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					        1004 Journal meeting
               報告人: 王又德醫師
              指導醫師: 陳志金主任



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An update on Legionella
Jordi Carratala and Carolina Garcia-Vidal

Curr Opin Infect Dis. 2010 Apr;23(2):152-7
                Introduction
• Legionella pneumophila has been increasing in
   a. Community-acquired pneumonia (CAP)
   b. Nosocomial acquired pneumonia
• Health / Immuno-suppressed hosts
• The majority of cases of Legionnaires’ disease are
  caused by L. pneumophila serogroup 1
               Epidemiology
• A total of 23076 cases of legionellosis reported to the
   CDC through the National Notifiable Disease
   Surveillance System (1990-2005)
 analyzed to determine epidemiologic trends
a. Age : 45-64 years
b. Male predominant
c. Area : Eastern of United states
d. Season : Summer / Fall
              Epidemiology
• European Working Group for Legionella Infections (EWGLI)
 - 8.2 cases per million population (2003-2004)
• German multicenter study of the Community-Acquired
   Pneumonia Competence Network (CAPNETZ)
 - Ambulatory and hospitalized patients (3.7 and 3.8%)
 - Ambulatory patients with Legionella pneumonia
   a. Equal sex distribution
   b. Younger
   c. Less comorbidity
   d. a milder clinical course without fatalities
               Epidemiology
• low-risk patients with CAP conducted in Spain
  (pneumonia severity index < 90 points)
   L. pneumophila – 2nd most frequent
               Pathogenesis
• Contaminated aerosols produced by water systems such as
  cooling towers, showers, hot water distribution systems
• Aspiration and direct instillation into the lung
• Against high levels of chlorine by the formation of biofilms
            Clinical diagnosis
• Fiumefreddo et al.
  - 82 consecutive ptaients with Legionella CAP
    368 consecutive patients with non-Legionella CAP
 Independent predictors of Legionella pneumonia
  a. High body temperature
  b. absence of sputum production
  c. low serum sodium concentration
  d. high levels of lactate dehydrogenase and CRP
  e. low platelet counts.
             Clinical diagnosis
• Diagnostic score for Legionella CAP.
  a. 191 patients (42%) with a score of 0 or 1 point - 3%
  b. 73 patients (16%) with at least 4 points, 66% of
     patients had Legionella CAP.
             Clinical diagnosis
• CBPIS score -
  Positive - male sex
              previous receipt of beta-lactam therapy
              temperature >39C
  Negative - purulent sputum
               pleuritic chest pain
               previous upper respiratory tract infection
• Roso´n et al
  Legionella pneumonia was independently associated
  with early treatment failure
Legionellosis in immunosuppressed patients
• Immunosuppression –
  a. some forms of cancer
  b. organ transplantation
  c. Corticosteroids administration
  d. treatment with tumor necrosis factor-a (TNFa) antagonists
   risk factors for Legionnaires’ disease
Legionellosis in immunosuppressed patients
 • Jacobson et al
 - 49 cancer patients with a positive Legionella culture or
   direct fluorescent antibody (DFA) (1991–2003)
   a. 82% hematologic malignancy
   b. 37% were bone marrow transplant recipients
   c. Lymphopenia (47%)
   d. systemic corticosteroids (41%)
   e. chemotherapy (63%)
Legionellosis in immunosuppressed patients
 49 patients results
 • multilobar (61%) / bilateral (55%) pulmonary involve
 • Response to therapy was 8 days
 • 37 % prolonged duration of treatment (mean 25 days)
 • Fatality rate was 31%.
 • Two patients had relapse
  Prolong course by a newer macrolide or quinolone
Legionellosis in immunosuppressed patients
• Gudiol et al
• Outbreak of Legionnaires’ disease
  4-week period among severely immunosupressed patients
  hospitalized at a cancer center.
• Ten of the 12 patients involved in the outbreak presented
  with pneumonia.
• L. pneumophila serogroup 1 was isolated from five sputum
  samples and from the water system supply.
• Attributable case fatality rate was 8.3%
Legionellosis in immunosuppressed patients
 • Solid organ transplant (SOT) recipients
 - immunosuppressive therapy related deficiencies in
   cellular immune function.
 • 14 cases (0.5%) of Legionnaires’ disease occurring in
    2946 SOT recipients (1985 to 2007)
 • L. pneumophila serogroup 1 was the species involved
 • High fever, chills, cough, and multilobar pneumonia
 • 8 pts by culture, and 6 pts by urinary antigen test
 • Erythromycin / levofloxacin
 • Fatality rate was 14.3%.
Legionellosis in immunosuppressed patients
 • Patients treated with TNFa antagonists in France
   - Relative risk between 16.5 and 21.0
      Microbiological diagnosis
• Definitive diagnosis of legionellosis
- Culture from respiratory secretions or pleural fluid
   on buffered charcoal yeast extract (BCYE) agar
• DFA staining is not sensitive (<60%)
• Serology -
  - four-fold rise in antibody titers to at least 1 : 128 in
    acute and convalescent sera.
      Microbiological diagnosis
• Legionella urinary antigen – inexpensive rapid test
  (serogroup 1)
• Sensitivity : 0.74 (0.68–0.81)
• Specificity : 0.991 (0.984–0.997)
• Urine antigen testing and sputum culture
   the best diagnostic combination
• DNA amplification by PCR  more expensive
            Antibiotic therapy
• Reduction in case fatality rates
• Azithromycin and fluoroquinolones / erythromycin
   inhibit intracellular growth of L. pneumophila
• Levofloxacin versus older macrolides
  a. Faster resolution of pneumonia symptoms
  b. Rapid achievement of clinical stability
  c. Shorter length of hospital stay
  (none of the studies were randomized trials)
            Antibiotic therapy
• Combined therapy - in mostly severe unresponsive
  - No convincing evidence
  - Risk additional toxicity and drug interactions
  - Rifampin to levofloxacin or clarithromycin
     no additional benefit
  - Azithromycin with fluoroquinolones is scarce
            Antibiotic therapy
• levofloxacin (or other fluoroquinolone such as
  moxifloxacin) or azithromycin
   Drugs of choice for Legionella pneumonia.
• Duration - 7–10 days
           - 21 day in severely immunosuppressed pts
                   Conclusion
• Routine use of Legionella testing for all patients with
  pneumonia is recommended.
• Urinary antigen test - valuable tool for rapid diagnosis
• Azithromycin and fluoroquinolones is superior to older
  macrolides
• Combine therapy is not suggested.
• Pay attention to immuno-compromised patient
THANKS

				
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