Transcript Community acquired pneumonia: Update and review for the

Community acquired
pneumonia
Bharat Awsare MD FCCP
Division of Pulmonary and Critical Care Medicine
Assistant Professor of Medicine
Director, Medical Intensive Care Unit
Thomas Jefferson University Hospital
Pneumonias – Classification
CAP
• Community Acquired
HCAP
• Health Care Associated
HAP
• Hospital Acquired
ICUAP
• ICU Acquired
VAP
• Ventilator Acquired
Nosocomial Pneumonias
CAP – Two Types of Presentations
Classical
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Sudden onset of CAP
High fever, shaking chills
Pleuritic chest pain, SOB
Productive cough
Rusty sputum, blood tinge
Poor general condition
High mortality up to 20%
in patients with
bacteremia
S.pneumoniae causative
Atypical
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Gradual & insidious onset
Low grade fever
Dry cough, No blood tinge
Walking CAP
Low mortality 1-2%; except
in cases of Legionellosis
Mycoplasma, Chlamydiae,
Legionella, Ricketessiae,
Viruses are causative
Scope of the problem
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5 million cases/year
10 million office visits
1 million admissions/year
100,000 ICU admissions
Estimated cost: $12 billion*
◦ Inpatient (20%)
◦ Outpatient (80%)
$10 billion
$2 billion
*Colice GL et al. Am J Resp Crit Care Med (2006)176:913-920.
Incidence of CAP per age (in 1000’s)
1400
1171 1207
1200
1000
1071
898
800
684
600
# of cases
400
200
83
0
<5
5 to 18-24 25-44 45-64 >65
17
CAP mortality per age (in 1000’s)
80
74.9
70
60
50
40
# of deaths
30
20
10
2
5.7
0
<4
5 to 14 15-24
25-44
45-64
>65
Mortality in CAP
Most common cause of severe sepsis
 6th leading cause of death
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◦ Leading cause of death from infection
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Mortality has not changed in 4 decades
◦ Outpatient
◦ Inpatient
◦ ICU
1%
5-10%
20-40%
Age adjusted death rates
www.cdc.gov/mmwr
Risk factors
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Major
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COPD/smoking
Alcoholism
Chronic heart disease
Diabetes
1/3 patients
previously healthy
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Other risk factors
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Poor dentition
Renal failure
Hepatic disease
CVA
Immunodeficiency
Malnutrition
Microbiology
Outpatient
Inpatient (non-ICU)
Inpatient (ICU)
S pneumoniae
S pneumoniae
S pneumoniae
M pneumoniae
M pneumoniae
Legionella spp
H influenzae
C pneumoniae
H influenzae
C pneumoniae
H influenzae
Gram negative bacilli
M catarrhalis
Legionella spp
S aureus
Viruses*
Viruses*
*• Influenza A and B
• Adenovirus
• Respiratory syncitial virus
• Parainfluenza
40-70% of patients with CAP have no
organism identified (fastidious growth of S.
pneumoniae, H. influenzae)
Modern methods to determine
etiology of CAP
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Adults admitted with CAP over 1 year
Microbiologic testing
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Sputum culture
Blood culture
Nasopharyngeal sampling
Sputum samples analyzed by PCR
Nasal samples analyzed by PCR
Serologic testing for M pneumoniae and
Chlamydophila pneumoniae, and viruses
◦ Urine antigen assay for S pneumoniae, Legionella
Results
N = 184
 Organism identified in 124 (67%)
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◦ 35% of these had 2+ organisms
For complete sampling, organism
identified in 89%
 Sputum PCR increased yield over
traditional methods
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Bacterial and viral yields
Incidence of co-infections
Etiology in special situations
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Alcohol, poor dental hygiene: anaerobes
Sick hunting dogs: blastomycosis
Bats, bird droppings: histoplasmosis
Travel to SW US: coccidiomycosis
Birds: Chlamydia psittaci
Rabbits: Francisella tularensis
Farm animals, parturient cats: Coxiella burnetii (Q
fever)
Post-influenza: S. aureus, S. pneumoniae, S.
pyogenes, H. influenzae
H1N1 outbreak April 2009
61 million affected
 13,000 deaths
 90% hospitalizations, 87% deaths
occurred in patients less than 65
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Obesity
Pregnancy
Asthma
Young age
Community acquired MRSA
New strain of MRSA (USA 300 strain)
 Not traditional risk factors for MRSA
 Often follow influenza viral infection
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◦ Influenza with bilateral cavitary pneumonia
Skin/soft tissue infection
 Risk factors
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◦ Young age
◦ Close living conditions
◦ Skin contact, cuts/abrasions
Necrotizing pneumonia (CA-MRSA)
Eur Respir J 2009; 34: 1470–1476
CA-MRSA virulence factors
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Panton-Valentine leukocidin (PVL) gene
◦ Skin/soft tissue infections
◦ Severe cavitary pneumonia
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Type IV mecA gene
◦ Resistance to beta lactams/methicillin
CA-MRSA therapy
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Antibiotics
◦ Vancomycin (reports of poor outcomes with
monotherapy*)
◦ Linezolid
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Anti-toxin
◦ Clindamycin
◦ Linezolid
*Micek et al. Chest 2005(128):2732.
Assessment of severity
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Physicians overestimate risk of death
◦ Unnecessary admissions
◦ Increased cost
◦ Potential for morbidity related to
hospitalization
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Multiple tools available
◦ PORT/Pneumonia Severity Index
◦ CURB-65
◦ ATS/IDSA
PORT Pneumonia Severity Index
ED’s using PSI reduced rate of
hospitalization in low risk groups
NO DIFFERENCES IN MORTALITY
CURB-65 algorithm
CRB-65 algorithm
ATS/IDSA: site of care decisions
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Severity scores should be used to identify
patients for outpatient therapy
◦ CURB-65
◦ PSI
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Scores should always be supplemented by
physician determination of other factors
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Psychosocial factors
Support resources
Compliance
Ability to tolerate oral therapy
Failure of outpatient therapy
Laboratory testing (hospitalization)
Chest X-ray
 CBC with differential
 Electrolytes
 BUN/creatinine
 Glucose
 Liver enzymes
 Oxygen saturation
 Gram stain/cultures of sputum (??)
 Blood cultures (??)
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Chest x-ray
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Radiology + clinical scenario are gold
standard for diagnosis
Not mandatory (outpatient)
Information provided
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Extent of disease
Cavitation
Complications (effusion)
Alternate or co-existing diagnosis (neoplasm)
Information not provided
◦ Causative organism
CXR Pattern
Possible Pathogens
Lobar
S.pneumo, Kleb, H. influ, Gram Neg
Patchy
Atypicals,Viral, Legionella
Interstitial
Viral, PCP, Legionella, mycoplasma,
chlamydia
Cavitation
Anerobes, Kleb,TB, S.aureus, Fungi, caMRSA,
Nocardia
Large effusion
Staph, Anaerobes, Klebsiella
Miliary pattern
Mtb, Fungi
Widened
mediastinum with
effusions
Inhalational anthrax
Chest Xray in CAP
Cavitary pneumonia
Parapneumonic effusion
CXR – PA and Lateral Views
Round Pneumonic Consolidation
Special Forms of Pneumonia
Empyema
Microbiologic testing
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Utility for all CAP uncertain
◦ False negatives
◦ Not cost effective
◦ Diagnosis may not affect outcome
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IDSA/ATS recommendations
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Severe CAP (ICU)
Optional for outpatient
Diagnosis uncertain
Structural lung disease
Pleural effusion
Biomarkers for CAP
Procalcitonin (available)
 C-reactive protein (available)
 Pro-adrenomedullin
 Co-peptin
 Natriuretic peptides
 Cortisol
 Pro-atrial natriuretic peptide
 Coagulation markers
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Brar NK and Niederman MS, Ther Adv Respir Dis (2011) 61-78
Procalcitonin
Precursor of calcitonin
 No hormonal effects
 Increased with bacterial infection
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◦ Toxin mediated (lipopolysaccaride)
◦ Cytokine mediated (IL-6, IL-1, TNF)
◦ Cell mediated response mediated
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Decreased with viral infection
◦ Cytokine mediated (IFN-gamma)
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Also increased with trauma, burns
Procalcitonin: Pros/cons
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Pros
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Helps reduce antibiotic duration
Helps antibiotic exposure
Helps convert to oral therapy
May help with early discharge
Cons
◦ Inadequate accuracy to discriminate bacterial
vs. viral infection
◦ Accuracy too low to withhold therapy
Timing of antibiotics
Multiple studies show delayed antibiotics
associated with increased mortality
(Houck et al 2004, Meehan et al 1997)
 4 hour antibiotic was adopted as quality
core measure
 Implementation of 4 hours had problems:
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◦ Misdiagnosis of CAP*
◦ Inappropriate antibiotics*
◦ Antibiotic toxicity including C difficile
*Kanwar et al. Chest 2007:1865-1869.
Timing of antibiotics
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IDSA/ATS guidelines recommendation
◦ First dose of antibiotics in ED (6-8 hrs)
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Earlier antibiotics probably better with
severe sepsis
Factors influencing antibiotics
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Setting
◦ Outpatient
◦ Inpatient
◦ ICU
Comorbidities
 Risk factors for certain pathogens
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 Resistant pneumococcus
 Resistant gram negatives
 Pseudomonas
 Community acquired MRSA
Monotherapy vs. combination
therapy
Multiple recent studies show improved
outcomes with combination therapy1-5
 Odds ratio of death with monotherapy
ranged from 1.5-6x adjusted for severity
 Benefit most in those with severe CAP
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◦ Benefit only seen when macrolides used6
1Waterer
et al. Arch Int Med 2001(161):1837.
2Baddour et al. Am J Respir Crit Care Med 2004(170):440.
3Tessmer et al. J Antimicrob Chemother 2009(63):1025.
4Rodriguez et al. Crit Care Med 2007(35):1493.
5Restrepo et al.Eur Respir J 2009(33):153.
6Martin-Loeches et al. Intensive Care Med 2010(36):612.
Beneficial effects of macrolides
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Atypical pathogen co-infection seen in 1/3 of
pneumococcal CAP
◦ Quinolones, tetracyclines do not offer same benefit
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Anti-inflammatory properties
◦ Modification of heat shock protein-70 and p38 signaling
pathways
◦ Improve chemotactic and phagocytic function of
macrophages
◦ Mucociliary function enhancement
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Reduce virulence factors
◦ Toxin production
◦ Biofilm
◦ May reduce bacterial load with less cell wall lysis by betalactams = less pro-inflammatory response
Antimicrobial therapy
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Outpatient
◦ Previously healthy
◦ No antibiotics within last 3 months
Macrolide
 Doxycycline
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Antimicrobial therapy
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Outpatient
◦ Comorbidities
◦ Previous antibiotics within 3 months
◦ High resistance to S pneumoniae
Respiratory fluoroquinolone
 Beta-lactam plus macrolide
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Antimicrobial therapy
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Inpatient, non-ICU
Beta-lactam plus macrolide
 Respiratory fluoroquinolone
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Antimicrobial therapy
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Inpatient, ICU
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Beta lactam plus:
◦ Respiratory fluoroquinolone or
◦ Macrolide
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PCN allergic:
◦ Aztreonam plus fluoroquinolone
Antimicrobial therapy
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Pseudomonas is consideration
 Anti-pseudomonal/pneumococcal beta-lactam
(Pip-tazo, cefepime, imipenem, meropenem)
PLUS one of the following:
◦ Ciprofloxacin or Levofloxacin
◦ Azithromycin plus aminoglycoside
◦ Antipneumococcal fluroquinolone plus
aminoglycoside
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PCN allergy: substitute aztreonam for
beta-lactam
Antimicrobial therapy
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If CA-MRSA is consideration
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Add vancomycin or linezolid
◦ If vancomycin, consider clindamycin for antitoxin therapy
Factors for switch to oral therapy
Hemodynamic stability
 Clinical improvement
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◦ Cough, dyspnea better
◦ Afebrile > 8 hours
◦ WBC normalizing
Adequate oral intake
 No GI absorption issues
 Patients do not need to be observed
overnight after switch to oral tx
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Duration of antibiotics
Treated for minimum 5 days (ATS), 7 days (BTS)
 Longer if resistant organism, extra-pulmonary
disease
 Afebrile for 48-72 hours
 No more than 1 sign of clinical instability
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Number of signs of instability correlate
with mortality, readmission
Halm EA, et al.. Arch Intern Med 2002; 162:1278–84.
Does everyone need follow up
chest Xray?
Cohort study in 3398 patients
 1.1% risk of lung cancer at 90 days
 2.3% risk of lung cancer at 5 years
 Multivariate analysis
◦ Age > 50 most strongly associated
◦ Male sex
◦ Smoking
 Conclusion: follow-up CXR not necessary in patients
<50 years old
 Should be done at 7-12 weeks
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Tang et al. Arch Intern Med 2011;171:1193.
Long term consequences of CAP
Survivors of CAP had sustained increased
mortality for 2+ years1
 CAP survivors had 1 year mortality 2.5x
greater than age/sex matched controls2
 IL-6 and IL-10 elevation at discharge
associated with increased 90d mortality3
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1Brancati
et al. Lancet 1993(342):30.
2Kaplan et al. Arch Intern Med 2003(163):317.
3Yende et al. Am J Respir Crit Care Med 2008(177):1242.
Long term consequences of CAP
Medicare database
 158,960 CAP pts
 794,333 hospitalized
controls matched for
age, sex, race
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Kaplan et al. Arch Intern Med 2003(163):317.
CAP was associated with lower 10 year
survival compared to age matched control
Possible mechanisms to explain long
term mortality
Cardiovascular disease effects1
 Associations between CAP and acute
coronary events2
 Associations between CAP and
subsequent cardiovascular events3
 Destabilize atheromatous plaques
 Induce procoagulant state
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1Koivula
et al. Arch Intern Med 1999(159):1550.
2Ramirez et al. Clin Infect Dis 2008(47):182.
3Smeeth et al. NEJM 2004(351):2611.
QUESTIONS?