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Sepsis due to Pneumonia

Ceva W Pitoyo
Pulmonology Division -Internal Medicine Dept.
High Care Unit
Faculty of Medicine Univ Indonesia
Cipto Mangunkusumo Central General Hospital
! Community acquired :
- Outpatient
- Inpatient
- Intensive care unit admitted
! Hospital acquired :
- Health care associated
- Hospital acquired (in ward)
- Ventilatory associated
Criteria of severity
! Guidelines vary about the features
used to identify a patient with severe
CAP at the time of admission to
Severe Pneumonia Criteria : BTS

! CURB65 Score : ≥ 2
- Confussion : score 1
- Uremia (BUN) > 19 mg/dl : score 1
- Respiratoty rate ≥ 30 : score 1
- Blood pressure : S < 90 or
D ≤ 60 : score 1
- ≥ 65 years : score 1
Pneumonia Severity Index (PSI) :
! Class I : Score : 0
! Class II : Score : ≤ 70
! Class III : Score : 71 – 90
! Class IV : Score : 91 – 130
! Class V : Score : > 130
Severe Pneumonia : ATS-IDSA
Major Criteria :
! Mechanical Ventilation
! Septic shock ( with vasopresor )

Minor Criteria :
! RR ≥30 x/mnt
! PaO2/FiO2 ≤ 250
! Multilobar infiltrate
! Decrease of consiousness / disorientation
! Uremia ( BUN ≥ 20 mg/dL)
! Leucopenia ( < 4000 /dL)
! Thrombocytopenia ( < 100.000 /dL)
! Hypothermia ( < 36 C)
! Hypotention (need of agresive fluid rescucitation)
Consensus on the management of Community-Acquired Pneumonia Infectious
Disease Society of America (IDSA) and American Thoracic Society (ATS) 2007
! Australian model called SMART-COP
attempted to predict receipt of
mechanical ventilation (whether
invasive or noninvasive) or
vasopressors, without regard for
location of care, and has been
externally validated in patients under
the age of 50 years
! Spanish model called CURXO-80.
Problems in definition of severity
! Ideally a definition of severity should show
physicians what they have to do to save
! The definition of severity in pneumonia
that deny the need of specific treatment
may fail to identify patients likely to
benefit from other therapy and vice versa
! Eg. A definition that rule out the need for
ICU may fail to identify patients likely to
benefit from specific antibiotic coverage.
! PSI and CURB-65 do not perform well at
predicting which patients will require ICU
admission or intensive therapy. They tend
to overestimate severity in patients with
advanced age or chronic organ failure and
underestimate severity in younger patients

! Angus DC, Marrie TJ, Obrosky DS, et al. Severe community-acquired pneumonia: use of intensive
care services and evaluation of American and British Thoracic Society Diagnostic criteria. Am J
Respir Crit Care Med 2002; 166:717–723
! Ewig S, de Roux A, Bauer T, et al. Validation of predictive rules and indices of severity for
community acquired pneumonia. Thorax 2004; 59:421–427
! Riley PD, Aronsky D, Dean NC. Validation of the 2001 American Thoracic Society criteria for severe
community-acquired pneumonia. Crit Care Med 2004; 32:2398–2402
! Kamath A, Pasteur MC, Slade MG, Harrison BD. Recognising severe pneumonia with simple clinical
and biochemical measurements. Clin Med 2003; 3:54–56
The ATS guidelines outperformed SMART-
COP, CURXO-80, and CURB-65 (P<0.05)
based on a health services reference definition of SCAP on

the basis of ICU admission and receipt of intensive therapy.

! Brown SM, Jones BE, Jephson AR, Dean NC. Validation of the Infectious
Disease Society of America/American Thoracic Society 2007 guidelines for
severe community-acquired pneumonia. Crit Care Med 2009; 37:3010–
! A prospective follow-on study by the
authors of the PSI suggested slightly
better prediction of 30-day mortality
than CURB or CURB-65
! PSI is more weighted toward age and
comorbidity and the CURB-65 is
more weighted toward acute
physiological dysfunction
Indication of ICU admission in

! CURB65 score : 4


! PSI class V


! IDSA – ATS : 1 Major or 2 Minor

Other Biomarkers for Severity
! Serum creatinine
! Bilirubin
! Lactate
! The ratio of arterial to inspired
oxygen (PO2 / FiO2)
! Hemoglobin concentrations
! Platelet count
SOFA Score
! Sepsis-related organ failure
assessment (SOFA) score
summarizes the dysfunction of
multiple organ systems in critical
illness and may prove useful as a
biomarker summary in severe
pneumonia, although this has not
been established
Novel Biomarkers
! Procalcitonin (the CALC-1 gene product) and
prohormone of calcitonin:
- Probably involved in chemoattraction and nitric
oxide production.
- Studies suggest possible utility in deciding on the
duration of antibiotic therapy
- Identifying a bacterial cause of lower respiratory
tract infection(or severe sepsis generally).
- Does not yet have established role in triage
decisions or severity assessments.

! The titer of bacterial DNA in the bloodstream may also

prove useful in predicting severe pneumonia, but
validation has not yet been completed
Treatment of Septic Pneumonia
Appropriate antibiotics reduce HAP mortality

Fiel S Chest 2001;119:412S-418S

©2001 by American College of Chest Physicians

! Substantial delay in treatment with
appropriate antibiotics is associated
with poor outcome in sepsis
generally and Pneumonia specifically

! Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment
of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118:146–155
! All three CAP management guidelines published
recently from North America1-3 recommend
combination antibiotic therapy initially for
patients with severe pneumonia, typically an
intravenous B-lactamase-stable B-lactam with
an intravenous macrolide or intravenous
“antipneumococcal” fluoroquinolone.

! 1 Mandell LA, Marrie TJ, Grossman RF, et al. Canadian guidelines for the initial management of
community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases
Society and the Canadian Thoracic Society. Clin Infect Dis 2000; 31: 383–421.
! 2 Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ. Practice guidelines for the
management of communityacquired pneumonia in adults. Clin Infect Dis 2000; 31: 347–82.
! 3 ATS Board of Directors. Guidelines for the management of adults with community-acquired
pneumonia. Am J Respir Crit Care Med 2001; 163: 1730–54.
! Severe bacteriemic pneumococcal
pneumonia have a significantly
greater risk of death (odds ratio 6·4,
95% CI 1·9–21·7) if they receive a
single antibiotic rather than
combination antibiotics on the first
day of admission

! Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe
bacteraemic pneumococcal pneumonia. Arch Intern Med 2001; 161: 1837–42
An#bio#c  Sensi#vity      
Non  ICU  Pneumonia  Cipto  Mangunkusumo  Hopital  
No Microbacteria Gram Antibiotic

1 Klebsiella Pneumoniae (-) Imipenem, Meropenem (94%)

2 Acinetobacter sp (-) Imipenem (79%)

3 Pseudomonas sp (-) Meropenem (73%)

4 Enterobacter aerogenes (-) Meropenem (86%)

5 E coli (-) Imipenem, Meropenem (92%)

6 Staphylococcus epidermidis (+) Linezolid (100%)

7 Acinetobacter calcoacitecus (-) Imipenem (69%)

8 Staphylococcus aureus (+) Vancomicyn, Linezolid (100%)

9 Streptococcus viridans (+) Gatifloxacin, Piperacillin-

Tazobactam, Levofloxacin,
Cefepime ((100%)
Antibiotic Sensitivity :
Wide Spectrum Non Carbapenem
Empirical Therapy for Pneumonia
(Cipto Mangunkusumo Data 2013)
IDSA: Treatment of Hospitalized
Severe Pneumonia / ICU
! First antibiotics should be given in ER (empirical
! No risk of Pseudomonas
–  IV B-lactam plus either
! IV Macrolide, or IV Fluoroquinolon
! Risk of Pseudomonas
–  Double agents : Antipseudomonal B-lactam
(cefepime, imipenem, meropenem, piperacillin/
tazobactam), plus
! Antipseudomonal Quinolone IV
–  Triple agents: Antipseudomonal B-lactam plus
IV aminoglicoside plus either
IV macrolide, or antipseudomonal IV quinolone
! Whenever culture shows
methicillin-resistant S. aureus
(MRSA), vancomycin or linezolid
should be added to the treatment
Management of Poor
! Consider of non-infection disease
! Consider of other less frequent
! Consider serologic tests
! Broaden the spectrum of antibiotic
! Consider bronchoscopy
Suppotive Treatments :
The Influence of Fluid is
! There’s considerable thoughts that severe
Pneumonia with systemic derangement such as
SIRS/Sepsis or ARDS, will lead to fluid
extravasations to interstitial of lung
parenchyma and increase the risk of hypoxemia
à some propose to restrict fluid in severe
à Singhi S et al : Extra cellular fluid and plasma
volume are increased in acute pneumonia and
the increase is linier to SpO2.
à Martin GS et al : Lung extra vascular fluid
correlate to the increase of mortality.
Other Supportive Treatments
! Inhalation of Hypertonic Saline to
reduce pathogen burden in the
! Immune Stimulation by cytokine
(systemic and inhalation) and / or
synthetic pathogen-associated
molecular pattern analogues
! Inhalation of Antimicrobial agents
à Non of them supported by
consistent trials.
Lessons learned from
Ventilator-Associated Pneumonia
Pneumonia after 48 hours of
-early onset = < 4 days
-late onset = > 4 days
Intubation increase risk of pneumonia
6 to 21 times
90% of all infections in intubated
1.  American  Thoracic  Society,  Infec#ous  Diseases  Society  of  America.    
Guidelines  for  the  management  of  adults  with  hospital-­‐acquired,  ven#lator-­‐associated,    
and  healthcare-­‐associated  pneumonia.      
2.  CDC. Guidelines for preventing health-care-associated pneumonia, 2003.
3.  Park  DR.  The  microbiology  of  ven#lator-­‐associated  pneumonia.
The Bugs
! Figure 1 from Park

Park  DR.  The  microbiology  of  ven#lator-­‐associated  pneumonia.  2005  

The Most Common Etiology of VAP
in Cipto Mangunkusumo 2013
The Bugs

Park  DR.  The  microbiology  of  ven#lator-­‐associated  pneumonia.  

Compara#on  of  Microbacterial  PaOern  Between  Early  and  Late  Onset  VAP  
in  ICU  /  HCU  of  Cipto  Mangunkusumo  2006  -­‐  2007  
No Kuman Dini Lambat

1 Acinetobacter anitratus 46,67% 45%

2 Pseudomonas aeruginosa 31,91% 30%

3 Klebsiella pneumonia 14,89% 20 %

4 Staph aureus 4,25 % 5%

5 Staph epidermidis 2,13 % 0%

6 Klebsiella ozaenae 2,13 % 0%

CM  Rumende.  Procalcitonin  dan  LBP  sebagai  prediktor  dan  petanda  prognos#k  VAP  di  ICU/HCU  RSCM  2006-­‐2007  
The Most Common Etiology of HAP (Non VAP)
In Cipto Mangunkusumo 2013
The Most Common Etiology of VAP
in Cipto Mangunkusumo 2013
Risks for MDR

American  Thoracic  Society,  Infec#ous  Diseases  Society  of  America.  Guidelines  for    
the  management  of  adults  with  hospital-­‐acquired,  ven#lator-­‐associated,  and    
healthcare-­‐associated  pneumonia.      
The  Most  Sensi#ve  An#bio#cs  for  
VAP  in  ICU  Cipto  Mangunkusumo  
No Kuman Gram Antibiotik

1 Klebsiella Pneumoniae (-) Imipenem (81%)

2 Pseudomonas sp (-) Amikacin (64%)

3 Acinetobacter sp (-) Imipenem, Meropenem (16%)

4 Acinetobacter calcoacitecus (-) Imipenem (40%)

5 Enterobacter (-) Meropenem (62%)

6 E Coli (-) Imipenem, Meropenem (100%)

7 Staph epidermidis (+) Vancomicyn, Linezolid, Teicloplanin

8 Staph aureus (+) Vancomicyn, Linezolid (100%)

9 Strep non hemolytic (+) -

10 Acinetobacter baumanii (-) -

Antibiotics on Late onset and Early onset VAP
with the risk of MDR

American  Thoracic  Society,  Infec#ous  Diseases  Society  of  America.  Guidelines  for    
the  management  of  adults  with  hospital-­‐acquired,  ven#lator-­‐associated,  and    
healthcare-­‐associated  pneumonia.      
Prophylaxys ‘Bundle’
! Head up 30 degree
! Oral care 4x/D
! Sterile Suction
! ‘Stress ulcer’ Prophylaxis
! ‘Hit hard and early weaning’

Thank You