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Pneumonia in hospitalized
                 patients
                                Diagnostic Strategy

                   Dr. Mahen Kothalawala MBBS, Dip in Micro, MD, MPH(NZ),
                               Consultant Clinical Microbiologist
                                   Teaching Hospital Kandy
Offsite consultant for TH Kegalle, DGH Matale, BH Nawalapitiya and Sirimawo Bandaranayake Specialized Hospital for
                                                     Children
1.
Introduction
Pneumonia in Hospitalized patients




    CAP              HCAP                        HAP              VAP


In the first 48     In CAP with              Pneumonia         Pneumonia
hrs of hospital   recent contact             developing        developing
  admission         with health             after 48 to 72     after 48 of
                   care system                hrs after        intubation
                                              admission      1. Early onset
                                                             2. Late onset
2.
HAP/VAP Burden
Ventilator-associated pneumonia
             (VAP) burden
• Common in Critical Care Unit

• Estimated 8 to 20% of ICU patients

• Occur up to 27% of mechanically ventilated
  patients

• Pts intubated > 24hrs are 6 to 21 times more
  likely to develop VAP than those intubated
  <24hrs
Mortality
• Mortality rates
  – range from 20 to 50%

• Some studies >70% (when caused by Multi
  resistant organisms)
  – Attributable mortality → difficult to quantify – due
    to confounders
  – But, VAP ↑mortality of the underlying disease by
    about 30%
Morbidity of VAP
• Prolongs ICU stay,

• Prolongs mechanical ventilation, and

• ↑↑ costs of hospitalization
3. Hospital-Acquired and ICU
   Pneumonia - Diagnosis
HAP/VAP
• “There is no doubt that the diagnosis and
  management of VAP remains one of the most
  controversial and challenging topics in
  management of critically ill patients.”
          (Chan C, Chest 2005;127:425 )



• The diagnosis of hospital-acquired pneumonia
  is complex.
Diagnostic Testing for HAP/VAP
• Diagnostic tests are ordered for two
  purposes:
• To define
  – whether a patient has pneumonia
  – etiologic pathogen when pneumonia is present.
Diagnosis of HAP/VAP
• A. Clinical Strategy
   – A radiographic infiltrate, plus the presence of at least one of the
     three clinical data
   – Clinical pulmonary infection score (CPIS)
• B. Microbiological Strategy
   – Non-invasive Methods
       • Blood Cultures:
       • Sputum Samples and Tracheal Aspirates:
   – Invasive Sampling Methods
       • Protected Specimen Brush (PSB):
       • Bronchoalveolar Lavage (BAL):
• C. Usage of other inflammatory markers to support Δof
  HAP/VAP
   – CRP
   – Procalcitonin
   – sTREM 1
A. Clinical Strategy

(A1) A radiographic evidence of infiltrate, plus the
  presence of at least one of the three clinical data
   • new onset of fever,
   • purulent sputum,
   • leukocytosis


(A2) Clinical pulmonary infection score (CPIS)
A single clinical finding VS multiple
                 features
• Presence of radiographic infiltrate with
• one clinical feature
  – fever,
  – leucocytosis, or
  – change of secretions – increase in volume or
   purulent
• have high sensitivity but low specificity
  (especially for VAP).
• Combination may improve specificity
Comparison clinical criteria with PM
              findings
• Presence of chest infiltrates, plus two of three
  clinical criteria resulted
  – 69% sensitivity
  – 75% specificity


• Using three clinical variables → sensitivity
  declined

• One variable → decline in specificity.
A2. Clinical pulmonary infection score (CPIS)


• A Tool with 6 easily obtained variables
  – body temperature,
  – white blood cell count,
  – quantity and purulence of tracheal secretions,
  – chest radiograph,
  – oxygenation, and,
  – bacterial growth in lower respiratory tracheal
    secretions
Table 1. Clinical Pulmonary Infection Score (CPIS)
Total Day #0 = _________ Total Day #3 = _________

                     Score                                                                                       Score
                                               Day 0                                    Day 3
                                 Temperature, ºC                            Temperature, ºC
                             ³38.5º - 38.9º = 1 point                   38.5º - 38.9º = 1 point
                             ³39.0º - 36.0º = 2 points                  39.0º - 36.0º = 2 points
                                 Blood leucocytes, mm-3                     Blood leucocytes, mm-3
                             <4.000 or >11.000 = 1 point                <4.000 or >11.000=1 point
                             50% band forms = add 1 point               50% band forms = add 1 point
                             Tracheal secretions                            Tracheal secretions
                             Presence of non-purulent tracheal          Presence of non-purulent tracheal
                                   secretions = 1 point                       secretions = 1 point
                             Presence of purulent tracheal secretions   Presence of purulent tracheal
                                   = 2 points                                 secretions = 2 points
                                 Oxygenation: PaO2/FIO2                     Oxygenation: PaO2/FIO2
                             >240 or ARDS = 0 point                     >240 or ARDS = 0 point
                             < 240 and no ARDS = 2 points               < 240 and no ARDS = 2 points
                                 Pulmonary radiography                      Pulmonary radiography
                             No infiltrate = 0 point                    No infiltrate = 0 point
                             Diffuse or patchy infiltrate = 1 point     Diffuse or patchy infiltrate = 1 point
                             Localized infiltrate= 2 points             Localized infiltrate= 2 points
                                 Microbiological Data                       Microbiological Data
                             Pathogenic bacterial cultured in rare or   Pathogenic bacterial cultured in rare
                                   hight quantity or no growth = 0            or hight quantity or no growth =
                                   point                                      0 point
                             Pathogenic bacterial cultured in           Pathogenic bacterial cultured in
                                   moderate or heavy quantity = 1             moderate or heavy quantity = 1
                                   point                                      point
                             Same pathogenic bacterial seen             Same pathogenic bacterial
                                                                        seen on Gram stain = add 1
                             on Gram stain = add 1 point
                                                                        point
Clinical pulmonary infection score
                 (CPIS)
• Score ranges from 0 to 12
• > 6/12 would correlate well →
  microbiologically confirmed HAP.
• CPIS → used to select patients to treat safely
  with short-course antibiotic.
• Some have shown that the score may lack
  sensitivity and specificity to establish → ΔHAP
Pitfalls of CPIS
• Observers variability
• Microbiological results are often delayed (48hrs)
  / Not available always

• Practical Approach – Usage with modifications

• Modifications of CPIS
  – Use of Gram Stain where results available in one day
  – Eliminate the culture report and take same cut off
Clinical Features without CXR findings
– fever,
– leukocytosis,
– purulent sputum, and
– a positive culture of a sputum or tracheal aspirate
  → nosocomial tracheobronchitis
Nosocomial tracheo-bronchitis Vs
              HAP/VAP
• Former no mortality
• Can progress rarely to HAP/VAP
• Contribute for cost of antibiotics
B. Microbiological Strategy
• Aim – to identify the specific pathogen by
  culture
  – (B1) Non respiratory culture
     • Blood
     • Pleural fluid
  – (B2) Lower respiratory culture (From LRT)
     • Invasive Method
         – BAL
         – PSB
     • Non Invasive method
         – Tracheal secretions
Lower respiratory tract specimens
• Useful to confirm the diagnosis and

• Adjust antibiotic treatment if necessary
Non invasive Method
             Tracheal Aspirates:

• Gram stain and culture of TA- may provide
  relevant microbiological information,

• Interpret with caution - as they not distinguish
  colonization from distal infection/pneumonia.

• In intubated patients, as TA is obtained from
  deep of lung has higher diagnostic value
(B2)Invasive Samples

• lower airways can be easily accessed by
  fibreoptic flexible bronchoscopy.

• samples → obtained under direct vision

• Possible contamination is less
Protected Specimen Brush (PSB):
• Threshold to discriminate colonization and
  infection is 103 cfu/mL

• PSB → high sensitivity (>70%) and specificity
  (80-90%) for infection.

• Prior antibiotic Rx ↓detection sensitivity
Bronchoalveolar Lavage (BAL):
• Has appropriate Sensitivity and specificity to
  Δ HAP

• Cutoff >104 cfu/mL

• *> 2% of bacteria embedded in PMN or mφ
  cells in centrifuged BAL fluid → have a high
  specificity for infection (approaching 100%)

• Antibiotic treatment readily ↓ intracellular
  bacterial count.
Clinical Vs Microbiological
                      Strategies
The Clinical Approach                 Microbiological Approach
• Overly (too) sensitive              • Requires Invasive
• Patients treated with                 procedures to achieve
  antibiotics when a non-
  infectious process is                 acceptable sensitivity and
  responsible for the clinical          specificity
  findings. Such as
    –   congestive heart failure,     • Non invasive- Isolation false
    –   atelectasis,                    positive pathogens
    –   pulmonary thrombo embolism,
    –   pulmonary drug reactions,
                                      • Negative results- highly
    –   pulmonary hemorrhage, or        significant as it coming
    –   ARDS                            below the respiratory tract
• Requires good quality X-rays
3.
Supportive tests
(C1) CRP
• Inflammatory mediator

• Released from the liver after stimulation by the
  cytokine IL-6

• Produced as a part of SIRS/Sepsis.

• Reliable marker for infection and sepsis.

• CRP may have prognostic value in HAP.
   – ↑ CRP after 4 days of treatment noticed in non-
     survivors (marker of poor outcome)
(C2) Procalcitonin
• PCT increase in
  – invasive bacterial infections,
  – viral infections or
  – autoimmune diseases.


• Predict progression to severe sepsis and shock.

• been described as a prognostic marker in VAP

• ↑ levels in first week – worse outcome
(C3) Soluble Triggering Receptor
Expressed on Myeloid Cells (sTREM-1):
• sTREM-1 is a mediator the acute inflammatory
  response
• ↑ sTREM-1 in sepsis and shock - useful to
  monitor
• ↑ sTREM-1 in BAL fluid noticed in VAP
  – Cut off of >5 pg/mL ( Sensitivity 98% and
    Specificity 90%)
• s-TREM-1 in alveolar samples is marker of
  HAP,
• Draw back – requires BAL.
Flow chart to diagnose
         VAP
Treatment – Ask the
      expert
• END

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Pneumonia in hospitalized patients - Diagnostic Strategy

  • 1. Pneumonia in hospitalized patients Diagnostic Strategy Dr. Mahen Kothalawala MBBS, Dip in Micro, MD, MPH(NZ), Consultant Clinical Microbiologist Teaching Hospital Kandy Offsite consultant for TH Kegalle, DGH Matale, BH Nawalapitiya and Sirimawo Bandaranayake Specialized Hospital for Children
  • 3. Pneumonia in Hospitalized patients CAP HCAP HAP VAP In the first 48 In CAP with Pneumonia Pneumonia hrs of hospital recent contact developing developing admission with health after 48 to 72 after 48 of care system hrs after intubation admission 1. Early onset 2. Late onset
  • 5. Ventilator-associated pneumonia (VAP) burden • Common in Critical Care Unit • Estimated 8 to 20% of ICU patients • Occur up to 27% of mechanically ventilated patients • Pts intubated > 24hrs are 6 to 21 times more likely to develop VAP than those intubated <24hrs
  • 6. Mortality • Mortality rates – range from 20 to 50% • Some studies >70% (when caused by Multi resistant organisms) – Attributable mortality → difficult to quantify – due to confounders – But, VAP ↑mortality of the underlying disease by about 30%
  • 7. Morbidity of VAP • Prolongs ICU stay, • Prolongs mechanical ventilation, and • ↑↑ costs of hospitalization
  • 8. 3. Hospital-Acquired and ICU Pneumonia - Diagnosis
  • 9. HAP/VAP • “There is no doubt that the diagnosis and management of VAP remains one of the most controversial and challenging topics in management of critically ill patients.” (Chan C, Chest 2005;127:425 ) • The diagnosis of hospital-acquired pneumonia is complex.
  • 10. Diagnostic Testing for HAP/VAP • Diagnostic tests are ordered for two purposes: • To define – whether a patient has pneumonia – etiologic pathogen when pneumonia is present.
  • 11. Diagnosis of HAP/VAP • A. Clinical Strategy – A radiographic infiltrate, plus the presence of at least one of the three clinical data – Clinical pulmonary infection score (CPIS) • B. Microbiological Strategy – Non-invasive Methods • Blood Cultures: • Sputum Samples and Tracheal Aspirates: – Invasive Sampling Methods • Protected Specimen Brush (PSB): • Bronchoalveolar Lavage (BAL): • C. Usage of other inflammatory markers to support Δof HAP/VAP – CRP – Procalcitonin – sTREM 1
  • 12. A. Clinical Strategy (A1) A radiographic evidence of infiltrate, plus the presence of at least one of the three clinical data • new onset of fever, • purulent sputum, • leukocytosis (A2) Clinical pulmonary infection score (CPIS)
  • 13. A single clinical finding VS multiple features • Presence of radiographic infiltrate with • one clinical feature – fever, – leucocytosis, or – change of secretions – increase in volume or purulent • have high sensitivity but low specificity (especially for VAP). • Combination may improve specificity
  • 14. Comparison clinical criteria with PM findings • Presence of chest infiltrates, plus two of three clinical criteria resulted – 69% sensitivity – 75% specificity • Using three clinical variables → sensitivity declined • One variable → decline in specificity.
  • 15. A2. Clinical pulmonary infection score (CPIS) • A Tool with 6 easily obtained variables – body temperature, – white blood cell count, – quantity and purulence of tracheal secretions, – chest radiograph, – oxygenation, and, – bacterial growth in lower respiratory tracheal secretions
  • 16. Table 1. Clinical Pulmonary Infection Score (CPIS) Total Day #0 = _________ Total Day #3 = _________ Score Score Day 0 Day 3 Temperature, ºC Temperature, ºC ³38.5º - 38.9º = 1 point 38.5º - 38.9º = 1 point ³39.0º - 36.0º = 2 points 39.0º - 36.0º = 2 points Blood leucocytes, mm-3 Blood leucocytes, mm-3 <4.000 or >11.000 = 1 point <4.000 or >11.000=1 point 50% band forms = add 1 point 50% band forms = add 1 point Tracheal secretions Tracheal secretions Presence of non-purulent tracheal Presence of non-purulent tracheal secretions = 1 point secretions = 1 point Presence of purulent tracheal secretions Presence of purulent tracheal = 2 points secretions = 2 points Oxygenation: PaO2/FIO2 Oxygenation: PaO2/FIO2 >240 or ARDS = 0 point >240 or ARDS = 0 point < 240 and no ARDS = 2 points < 240 and no ARDS = 2 points Pulmonary radiography Pulmonary radiography No infiltrate = 0 point No infiltrate = 0 point Diffuse or patchy infiltrate = 1 point Diffuse or patchy infiltrate = 1 point Localized infiltrate= 2 points Localized infiltrate= 2 points Microbiological Data Microbiological Data Pathogenic bacterial cultured in rare or Pathogenic bacterial cultured in rare hight quantity or no growth = 0 or hight quantity or no growth = point 0 point Pathogenic bacterial cultured in Pathogenic bacterial cultured in moderate or heavy quantity = 1 moderate or heavy quantity = 1 point point Same pathogenic bacterial seen Same pathogenic bacterial seen on Gram stain = add 1 on Gram stain = add 1 point point
  • 17. Clinical pulmonary infection score (CPIS) • Score ranges from 0 to 12 • > 6/12 would correlate well → microbiologically confirmed HAP. • CPIS → used to select patients to treat safely with short-course antibiotic. • Some have shown that the score may lack sensitivity and specificity to establish → ΔHAP
  • 18. Pitfalls of CPIS • Observers variability • Microbiological results are often delayed (48hrs) / Not available always • Practical Approach – Usage with modifications • Modifications of CPIS – Use of Gram Stain where results available in one day – Eliminate the culture report and take same cut off
  • 19. Clinical Features without CXR findings – fever, – leukocytosis, – purulent sputum, and – a positive culture of a sputum or tracheal aspirate → nosocomial tracheobronchitis
  • 20. Nosocomial tracheo-bronchitis Vs HAP/VAP • Former no mortality • Can progress rarely to HAP/VAP • Contribute for cost of antibiotics
  • 21. B. Microbiological Strategy • Aim – to identify the specific pathogen by culture – (B1) Non respiratory culture • Blood • Pleural fluid – (B2) Lower respiratory culture (From LRT) • Invasive Method – BAL – PSB • Non Invasive method – Tracheal secretions
  • 22. Lower respiratory tract specimens • Useful to confirm the diagnosis and • Adjust antibiotic treatment if necessary
  • 23. Non invasive Method Tracheal Aspirates: • Gram stain and culture of TA- may provide relevant microbiological information, • Interpret with caution - as they not distinguish colonization from distal infection/pneumonia. • In intubated patients, as TA is obtained from deep of lung has higher diagnostic value
  • 24. (B2)Invasive Samples • lower airways can be easily accessed by fibreoptic flexible bronchoscopy. • samples → obtained under direct vision • Possible contamination is less
  • 25. Protected Specimen Brush (PSB): • Threshold to discriminate colonization and infection is 103 cfu/mL • PSB → high sensitivity (>70%) and specificity (80-90%) for infection. • Prior antibiotic Rx ↓detection sensitivity
  • 26. Bronchoalveolar Lavage (BAL): • Has appropriate Sensitivity and specificity to Δ HAP • Cutoff >104 cfu/mL • *> 2% of bacteria embedded in PMN or mφ cells in centrifuged BAL fluid → have a high specificity for infection (approaching 100%) • Antibiotic treatment readily ↓ intracellular bacterial count.
  • 27. Clinical Vs Microbiological Strategies The Clinical Approach Microbiological Approach • Overly (too) sensitive • Requires Invasive • Patients treated with procedures to achieve antibiotics when a non- infectious process is acceptable sensitivity and responsible for the clinical specificity findings. Such as – congestive heart failure, • Non invasive- Isolation false – atelectasis, positive pathogens – pulmonary thrombo embolism, – pulmonary drug reactions, • Negative results- highly – pulmonary hemorrhage, or significant as it coming – ARDS below the respiratory tract • Requires good quality X-rays
  • 29. (C1) CRP • Inflammatory mediator • Released from the liver after stimulation by the cytokine IL-6 • Produced as a part of SIRS/Sepsis. • Reliable marker for infection and sepsis. • CRP may have prognostic value in HAP. – ↑ CRP after 4 days of treatment noticed in non- survivors (marker of poor outcome)
  • 30. (C2) Procalcitonin • PCT increase in – invasive bacterial infections, – viral infections or – autoimmune diseases. • Predict progression to severe sepsis and shock. • been described as a prognostic marker in VAP • ↑ levels in first week – worse outcome
  • 31. (C3) Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM-1): • sTREM-1 is a mediator the acute inflammatory response • ↑ sTREM-1 in sepsis and shock - useful to monitor • ↑ sTREM-1 in BAL fluid noticed in VAP – Cut off of >5 pg/mL ( Sensitivity 98% and Specificity 90%) • s-TREM-1 in alveolar samples is marker of HAP, • Draw back – requires BAL.
  • 32. Flow chart to diagnose VAP
  • 33.
  • 34. Treatment – Ask the expert