P. aeruginosa
  • 12. Zoonotic Exposures & Associated Pathogens Bat or bird  Histoplasma capsulatum droppings Birds  Chalmydophila psittaci  Poultry: avian influenza Rabbits  Francisella tularensis Farm animals or  Coxiella burnetti (Q fever) parturient cats
  • 13. Exposures & Associated Pathogens Hotel or cruise ship  Legionella spp Travel or residence in US  Coccidioides spp  Hantavirus Travel or residence in Asia  Burkolderia pseudomallei  Staph aureus  H.influenzae  Avian influenza A (H5N1) Influenza active in community  Influenza  S. pneumonae  Staph aureus (MRSA)  H. influenzae Cough >2 wks with whoop or  Bordetella pertussis posttussive vomitting
  • 14. Diagnosis: Cultures  Pretx Blood Cultures  Yield 5-15%  Stronger indication for severe CAP  Host factors: cirrhosis, asplenia, complement deficiencies, leukopenia  Pretx expectorated sputum Gs & Cx  Yield can be variable  Depends on multiple factors: specimen collection, transport, speed of processing, use of cytologic criteria  Predominant morphotype seen in only 14% of 1669 hospitalized CAP pts (Garcia-Vasquez, Arch Intern Med 2004)  Pretx endotracheal aspirate Gs & Cx  Pleural effusions >5 cm on lateral upright CXR
  • 15. Diagnosis: Other testing  Urinary antigen tests  S. pneumoniae & L. pneumophila serogroup 1  50-80% sensitive, >90% specific in adults  Pros: rapid (15 min), simple, can detect Pneumococcus after abx started  Cons: cost, no susceptibility data, not helpful in patients with recent CAP (prior 3 months)
  • 16. Diagnosis: Other testing  Acute-phase serologies  C. pneumoniae, Mycoplasma, Legionella spp  Not practical given slow turnaround & single acute-phase result unreliable  Influenza testing  Hospitalized patients: Severe respiratory illness (T> 37.8°C with SOB, hypoxia, or radiographic evidence of pneumonia) without other explanation and suggestive of infectious etiology should get screened during season  NP swab or nasal wash/aspirate  Rapid flu test (15 min)  Distinguishes A vs B  Sensitivity 50-70%; specificity >90%  Respiratory virus DFA & culture - reflex subtyping for A  Respiratory viral PCR panel - reflex subtyping for A  Influenza A PCR panel
  • 17. How to obtain a nasopharyngeal swab
  • 18. 2009-2010 Influenza Surveillance Seattle - King County www.kingcounty.gov/healthservices/health/communicable/immunization/fluactivity.aspx
  • 19. To Admit or Not? Pneumonia Severity & Deciding Site of Care  Using objective criteria to risk stratify & assist in decision re outpatient vs inpatient management  PSI  CURB-65  Caveats  Other reasons to admit apart from risk of death  Not validated for ward vs ICU  Labs/vitals dynamic
  • 20. Pneumonia Severity Index PORT study Fine, N Engl J Med 1997;336:243.
  • 21. Consensus Guidelines on the Management of Community-Acquired Pneumonia Site-of-Care Decisions • Hospital admission decision - Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment (Strong recommendation; Level I evidence) - Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources (Strong recommendation; Level II evidence) - For patients with CURB-65 scores ≥ 2, more-intensive treatement – that is, hospitalization or, where appropriate and available, intensive in-home health care services – is usually warranted (Moderate recommendation; Level III evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 22. Consensus Guidelines on the Management of Community-Acquired Pneumonia Site-of-Care Decisions • ICU admission decision - Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation (Strong recommmendation; Level II evidence) - Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in table 4 (Moderate recommendation; Level II evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 23. Criteria for Severe CAP Minor criteria Respiratory rate ≥30 breaths/min PaO2/FiO2 ratio ≥ 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN ≥20 mg/dL) Leukopenia (WBC <4000 cells/mm3) Thrombocytopenia (platelets <100,000 cells/mm3) Hypothermia (core T <36°C) Hypotension requiring aggressive fluid resuscitation Major criteria Invasive mechanical ventilation Septic shock with the need for vasopressors
  • 24. Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 5: Clinical Indications for More Extensive Diagnostic Testing Indication Blood culture Sputum culture Legionella UAT Pneumococcal UAT Other Intensive care unit X X X X Xa admission Failure of outpatient X X X antibiotic therapy Cavitary infiltrates X X Xb Leukopenia X X Active alcohol abuse X X X X Chronic severe liver X X disease Severe X obstructive/structural lung disease Asplenia (anatomic or X X functional Recent travel (within X Xc past 2 weeks) Positive Legionella UAT Xd NA result Positive pneumococcal X X NA UAT result NOTE. NA, not Pleural effusionapplication; UAT urinaryXantigen test X X X Xe a Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage. b Fungal and tuberculosis cultures. c See table 8 for details d Special media for Legionella e Thoracentesis and pleural fluid cultures Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 25. Outpatient Empiric CAP Abx  Healthy; no abx x past 3 months  Macrolide e.g. azithromycin  2nd choice: doxycycline  Comorbidities; abx x past 3 mon (use alternative abx)  Respiratory fluoroquinolone: Moxifloxacin, levofloxacin 750 mg, gemifloxacin  Beta-lactam + macrolide  Regions with >25% high-level macrolide-resistant S. pneumo, consider alternative agents 2007 IDSA/ATS Guidelines for CAP in Adults.
  • 26. Inpatient Empiric CAP Abx  Inpatients in ward  Respiratory fluoroquinolone  ß-lactam + macrolide  Inpatients in ICU  ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) + macrolide  Respiratory fluoroquinolone for PCN-allergic pts  Pseudomonas  Anti-pneumococcal & anti-pseudomonal ß-lactam + azithromycin + cipro/levofloxacin  Can substitute quinolone for aminoglycoside  PCN-allergic: can substitute aztreonam  CA-MRSA: Add vanco or linezolid 2007 IDSA/ATS Guidelines for CAP in Adults.
  • 27. Influenza pneumonia Some things to keep in mind…  Antiviral treatment within 48 hrs  Reduce likelihood of lower tract complications & antibacterial use in outpatients  Impact on hospitalized pts less clear  Possible exceptions to <48 h rule:  Immunocompromised patients  To reduce viral shedding for infection control in hospitalized patients
  • 28. Influenza pneumonia Some things to keep in mind…  Influenza B  Oseltamavir 75 mg PO BID x 5 days  Zanamavir 2 INH BID x 5 days  Influenza A  H3N2 - general seasonal  Resistant to adamantane antivirals  H1N1 - general seasonal  High rate of oseltamavir resistance in 2008-2009  Still susceptible to zanamavir  Novel H1N1 (Swine flu)  Sensitive to neuraminidase inhibitors  Resistant to adamantanes
  • 29. Drug-resistant Strep pneumoniae ß-lactam resistance  Risk factors  Age >65 yrs  ß-lactam x previous 3 mon  Medical comorbidities  Exposure to child in day care  Current levels of ß-lactam resistance do not generally result in treatment failure with amoxicillin, ceftriaxone or cefotaxime  As opposed to macrolide or fluoroquinolone resistance  Clinically relevant threshold - MIC 4?
  • 30. Consensus Guidelines on the Management of Community-Acquired Pneumonia Time to First Antibiotic Dose • For patients admitted through the emergency department (ED), the first antibiotic dose should be administered while still in the ED (Moderate recommendation; Level III evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 31. Consensus Guidelines on the Management of Community-Acquired Pneumonia Switch from Intravenous to Oral Therapy • Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract (Strong recommendation; Level II evidence) • Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary (Moderate recommendation; Level II evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 32. Consensus Guidelines on the Management of Community-Acquired Pneumonia Duration of Antibiotic Therapy • Patients with CAP should be treated for a minimum of 5 days (Level I evidence), should be afebrile for 48-72 h, and should have no more than one CAP-associated sign of clinical instability (Table 10) before discontinuation of therapy (Moderate recommendation; Level II evidence) • A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection, such as meningitis or endocarditis (Weak recommendation ; Level III evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 33. Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 10. Criteria for clinical stability Temperature ≤ 37.8oC Heart rate ≤ 100 beats/min Respiratory rate ≤ 24 breaths/min Systolic blood pressure ≥ 90 mmHg Arterial oxygen saturation ≥ 90% or pO2 ≥ 60 mmHg on room air Ability to maintain oral intakea Normal mental statusa NOTE. Critera are from [268, 274, 294]. pO2 oxygen partial pressure. a Important for discharge or oral switch decision but not necessarily for determination of nonresponse Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 34. Consensus Guidelines on the Management of Community-Acquired Pneumonia Other Treatment Considerations I • Patients with CAP who have persistent septic shock despite adequate fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24h of admission (Weak recommendation; Level II evidence) • Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency (Moderate recommendation; Level II evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 35. Consensus Guidelines on the Management of Community-Acquired Pneumonia Other Treatment Considerations II • Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation unless they require immediate intubation because of severe hypoxemia (PaO2/FiO2 ratio, <150) and bilateral alveolar infiltrates (Moderate recommendation; Level I evidence) • Low-tidal-volume ventilation (6 cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome (Strong recommendation; Level I evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 36. Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 11. Patterns and Etiologies of Types of Failure to Respond Failure to Improve Early (<72h of treatment) • Normal response Delayed • Resistant microorganism - Uncovered pathogen - Inappropriate by sensitivity • Paraneumonic effusion/empyema • Nosocomial superinfection - Nosocomial pneumonia - Extrapulmonary • Noninfectious - Complication of pneumonia (e.g., BOOP) - Misdiagnosis: PE, CHF, vasculitis - Drug fever Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 37. Consensus Guidelines on the Management of Community-Acquired Pneumonia Management of Non-responding Pneumonia • The use of systematic classification of possible causes of failure to respond, based on time of onset and type of failure (Table 11), is recommended. (Moderate recommendation; Level II evidence) Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 38. Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 11. Patterns and Etiologies of Types of Failure to Respond Deterioration or Progression Early (<72h of treatment) • Severity of illness at presentation • Resistant microorganism - Uncovered pathogen - Inappropriate by sensitivity • Metastatic infection - Empyema/parapneumonic - Endocarditis, meningitis, arthritis • Inaccurate diagnosis - PE, aspiration, ARDS - Vasculitis (e.g. SLE) Delayed • Nosocomial superinfection - Nosocomial pneumonia - Extrapulmonary • Exacerbation of comorbid illness • Intercurrent noninfectious disease - PE - Myocardial infarction - Renal failure Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 39. Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 12 Factors Associated with Non-responding Pneumonia Overall Failure a Early failure b Risk Factor Decreased Risk Increased Risk Decreased Risk Increased Risk Older Age(>65 years) ... ... 0.35 ... COPD 0.60 ... ... ... Liver disease ... 2.0 ... ... Vaccination 0.30 .... ... ... Pleural effusion ... 2.7 ... ... Multilobar infiltrates ... 2.1 ... 1.81 Cavitation ... 4.1 ... … Leukopenia ... 3.7 ... ... PSI class ... 1.3 ... 2.75 … Legionella pneumonia ... ... ... 2.71 Gram-negative pneumonia ... ... ... 4.34 Fluoroquinolone therapy 0.50 ... .... ... Concordant therapy ... ... 0.61 ... Discordant therapy ... .... ... 2.51 NOTE. Data are relative risk values. COPD, chronic obstructive pulmonary disease; PSI, Pneumonia Severity Index a From [84]. b From [81]. Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
  • 40.  Case-control study from Canada - review of fluoroquinolone (FLQ) use among Cx-proven TB cases.  Of 148 isolates of M. TB, 3 were FLQ resistant.  Patients who had received multiple FLQ prescriptions were more likely than patients who had received a single FLQ prescription to be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%; odds ratio, 11.4; P<.04) Long, Clin Infect Dis 2009. May 15; 48: 1355.
  • 41. Follow-up Response Expected improvement?  Clinical improvement w/ effective abx: 48-72 hrs  Fever can last 2-5 days with Pneumococcus, longer with other etiologies, esp Staph aureus  CXR clearing  If healthy & <50 yo, 60% have clear CXR x 4 wks  If older, COPD, bacteremic, alcoholic, etc. only 25% with clear CXR x 4 wks  Switch from IV to PO  Hemodynamically stable, improving clinically  Able to ingest meds with working GI tract
  • 42. Question… What is far & away the most common reason for non-response to antibiotics in CAP? 1. Cavitation 2. Pleural effusion 3. Multilobar involvement 4. Discordant antibiotic/etiology 5. None of the above
  • 43. Inadequate Response to Therapy What to consider  Consider S. aureus, virus, resistant organism, TB, endemic fungi, Pneumocystis  More unusual pathogens, atypical mycobacteria, higher bacteria (Nocardia, actinomycetes), fungi  Noninfectious illness:  Lung neoplasms with bronchial obstruction  Lymphoma  Systemic autoimmune disorders  PE w/ infarct, pulm edema, ARDS  Consider other testing:  Lower tract sampling (bronch)  CT chest  PE work-up?  Serologic testing  Open lung biopsy
  • 44.
  • 45. Prevention Tried & true… http://www2a.cdc.gov/eCards

Hinweis der Redaktion

  1. Lab-confirmed isolates
  2. -- HMC 20% resistance, UWMC 30-40% resistance.