Transcript Paras Patel MD. Assistant Professor of Internal Medicine, Division of Infectious disease.

Paras Patel MD.
Assistant Professor of Internal Medicine,
Division of Infectious disease. ETSU
Alphabet Soup for Pneumonia
•
HAP: Hospital-acquired pneumonia
–
•
VAP: Ventilator-associated pneumonia
–
•
Long-term care facility (NH), hemodialysis, outpatient chemo, wound
care, etc.
CAP: Community-acquired pneumonia
–
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≥ 48 h from endotracheal intubation
HCAP: Healthcare-associated pneumonia
–
•
≥ 48 h from admission
Outside of hospital or extended-care facility
Community Acquired Pneumonia
• Definition:
– … an acute infection of the pulmonary
parenchyma that is associated with at least
some symptoms of acute infection,
accompanied by the presence of an acute
infiltrate on a chest radiograph, or
auscultatory findings consistent with
pneumonia, in a patient not hospitalized or
residing in a long term care facility for > 14
days before onset of symptoms.
3 Bartlett. Clin Infect Dis 2000;31:347-82.
Community Acquired Pneumonia
• Epidemiology:
– 4-5 million cases annually
– ~500,000 hospitalizations
– ~45,000 deaths
– Mortality 2-30%
• <1% for those not requiring hospitalization
Cdc.gov/data
2007.
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Community Acquired Pneumonia
• Epidemiology: (contd)
– fewest cases in 18-24 yr group
– probably highest incidence in <5 and >65 yrs
– mortality disproportionately high in >65 yrs
1400
1171 1207
1200
1000
1071
898
800
684
600
# of cases
400
200
83
0
5
<5
5 to 18-24 25-44 45-64 >65
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Community Acquired Pneumonia
Mortality
80
74.9
70
60
50
# in 40
1000s
# of deaths
30
20
10
2
5.7
0
6
<4
5 to 14 15-24
25-44
45-64
>65
Age-specific
Rates of Hospital
Admission by
Pathogen
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Marsten. Community-based pneumonia incidence study group.
Arch Intern Med 1997;157:1709-18
CAP – Pathogenesis
• Inhalation, aspiration
and hematogenous
spread are the 3 main
mechanisms by which
bacteria reaches the
lungs
Inhalation
Aspiration
Hematogenous
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Pathogenesis
• Primary inhalation: when organisms bypass normal
respiratory defense mechanisms or when the Pt
inhales aerobic GN organisms that colonize the upper
respiratory tract or respiratory support equipment
• Aspiration: occurs when the Pt aspirates colonized
upper respiratory tract secretions
– Stomach: reservoir of GNR that can ascend, colonizing the
respiratory tract.
• Hematogenous: originate from a distant source and
reach the lungs via the blood stream.
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Community Acquired Pneumonia
• Risk Factors for pneumonia
–
–
–
–
–
–
–
–
–
age
smoking
asthma
immunosuppression
institutionalization
COPD
PVD
Dementia
HIV/AIDS
ID Clinics 1998;12:723.
10Am J Med 1994;96:313
Community Acquired Pneumonia
• Risk Factors in Patients Requiring Hospitalization
– older, unemployed
– common cold in the previous year
– asthma, COPD; steroid or bronchodilator use
– Chronic disease
– amount of smoking
Farr BM. Respir Med 2000;94:954-63
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Community Acquired Pneumonia
• Risk Factors for Mortality
– age
– bacteremia (for S. pneumoniae)
– extent of radiographic changes
– degree of immunosuppression
– amount of alcohol
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Community Acquired Pneumonia
Microbiology
– S. pneumoniae: 20-60%
– H. influenzae: 3-10%
– Chlamydia pneumoniae: 4-6%
– Legionella spp. 2-8%
– S. aureus: 3-5%
– Gram negative bacilli: 3-5%
– Viruses: 2-13%
– Mycoplasma pneumonaie: 1-6%
40-60% - NO CAUSE IDENTIFIED
2-5% - TWO OR MORE CAUSES
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Bartlett. NEJM 1995;333:1618-24
Streptococcus pneumonia
(Pneumococcus)
 Most common cause of CAP
 About 2/3 of CAP are due to S.pneumoniae
 These are gram positive diplococci
 Typical symptoms (e.g. malaise, shaking chills
fever, rusty sputum, pleuritic chest pain, cough)
 Lobar infiltrate on CXR
 May be Immuno suppressed host
 25% will have bacteremia – serious effects
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Atypical Pneumonia
• #2 cause (especially in younger population)
• Commonly associated with milder Sx’s: subacute onset, nonproductive cough, no focal infiltrate on CXR
•
Mycoplasma: younger Pts, extra-pulm Sx’s (anemia, rashes),
headache, sore throat
• Chlamydia: year round, URI Sx, sore throat
• Legionella: higher mortality rate, water-borne outbreaks,
hyponatremia, diarrhea
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Viruses and Pneumonia
Pneumonia in the normal host
• Adults or Children
• Influenza A and B, RSV, Adenovirus, Para Influenza
Pneumonia in the immuno-compromised
• Measles, HSV, CMV, HHV-6, Influenza viruses
• Can cause a primary viral pneumonia. Cause partial
paralysis of “mucociliary escalator” - increased risk of
secondary bacterial LRTI. S.aureus pneumonia is a
known complication following influenza infection.
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Other bacteria
• Anaerobes
– Aspiration-prone Pt, putrid sputum, dental disease
• Gram negative
– Klebsiella - alcoholics
– Branhamella catarrhalis - sinus disease, otitis, COPD
– H. influenza
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S. aureus CAP – Dangerous
 This CAP is not common; Multi lobar Involvement
 Post Influenza complication, Class IV or V
 Compromised host, Co-morbidities, Elderly
 CA MRSA – A Problem; CA MSSA also occurs
 Empyema and Necrosis of lung with cavitations
 Multiple Pyemic abscesses, Septic Arthritis
 Hypoxemia, Hypoventilation, Hypotension common
 Vancomycin, Linezolid are the drugs for MRSA
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Diagnosis and Management
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Clinical Diagnosis
• Suggestive signs and symptoms
• CXR or other imaging technique
• Microbiologic testing
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Signs and Symptoms
• Fever or hypothermia
• Cough with or without sputum, hemoptysis
• Pleuritic chest pain
• Myalgia, malaise, fatigue
• GI symptoms
• Dyspnea
• Rales, rhonchi, wheezing
• Egophony, bronchial breath sounds
• Dullness to percussion
• Atypical Sx’s in older patients
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Clinical Diagnosis: CXR
• Demonstrable infiltrate by CXR or other imaging
technique
– Establish Dx and presence of complications (pleural
effusion, multilobar disease)
– May not be possible in some outpatient settings
– CXR: classically thought of as the gold standard
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Chest Radiograph
May show hyper-expansion, atelectasis or infiltrates
Normal
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Pneumonia
Infiltrate Patterns
Pattern
Possible Diagnosis
Lobar
S. pneumo, Kleb, H. flu, GN
Patchy
Atypicals, viral, Legionella
Interstitial
Viral, PCP, Legionella
Cavitary
Anaerobes, Kleb, TB, S. aureus,
fungi
Staph, anaerobes, Kleb
Large effusion
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Clinical Diagnosis: Recommended
testing
• Outpatient: CXR, sputum Cx and Gram stain not
required
• Inpatient: CXR, Pox or ABG, chemistry, CBC, two sets
of blood Cx’s
– If suspect drug-resistant pathogen or organism not covered
by usual empiric abx, obtain sputum Cx and Gram stain.
– Severe CAP: Legionella urinary antigen, consider
bronchoscopy to identify pathogen
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Community Acquired Pneumonia
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To Admit or Not?
Pneumonia Severity & Deciding Site of Care
•
Using objective criteria to risk stratify & assist in decision
re outpatient vs inpatient management
•
PSI
•
CURB-65
•
Caveats
– Other reasons to admit apart from risk of death
– Not validated for ward vs ICU
– Labs/vitals dynamic
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Pneumonia Severity Index
Class
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Points
Mortality*
Site of Care
I
<51
0.1%
OutPatient
II
51-70
0.6%
OutPatient
III
71-90
2.8%
In or OutPatient
IV
91-130
9.5%
Inpatient
V
>130
26.7%
Inpatient
CURB 65 Rule – Management of CAP
CURB 65
Confusion
BUN > 30
RR > 30
BP SBP <90
DBP <60
Age > 65
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CURB 0 or 1
Home Rx
CURB 2
Short Hosp
CURB 3
Medical Ward
CURB 4 or 5
ICU care
Who Should be Hospitalized?
Class I and II
Usually do not require hospitalization
Class III
May require brief hospitalization
Class IV and V
Usually do require hospitalization
Severity of CAP with poor prognosis
RR > 30; PaO2/FiO2 < 250, or PO2 < 60 on room air
Need for mechanical ventilation; Multi lobar involvement
Hypotension; Need for vasopressors
Oliguria; Altered mental status
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CAP – Criteria for ICU Admission
Major criteria
 Invasive mechanical ventilation required
 Septic shock with the need of vasopressors
Minor criteria (least 3)
 Confusion/disorientation
 Blood urea nitrogen ≥ 20 mg%
 Respiratory rate ≥ 30 / min; Core temperature < 36ºC
 Severe hypotension; PaO2/FiO2 ratio ≤ 250
 Multi-lobar infiltrates
 WBC < 4000 cells; Platelets <100,000
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Traditional Treatment Paradigm
Conservative start with ‘workhorse’ antibiotics
Reserve more potent drugs for non-responders
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New Treatment Paradigm
Hit hard early with appropriate antibiotic(s)
Short Rx. Duration; De-escalate where possible
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The Effect of the Traditional Approach
Inappropriate therapy (%)
50
40
45
34
30
20
17
10
0
CAP
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HAP
HAP on CAP
Kollef, et al. Chest 1999;115:462–474
New data – Don’t Wait for Results !
Mortality (%)
n=75
p<0.001
Switching after
susceptibility results
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Adequate treatment
within ‘a few hours’
Tumbarello, et al. Antimicrob Agents Chemother 2007;51:1987–1994
New data – The Speed of Delay ! (Class 4,5)
90
Survival (%)
80
70
60
50
40
Each hour of delay carries
7.6% reduction in survival
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20
10
0
0.5
1
2
3
4
5
6
Delay in treatment (hours) from hypotension onset
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Kumar, et al. Crit Care Med 2006;34:1589–1596
CAP – Complications
 Hypotension and septic shock
 3-5% Pleural effusion; Clear fluid + pus cells
 1% Empyema thoracis pus in the pleural space
 Lung abscess – destruction of lung .
 Single (aspiration) anaerobes, Pseudomonas
 Multiple (metastatic) Staphylococcus aureus
 Septicemia – Brain abscess, Liver Abscess
 Multiple Pyemic Abscesses
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IDSA: Outpt Management in Previously
Healthy Pt
• Organisms: S. pneumo, Mycoplasma, viral, Chlamydia pneumo,
H. flu
• Recommended abx:
– Advanced generation macrolide (azithro or clarithro) or doxycycline
• If abx within past 3 months:
– Respiratory quinolone (moxi-, levo-, gemi-), OR
– Advanced macrolide + amoxicillin, OR
– Advanced macrolide + amoxicillin-clavulanate
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IDSA: Outpt Management in Pt with
comorbidities
• Comorbidities: cardiopulmonary dz or immunocompromised
state
• Organisms: S. pneumo, viral, H. flu, aerobic GN rods, S. aureus
• Recommended Abx:
– Respiratory quinolone, OR advanced macrolide
• Recent Abx:
– Respiratory quinolone OR
– Advanced macrolide + beta-lactam
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IDSA: Inpt Management-Medical Ward
• Organisms: all of the above plus polymicrobial infections (+/anaerobes), Legionella
• Recommended Parenteral Abx:
– Respiratory fluoroquinolone, OR
– Advanced macrolide plus a beta-lactam
• Recent Abx:
– As above. Regimen selected will depend on nature of recent antibiotic
therapy.
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IDSA: Inpt Management-Severe/ICU
• One of two major criteria:
– Mechanical ventilation
– Septic shock, OR
• Two of three minor criteria:
– SBP≤90mmHg,
– Multilobar disease
– PaO2/FIO2 ratio < 250
• Organisms: S. pneumo, Legionella, GN, Mycoplasma,
viral, ?Pseudomonas
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IDSA: Inpt Management: Severe/ICU
• No risk for Pseudomonas
– IV beta-lactam plus either
• IV macrolide, OR IV fluoroquinolone
• Risk for Pseudomonas
– Double therapy: selected IV antipseudomonal beta-lactam (cefepine,
imipenem, meropenem, piperacillin/tazobactam), plus
• IV antipseudomonal quinolone
-OR-
– Triple therapy: selected IV antipseudomonal beta-lactam plus
IV aminoglycoside plus either
IV macrolide, OR IV antipseudomonal quinolone
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Switch to Oral Therapy
• Four criteria:
– Improvement in cough and dyspnea
– Afebrile on two occasions 8 h apart
– WBC decreasing
– Functioning GI tract with adequate oral intake
• If overall clinical picture is otherwise favorable, can
can switch to oral therapy while still febrile.
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Duration of Therapy
• Minimum of 5 days
• Afebrile for at least 48 to 72 h
• No > 1 CAP-associated sign of clinical instability
• Longer duration of therapy
If initial therapy was not active against the identified
pathogen or complicated by extra pulmonary infection
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Prevention
• Smoking cessation
• Vaccination per ACIP recommendations
– Influenza
• Inactivated vaccine for people >50 yo, those at risk for influenza
compolications, household contacts of high-risk persons and
healthcare workers
• Intranasal live, attenuated vaccine: 5-49yo without chronic
underlying dz
– Pneumococcal
• Immunocompetent ≥ 65 yo, chronic illness and
immunocompromised ≤ 64 yo
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Epidemiology of Pneumococcal Infection in
Immunocompromised Adults
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• Streptococcus pneumoniae remains a leading cause
of serious illness, including bacteremia, meningitis,
and pneumonia among adults in the United States.
• An estimated 4,000 deaths occur annually in USA
primarily among adults.
• For adults aged 18–64 years with hematologic cancer,
the rate of IPD in 2010 was 186 per 100,000, and for
persons with human immunodeficiency virus (HIV) the
rate was 173 per 100,000 (CDC, unpublished data,
2012).
• The disease rates for adults in these groups can be
more than 20 times those for adults without high-risk
medical conditions.
• PCV13 has been used for children since 2010, when it replaced
an earlier version targeting seven serotypes (PCV7; Prevnar,
Pfizer) that had been in use since 2000.
• The routine use of PCV7 in infants and young children resulted
in significant reductions in IPD caused by vaccine serotypes in
children, and because of indirect effects, also in adults.
• Rates of IPD caused by vaccine serotypes in adults aged 18–
64 years without HIV decreased from six cases to one case per
100,000 during 2000–2007.
• However, even after indirect effects of the pediatric
immunization had been realized fully, the incidence of IPD
caused by the serotypes included in PCV7 remained high in
HIV-infected persons aged 18–64 years at 64 cases per
100,000 persons with acquired immunodeficiency syndrome
(AIDS) .
• Moreover, 50% of IPD cases among immunocompromised
adults in 2010 were caused by serotypes contained in PCV13;
an additional 21% were caused by serotypes only contained in
48 PPSV23.
• In two randomized, multicenter immunogenicity studies
conducted in the United States and Europe,
immunocompetent adults aged ≥50 years received a
single dose of PCV13 or PPSV23.
• In adults aged 60–64 years and aged >70 years,
PCV13 elicited opsonophagocytic activity (OPA)
geometric mean antibody titers (GMTs) that were
comparable with, or higher than, responses elicited by
PPSV23.
• OPA GMTs elicited by PCV13 in adults aged 50–59
years for all 13 serotypes were comparable with the
corresponding GMTs elicited by administration of
PCV13 in adults aged 60–64 years.
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PCV13 Vaccine in Adults
• PCV13 was licensed by the Food and Drug Administration
(FDA) for prevention of IPD and otitis media in infants and
young children in February 2010, supplanting PCV7
• One dose of PCV13 is recommended by ACIP for children aged
6–18 years with high-risk conditions such as functional or
anatomic asplenia, immunocompromising conditions, cochlear
implants, or CSF leaks.
• In December 2011, FDA licensed PCV13 for prevention of
pneumonia and IPD in adults aged ≥50 years .
• Approval of PCV13 for adults was based on immunogenicity
studies that compared antibody responses to PCV13 with
antibody responses to PPSV23
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ACIP Recommendations for PCV13 and
PPSV23 Use
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• Pneumococcal vaccine-naïve persons.
• ACIP recommends that adults aged ≥19 years with
immunocompromising conditions, functional or
anatomic asplenia, CSF leaks, or cochlear implants,
and who have not previously received PCV13 or
PPSV23, should receive a dose of PCV13 first,
followed by a dose of PPSV23 at least 8 weeks later
(Table).
• Subsequent doses of PPSV23 should follow current
PPSV23 recommendations 5 years after the first
PPSV23 dose for persons aged 19–64 years with
functional or anatomic asplenia and for persons with
immunocompromising conditions.
• Previous vaccination with PPSV23.
• Adults aged ≥19 years with immunocompromising
conditions, functional or anatomic asplenia, CSF leaks,
or cochlear implants, who previously have received ≥1
doses of PPSV23 should be given a PCV13 dose ≥1
year after the last PPSV23 dose was received.
• For those who require additional doses of PPSV23,
the first such dose should be given no sooner than 8
weeks after PCV13 and at least 5 years after the most
recent dose of PPSV23
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CAP – So How Best to Win the War?
 Early antibiotic administration within 4-6 hours
 Empiric antibiotic Rx. as per guidelines (IDSA / ATS)
 PORT – PSI scoring and Classification of cases
 Early hospitalization in Class IV and V
 Decrease smoking cessation - advice / counseling
 Arterial oxygenation assessment in the first 24 h
 Blood culture collection in the first 24 h prior to Abx.
 Pneumococcal & Influenza vaccination; Smoking X
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Thank you
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