and critical care medicine...division of pulmonary and critical care medicine discuss advances in...
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Brice TaylorAssistant ProfessorAssistant ProfessorDivision of Pulmonary and Critical Care Medicine
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Discuss advances in predicting prognosis
d d h k d d k Understand what we know (and don’t know) about the Microbiology
Recognize important treatment principles
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Epidemiology Predicting prognosis
h b l Pathogenesis/Microbiology Treatment
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40
30
35
20
25
10
15
0
5
ICU Nursing Home Bacteremic Elderly Hospitalized
Fine et al., JAMA 1996; 275:134
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M h t l Cli I f t Di Musher et al; Clin Infect Dis 2007 170 pts with pneumonia 19 4% had major cardiac event (7% had MI) 19.4% had major cardiac event (7% had MI) Higher mortality p<0.008
Ramirez et al; Clin Infect Dis 2008; 500 CAP patients 5.8% had MI
Perry et al; Am J Med 2011 50,119 veterans with pneumonia
% MI % CHF % h th i 1.5% MI, 10.2% CHF, 9.2% arrhythmia
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K t l A J R Kruger et al; Am J RespCrit Care Med 2010 728 CAP patients 728 CAP patients outcomes: 28‐day and 180‐day mortality y y MR‐proADM, CRP, Procalcitonin, etc
C di bi k Cardiac biomarkers more predictive than inflammatory markersinflammatory markers
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Need one MAJOR Need one MAJOR or three MINOR
Mandell Clin Infect Mandell Clin Infect Dis 2007
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Kruger; Eur Resp J 2008 1671 CAP patients PCT increased with CRB‐65 score PCT higher in pts who died, similar accuracy to CRB‐65 PCT < 0.228 identified low‐risk pts (99% NPV)
Huang; Ann Emerg Med 2008 1651 CAP patients Only 2 pts with PCT <0.1 died
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Epidemiology Predicting prognosis
h b l Pathogenesis/Microbiology Treatment
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f Sources of bacteria Aspiration from colonized oropharynx Aspiration from sinuses Aspiration from stomach Hematogenous spread (i.e. septic emboli) Aerosol (TB, legionella, viruses)g
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In nonsevere CAP, immune response is localized Local production of IL‐1, IL‐6, TNF‐alpha IL‐8 in involved lung only
In severe CAP Higher TNF and IL‐6 in contralateral lung, serum Suggests role of excessive inflammatory response
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O ti t I ti t Oupatient S. pneumoniae M pneumoniae
Inpatient S pneumoniae M pneumoniaeM. pneumoniae
H. influenza C. Pneumoniae
M. pneumoniae C pneumoniae H. influenza
viruses Legionella Aspiration
ICU ICU S. aureus Gram negative enterics ?MRSA
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18% of 338 CAP 100 18% of 338 CAP patients had positive paired viral serology
6708090
p gy(4x rise in titers) Influenza (27 A, 10 B),
fl 30405060
*
Parainfluenza (11), RSV (5), Adenovirus (5)
Half pure viral, half 0102030
Half pure viral, half mixed infection viral
mixed
s. pneumoDe Roux et al Chest 2004* p < 0.05
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d k Incidence unknown, often after viral infectioninfection
Distinct from nosocomial MRSA Severe, necrotizing Panton Valentine Leukocidin
USA 300 strain
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h % i 95 Nursing home patients admitted for aspiration pna
60
% organism
aspiration pna Cultures by bronchwithin 4 hours
40
50
4 Anerobes in only 11 6 of these responded to 20
30
“inappropriate” therapy
0
10
0Anaerobes Gram Negs S. aureus
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Health Care Community
Acquired Hospital Acquired
Health Care Associated Pneumonia(HCAP)
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MRSA Pseudomonas
l ESBL E Coli KPC Klebsiella
b h Acinetobacter, stenotrophomas others
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HCAP criteria (any one) Hospitalization for >48 hrs in past 90 days Residence in nursing home or extended care Home infusion therapy or wound care Chronic dialysis Family member with MDR pathogen
Treat like HAP/VAP ith broad spectr m Ab Treat like HAP/VAP with broad spectrum Abx
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2001: Morin & HadlerHealthcare associated infection (MRSA bacteremia) • Hospitalization in past 12 months2001: Morin & Hadler p p• Dialysis within 12 months • Indwelling catheter at home prior to admission
Healthcare associated bloodstream infection (MRSA)IV i f i d t h i t d
2002: Friedman et al • IV infusion or wound care at home in past 30 days• Hemodialysis or infusion clinic visit in past 30 days• Hospitalized for >2 days in past 90 days• Nursing home or long‐term care facility
2004: Tacconelli et al
Healthcare associated bacteremia (MRSA)• IV therapy or nursing/wound care at home•Ambulatory care visit in past 30 days• Chronic Hemodialysis• Hospitalized >2 days in past 6 months
2005: ATS/IDSA
• Hospitalized >2 days in past 6 months• Nursing home or long‐term care facility
Healthcare associated pneumonia• Hospitalization >2 days in past 90 days
guidelinesp y p 9 y
• Nursing home or extended term care facility • Home infusion therapy or wound care• Chronic dialysis within 30 days
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Single center retrospective analysis, n=639 Primary endpoint – infection with drug‐resistant organism
The HCAP definition had a specificity of only 48.6% for drug resistant pathogens
Misclassified one‐third of patients
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Recent hospitalization Nursing Home Residence
h h d l Chronic hemodialysis Home health/wound care
l b h Family member with MDR organism
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l h d Multicenter Prospective cohort study (n=104)
Patients > 75 yo with severe pneumonia requiring Patients > 75 yo with severe pneumonia requiring mechanical ventilation
Looked at microbial etiology in CAP vs NHAP
Assigned ADL score as marker of functional status
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Nursing home Home (n = 47) (n = 57) p‐value
Pathogen, %‐S. pneumoniae
(%)9
(%)14 0.380S. pneumoniae
‐‐S. aureus‐ ‐MRSA‐ Pseudomonas
929 64
14702
0.3800.002*0.0530.448
In‐hospital mortality (%) 57.4 52.6 0.8
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ACTIVITIES OF DAILY LIVING
Transfer
SCORING
1 = Independent Feeding Bathing
p2 = Partially dependent 3 = Completely dependentg
Dressing Toileting 6 fully independentg Continence
6 = fully independent18 = fully dependent
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60
50
60
30
40
S. aureusGNR and PSA
20
3GNR and PSAS. pneumoniae
0
10
ADL I ADL II ADL III
El Solh et al. 2001 Am J Resipir Crit Care Med
ADL I ADL II ADL III
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Recent hospitalization Nursing Home Residence
h h d l Chronic hemodialysis Home health/wound care
l b h Family member with MDR organism
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h d Retrospective cohort study 3074 pts on HD who were hospitalized for pneumoniaO i id tifi d i l 8 % Organism identified in only 18.2%
Gram negatives (11 1%) Gram positives (4 8%)Gram negatives (11.1%) Gram positives (4.8%)
Pseudomonas 2.8 %Klebsiella 1 6 %
S pneumoniae 3.4 %Other streptoccocci 1 0 %Klebsiella 1.6 %
H influenzae 1.5 %Other streptoccocci 1.0 %Staphylococcus sp 0.4 %
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Guo et al Nephrol Dial Transplant 2008
h d
Guo et al. Nephrol Dial Transplant 2008
Retrospective cohort study (n = 60,610) Organism identified in only 15.6%
Gram negatives (4.0%) Gram positives (4.73%)
Pseudomonas 1.2 %Klebsiella 1.1 %
S pneumoniae 2.56 %Other streptoccocci 0.43 %
H influenzae 0.47 %E coli 0.23 %
Staphylococcus sp 1.73 %
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f Retrospective cohort study (n=128) of hemodialysis patients admitted with pneumonia
NO other HCAP risk factorsd d h Compared outcomes in patients treated with
CAP vs HCAP guidelines Mortality Length of stay Time to oral therapy
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CAP HCAP P valueCAP HCAP P value
Age (mean, SD) 54.7 (15.7) 56.7 (15.6) 0.486
PSI (mean SD) 93 1 (29 5) 101 7 (31 4) 0 127PSI (mean, SD) 93.1 (29.5) 101.7 (31.4) 0.127
CCI 4.5 (1.8) 4.1 (1.5) 0.221
O tOutcomes
Length of stay (days)
5.1 (3.7) 9.4 (5.5) <.0001*
Time to oral tx(days)
3.2 (2.0) 9.2 (6.8) <.0001*
Hospital mortality 0 2 0.465p y
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Epidemiology Predicting prognosis
h b l Pathogenesis/Microbiology Treatment
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NO PSEUDOMONAL RISK NO PSEUDOMONAL RISK FACTORS
Beta‐lactam (ceftriaxone)
PSEUDOMONAL RISK FACTORS
Beta‐lactam (cefepime, PLUSMacrolide
pip‐tazo), doripenem, aztreonam if PCN allergyPLUS
OR
Respiratory quinolone
PLUSCipro (or levo)
OR Beta lactam PLUS Respiratory quinolone Beta lactam PLUS
Aminoglycoside PLUSmacrolideOR respquinolone
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40 515 pna patients Randomized to levaquin alone vs 30
35
levaquin alone vsBL + M
Equivalent for non‐ 20
25
BL+Mqsevere CAP
Lower 30‐day 10
15levo
mortality in severe CAP
0
5
10
0PSI < V PSI V
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First dose antibiotics within 6 hours Oxygenation assessment within 24 hrs
b d d Correct antibiotic/s administered Blood cultures w/i 24 hrs
k d Smoking cessation advice Pneumococcal and influenza vaccine
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Most pts have clinical response in 3 days Switch to oral antibiotics when: Improvement in cough and dyspnea Decreasing wbc count Functional GI tract Afebrile at least 8 hrs (Ok to switch if still febrile as long as other features are present)
Discharge home same day, outcomes same as if hospitalized for entire course
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ff <7‐day course similar efficacy to prolonged course in severe CAPd l d 8 days equivalent to 14 days in HAP/VAP
(except pseudomonas)
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f Guidelines recommend coverage for MRSA, pseudomonas, and resistant Gram negatives
b d f h CAP tx may be adequate for patients with Good functional status No recent antibiotics Hemodialysis as only risk factor ??
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“(A tibi ti ) i t “(Antibiotic) resistance is 1 of the 3 greatest threats to human health, as well as national security and public safety of some public safety of some regions”
“Antimicrobial overuse is the key driver of resistance”resistance
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Until guidelines are revised, consider subsets of HCAP pts that can be treated with CAP tx
d l f b h Limited role for combination therapy De‐escalation when clinical improvement
d l d d Avoid prolonged duration
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f Mortality from CAP is high and likely related to underlying cardiovascular disease
l f d Early recognition of severe CAP reduces mortality (PSI, CRB‐65, PCT)
h h h d l PCT has high neg pred value in CAP HCAP is clearly a heterogenous disease– not
ll d hall patients need MDR therapy Prompt deescalation and limited duration of
b f dantibiotics is safe and appropriate