Community Acquired Pneumonia ACCP Pulmonary Board Review

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Community Acquired PneumoniaACCP Pulmonary
Board Review

• Lawrence C. Mohr, M.D., F.A.C.P., F.C.C.P.
• Professor of Medicine
• Director, Environmental Biosciences Program
• Medical University of South Carolina

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Disclosure
I have no financial or commercial conflicts of
interest related to this presentation.
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Community Acquired Pneumonia

• Definition
• An acute infection of the pulmonary parenchyma
• Accompanied by the presence of an acute
  infiltrate on a chest radiograph, or auscultatory
  findings consistent with pneumonia
• Patient not hospitalized or residing in a long
  term care facility for gt 14 days before onset of
  symptoms.

Bartlett JG, et al. Clin Infect Dis
200031347-82.
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Community Acquired Pneumonia

• Epidemiology
• 6th leading cause of death in U.S.
• 5-6 million cases annually
• 500,000 hospitalizations per year
• 45,000 deaths per year
• Mortality 2-40
• Outpatientslt1
• Hospitalized 10-14
• ICU 30-40

Bartlett JG, et al. Clin Infect Dis.
200031347-382.
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Community Acquired Pneumonia

• Epidemiology (contd)
• Fewest cases in 18-24 yr group
• Highest incidence in lt5 and gt65 yrs
• Mortality is disproportionately high in patients
  gt65 yrs

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Community Acquired Pneumonia

• Risk Factors
• Age
• Alcoholism
• Smoking
• Immunosuppression
• Institutionalization
• Asthma steroid or bronchodilator use
• COPD steroid or bronchodilator use
• PVD
• Dementia

ID Clinics 199812723. / Am J Med 199496313
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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 consumed

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Case 1
42-year-old nonsmoking woman Fever, malaise,
diffuse muscular and joint aches and pains, and a
nonproductive cough x 24 h. Physical exam
flushed appearance, mildly ill Pulse 110/min,
BP105/65 mmHg, RR20/min, Temp39.4 C Chest
exam unremarkable Rest of exam was normal
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Case 1 (contd)
Given oseltamivir for presumed influenza Next
day, progressive confusion and agitation Brought
to the ED Physical Exam acutely ill, confused
and agitated Pulse 125/min, BP90/60 mm H,
RR35/min, temp 40C Basal crepitations
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Question 1 The most likely diagnosis is 1.
Influenza pneumonia 2. Pneumococcal pneumonia 3.
Legionellosis 4. Mycoplasma pneumoniae pneumonia
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Question 1 The most likely diagnosis is 1.
Influenza pneumonia 2. Pneumococcal pneumonia 3.
Legionellosis 4. Mycoplasma pneumoniae pneumonia
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Clinical Diagnosis of CAP

• There are no distinctive clinical features that
  are diagnostic for any specific microbial agent.
• Since clinical manifestations of CAP are not
  specific for various microbial agents, the need
  for improved diagnostic technology continues to
  be clinically relevant.

Fang G-D et al Medicine 1990 69307-316
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Community Acquired Pneumonia
Microbiology

• Strep. pneumoniae 20-60
• H. influenzae 3-10
• Chlamydia pneumoniae 4-6
• Mycoplasma pneumonaie 1-6

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Community Acquired Pneumonia
Microbiology

• Legionella sp 2-8
• Staph. aureus 3-5
• Gram negative bacilli 3-5
• Viruses 2-13

40-60 - NO ORGANISM IDENTIFIED 2-5 - TWO OR
MORE ORGANISMS
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Microbiology of Hospitalized CAP
S pneumoniae C pneumoniae Viral M
pneumoniae Legionella spp H influenzae G-ve
enterobacteria C psittaci Coxiella burnetii S
aureus M catarrhalis Other
0
5
10
15
20
25
30
Percentage of Cases
Data from 26 prospective studies (5961 adults)
from 10 countries. Data from 6 studies
Woodhead, Mass, 1998.
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Epidemiological Conditions and Related Pathogens
in CAP
Bartlett JG, et al. Clin Infect Dis.
200031347-82.
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Epidemiological Conditions and Related Pathogens
in CAP
Bartlett JG, et al. Clin Infect Dis.
200031347-82.
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Case 2

• 62-year-old man with bronchiectasis presents
  with a left lower lobe pneumonia
• Admitted to hospital 2 months ago for a
  similar illness. Treated with Moxifloxacin at
  that time.
• Chronic Rx bronchodilators prednisone 10 mg
  po daily

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Question 2

• The probability that this patient has a
  Gram-negative pathogen as the etiologic agent
  associated with his pneumonia is
• 1. 5
• 2. 10
• 3. 20
• 4. 50

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Question 2

• The probability that this patient has a
  Gram-negative pathogen as the etiologic agent
  associated with his pneumonia is
• 1. 5
• 2. 10
• 3. 20
• 4. 50

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Risk Factors for Gram-Negative Pneumonia

• 559 consecutive hospitalized patients with CAP
• 60 patients (11) had CAP due to GNB

Arancibia F, et al. Arch Intern Med 2002
1621849-58
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Incidence of Gram-Negative Bacteria According to
Number of Risk Factors Present
of Episodes

• 4 risk factors identified in MV analysis
• Probable aspiration
• Previous hospital admission
• Previous antibiotic Rx
• Presence of pulmonary comorbidity

No. of Risk Factors
Arancibia, F. et al. Arch Intern Med
20021621849-1858.
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Community Acquired Pneumonia

• Laboratory Tests
• CXR
• CBC with differential
• BUN/Cr
• Glucose
• Liver enzymes
• Electrolytes
• Gram stain/culture of sputum
• Blood cultures
• Pneumococcal Legionella urinary antigens
• Oxygen saturation / ABG

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Community Acquired Pneumonia

• Diagnostic Evaluation
• CXR
• Usually needed to establish diagnosis
• Prognostic indicator
• Rule out other disorders
• May help in etiological diagnosis
• Only 3 of outpatients and 28 of ER patients
  with suggestive signs and symptoms actually have
  pneumonia

J Chr Dis 198437215-25
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Community Acquired Pneumonia

• Usefulness of Gram Stain
• Good sputum samples obtained from 39
• 83 show one predominant morphotype

Adeel A. Butt, MD
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Community Acquired Pneumonia
Who should be hospitalized?
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Case 3

• Presentation
• 45 yo ? presents to ED
• Cough, dyspnea, recent flu-like illness followed
  by sudden onset of fever, weakness and cough
• History
• 10 pack-year smoker (0.5 x 20)
• Type 2 DM
• Examination
• HR 100, RR 24, BP normal, T, 38.5ºC, basal
  crackles
• Investigations
• Sa02 93, WBC 13.8 x 109/L
• urea 7.8 mmol/L (1.8 to 8.2),

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Question 3

• Based on this persons level of illness,
  what is the most appropriate next step?
• 1. Admit to hospital ward
• 2. Treat and send home
• 3. Order a chest CT scan
• 4. Consult infectious disease specialist

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Question 3

• Based on this persons level of illness,
  what is the most appropriate next step?
• 1. Admit to hospital ward
• 2. Treat and send home
• 3. Order a chest CT scan
• 4. Consult infectious disease specialist

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Applying the CURB-65 Rule

• Score 0 to 1 is associated with mortality rate
  of lt2
• Possibly suited for home management
• Patients with score of 2 are at intermediate
  risk of death (9)
• Consider for hospital therapy
• Patients with score gt2 have a high mortality
  rate (gt19)
• Managed in hospital as severe CAP

Any of Confusion Urea gt7 mmol/l Respiratory
Rate 30/min Blood pressure (SBP lt90 mmHg or DBP
60 mm Hg) Age 65 years
CURB-65 Score
0 or 1
2
3
Group 1 Mortality Low (1.5) (n324, died5)
Group 2 Mortality Intermediate (9.2) (n184,
died17)
Group 3 Mortality High (22) (n210, died47)
Treatment Options
Likely suitable for home treatment
Consider hospital supervised treatment Options
may include Short stay inpatient Hospital-super
vised outpatient
Manage in hospital as severe pneumonia Assess for
ICU admission especially if CURB-65 score 4 or 5
Defined as a mental test score of 8 or less, or
new disorientation in person, place or time. Lim
WS et al. Thorax. 200358377-82.
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PORT Severity Index

• Class I
• Age lt 50 0/5 co-morbid conditions normal or
  mildly deranged VS normal mental status
• Class II-V
• Points assigned based on above, 5 co-morbid
  conditions, 5 PE findings, 7 lab or X-ray findings

Fine MJ. NEJM 1997336243-50
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PORT Severity Index
STEP 1
STEP 2
Yes
Is the patient gt50 years of age?
Class II(?70 points)
Assign points for Demographic variables Comorbid
conditions Physical observations Laboratory and
radiographic findings
No
Does the patient have any of the following
coexisting conditions Neoplastic disease
congestive heart failure cerebrovascular
disease renal disease liver disease
Class III(7190 points)
Yes
Class IV(91130 points)
No
Yes
Does the patient have any of thefollowing
abnormalities Altered mental status pulse
?125/min respiratory rate ?30/min systolic
blood pressure lt90 mmHg temperature lt35ºC or
?40ºC
Class V(gt130 points)
No
Class I
Fine MJ et al. N Engl J Med. 1997336243-250.
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Adeel A. Butt, MD
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PORT Severity Index Risk Categories
Risk categories according to two validation
cohorts (38,039 inpatients and 2287 in- and
outpatients) Fine MJ et al. N Engl J Med.
1997336243-50.
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Community Acquired Pneumonia

• Considerations for ICU Admission
• RR gt 30
• PaO2/FiO2 lt 250, or PO2 lt 60 on room air
• Need for mechanical ventilation
• Multilobar involvement
• Hypotension
• Need for vasopressors
• Oliguria
• Altered mental status

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Community Acquired Pneumonia

• Management Principles
• Rational use of microbiology laboratory
• Pathogen directed antimicrobial therapy whenever
  possible
• Prompt initiation of therapy lt4 hr
• Decision to hospitalize based on prognostic
  criteria

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Treatment GuidelinesIDSA ,CIDS-CTS , ATS and BTS
CAP
Outpatient
Inpatient
Ward
ICU
No Pseudomonas Risk
Pseudomonas Risk
(Not BTS)
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Case 4
57-year-old man is admitted to the hospital with
2-day history of rigors, fever to 40C, cough
productive of purulent sputum and dyspnea. No
history of recent antibiotic therapy Physical
Examination Temp 40.2C, RR37/min,
Pulse122/min, BP 85/40 mm Hg decreased breath
sounds with egophony in the LULF bibasalar
crackles Lab WBC 32.3 x 109/L with bands Na
132, urea 9.6 ABGs on 30 PaO2 69 mm Hg, PaCO2
30 mm Hg, pH 7.37 Blood culture preliminary
report ve for Gram positive organisms
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Question 4

• At this point which of the following antibiotics
  would you choose?
• 1. Ceftriaxone
• 2. Moxifloxacin
• 3. Piperacillin/tazobactam amikacin
• 4. Ceftriaxone moxifloxacin

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Question 4

• At this point which of the following antibiotics
  would you choose?
• 1. Ceftriaxone
• 2. Moxifloxacin
• 3. Piperacillin/tazobactam amikacin
• 4. Ceftriaxone moxifloxacin

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ATS-IDSA Guidelines for Outpatient Treatment
CAP Outpatient Therapy
Previously Healthy
Recent antibiotic
No recent antibiotic
Respiratory Fluoroquinolone alone, or an
Advanced Macrolide ?-Lactam
Macrolide OR Doxycycline
Mandell LA, et al. Clin Infect Dis 2007.
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ATS-IDSA Guidelines for Outpatient Treatment
CAP Outpatient Therapy
Comorbidities
No recent antibiotic
Recent antibiotic
Respiratory fluoroquinolone alone or Advanced
macrolide ?-lactam
?-lactam macrolide or Respiratory
fluoroquinolone
Mandell LA, et al. Clin Infect Dis 2007.
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ATS-IDSA Guidelines for Outpatient Treatment
CAP Outpatient Therapy
gt25 high-level (MIC ? 16 g/mL) mac-resistant S.
pneumoniae
a Respiratory Fluoroquinolone
Mandell LA, et al. Clin Infect Dis 2007.
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ATS-IDSA Guidelines for Inpatient Treatment
CAP Inpatient Therapy
Medical Ward
Recent Antibiotic
No Recent Antibiotic
Respiratory Fluoroquinolone alone OR Advanced
Macrolide ß-Lactam
Advanced Macrolide ß-Lactam OR Respiratory
Fluoroquinolone alone
Regimen selected will depend on nature of
recent antibiotic therapy (Moxi, Levo 750)
Mandell LA, et al. Clin Infect Dis 2007
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ATS-IDSA Guidelines for Inpatient Treatment
CAP Inpatient Therapy
Intensive Care Unit
No Pseudomonas Risk
Pseudomonas Risk
No ß-lactam Allergy
ß-lactam Allergy
No ß-lactam Allergy
ß-lactam Allergy
ß-lactam Either Advanced Macrolide OR Respirator
y Fluoroquinolone
Respiratory Fluoroquinolone Aztreonam
Anti-pseudomonal, antipneumococcal b-lactam
/penem Cipro/Levo 750 OR Anti-pseudomonal,
antipneumococcal b-lactam /penem
Aminoglycoside Azithromycin
Aztreonam Respiratory Fluoroquinolone Aminogly
coside
Regimen selected will depend on nature of
recent antibiotic therapy (Moxi, Levo 750)
Mandell LA, et al. Clin Infect Dis 2007
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Combination Therapy in Severe CAP

• Prospective, multicenter observational study of
  844 adults with bacteremia due to S. pneumoniae
• Among critically ill patients, mortality
  significantly reduced 23.4 vs. 55.3, P0.0015

Baddour LM, et al. Am J Respir Crit Care Med.
2004170440-44.
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How Long Should You Treat?

• No good randomized controlled trials on which to
  base definitive guidelines
• Use experience and clinical judgment
• In general, the more severe the initial
  presentation, the longer the treatment course
  should be

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How Long Should You Treat?

• A generally accepted approach for outpatients and
  non-ICU inpatients
• S. pneumoniae, H. influenzae and other typical
  bacterial organisms (to include gram negative
  organisms) treat for 7 to 10 days
• Mycoplasma, Chalmydia and Legionella species
  treat for 10 to 14 days
• Influenza A (to include H5N1) and B
• Oseltamivir - 75 mg, PO, BID for 5 days
• Zanamivir 2 inhalations (2x5mg), BID for 5 days

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Switch To Oral Therapy

• As soon as possible after the patient is stable
  and shows signs of clinical improvement
• Criteria for switching to oral agents
• Improvement in cough and dyspnea
• Hemodynamically stable (Pulse lt 100, SBP gt 90
  mmHg)
• SaO2 gt 90 on room air
• RR lt 24 per minute
• Afebrile (lt37.8oC) on 2 occasions 8 hours apart
• Decreasing WBC
• Functional gastrointestinal tract
• Able to tolerate oral intake
• In general, most patients can be switched from IV
  to oral agents within 3 days

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Impact of Pneumococcal Bacteremia on Outcomes

• 125 pts. with pneumococcal bacteremic CAP were
  compared to 1,847 subjects with nonbacteremic CAP
• Multivariable regression analysis revealed a lack
  of association of bacteremic pneumococcal CAP
  and
• Time to clinical stability (hazard ratio HR,
  0.87 95 CI, 0.7 to 1.1 p 0.25)
• Length of hospital stay (HR, 1.14 95 CI, 0.91
  to 1.43 p 0.25)
• All-cause mortality (odds ratio OR, 0.68 95
  CI, 0.36 to 1.3 p 0.25)
• CAP-related mortality (OR, 0.86 95 CI, 0.35 to
  2.06 p 0.73).

Bordon, J. et al. Chest 2008133618-624
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Logistic Regression Analysis All-cause Mortality

• Pneumococcal bacteremic CAP did not increase the
  risk for all-cause mortality or CAP-related
  mortality
• The MRA revealed a lack of association of
  bacteremic pneumococcal CAP and all-cause
  mortality (odds ratio OR, 0.68 (95 CI, 0.36
  to 1.3 p 0.25)

Bordon, J. et al. Chest 2008133618-624
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Treatment Failure and Mortality According to
Adherence to Guidelines
Treatment Failure
Mortality
p0.03
p0.008
Menendez R et al. AJRCCM 2005 757-62
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Effect of Early Administration of Antibiotics on
Outcomes
Houck PM et al. Arch Intern Med 2004 164637-44
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Question 5

• All of the following statements are correct
  except
• 1. Macrolide resistance can be overcome by high
  doses of 2nd generation macrolides
• 2. Penicillin resistant strains of S.
  pneumoniae can be treated with high doses of
  ?-lactams
• 3. Bacterial resistance has been reduced by the
  introduction of new pneumococcal vaccines
• 4. Reduced susceptibility to penicillin
  predicts increased resistance to macrolides and
  3rd generation cephalosporins

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Question 5

• All of the following statements are correct
  except
• 1. Macrolide resistance can be overcome by high
  doses of 2nd generation macrolides
• 2. Penicillin resistant strains of S.
  pneumoniae can be treated with high doses of
  ?-lactams
• 3. Bacterial resistance has been reduced by the
  introduction of new pneumococcal vaccines
• 4. Reduced susceptibility to penicillin
  predicts increased resistance to macrolides and
  3rd generation cephalosporins

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Penicillin-Resistant S. pneumoniae in vitro is
Common1,2
S. pneumoniae resistance rate ()
Respiratory season

• 1. Alexander Project 19922000. Available at
  http//www.alexandernetwork.com. Accessed July
  11, 2006.
• PROTEKT US Study Report 2001-2004
  sanofi-aventis. Bridgewater, NJ, USA.

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Community Acquired Pneumonia

• Concerns About Penicillin Resistant
  Pneumococcus
• 25-40 overall penicillin resistance
• Intermediate resistance is of most clinical
  significance in elderly and immune compromised
  patients
• High level resistance (MIC gt 4) associated with
  in vitro macrolide and 3GC resistance
• Clinical failures local resistance patterns

IDSA guidelines Clin Infect Dis 200031347-82
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Impact of Penicillin Resistance on Mortality

• 10 studies involving 3430 pts
• mortality rate
• 19.4 in the PNSSP group
• 15.7 in the PSSP group
• RR of mortality for PNSSP vs. PSSP was 1.29 (95
  CI, 1.041.59) in 6 studies adjusted for age,
  comorbidities, and severity of illness
• ? relative risk of mortality when Rx was
  concordant or identical (RR 1.6)

Tleyjeh IM, et al. CID 200642788-797
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Increase in Macrolide-Resistant S. pneumoniae in
vitro1,2
S. pneumoniae resistance rate ()
Respiratory season

• Alexander Project 19922000. www.alexandernetwork.
  com
• PROTEKT US Study Report 20032004
  sanofi-aventis, Bridgewater, NJ, USA.

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Community Acquired Pneumonia
Macrolide Resistance

• Increased Drug Efflux
• Low level resistance
• Coded by mefE
• Susceptible to clindamycin
• Most cases in US
• Not overcome by standard or high doses of 2G
  macrolides

• Ribosomal Methylase
• High level resistance
• Coded by ermAM
• Resistant to clindamycin
• Mostly in Europe
• Not overcome by standard or high doses of 2G
  macrolides

Amsden GW. J Antimicrob Chemother 1999441-6.
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Fluoroquinolone Activity versus S. pneumoniae
Doern G, et al. Clin Infect Dis. 200541139-48.
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Community Acquired Pneumonia
Fluoroquinolones

• Active against 98 of penicillin resistant
  pneumococcus
• Resistance is increasing at different rates in
  different geographical areas
• Must be aware of local resistance patterns

Chen DK. NEJM 1999341233-9 Ho PL. Antimicrob
Agents Chemother 1999431310-3. Wise R. Lancet
19963481660
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Community Acquired Pneumonia

• Fluoroquinolone Resistance
• In a case control study, colonization or
  infection by FQ resistant pneumococci was
  independently associated with
• COPD
• Nosocomial origin of bacteremia
• Residence in a nursing home
• Prior exposure to FQ

Ho. Clin Infect Dis 200132701-707.
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Community-Acquired MRSA

• Severe, rapidly progressive, often necrotizing
  pneumonia
• Primarily has been associated with skin and soft
  tissue infections
• Frequently a history of preceding influenza-like
  illness
• All MRSA strains contain a mecA gene and
  regulatory sequences that produce
  penicillin-binding protein 2a
• Resistant to all ?-lactams including
  cephalosporins, cefamycins and carbapenems

Francis JS, et al. Clin Infect Dis. 2005 40
100-7
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Community-Acquired MRSA

• Cytotoxin called Panton Valentine Leukocidin
  (PVL) associated with primary skin infections
  and severe necrotizing pneumonia
• creates lytic pores in the cell membranes of
  PMNLs
• induces release of PMNL chemotactic factors
• For toxin-producing strains, antibiotics that
  inhibit protein synthesis (linezolid or
  clindamycin) may be better than vancomycin
• Concern of inducible clindamycin resistance has
  discouraged its use among clinicians
• Vancomycin is drug of choice for non-toxin
  producing MRSA bacteria - does not inhibit the
  production of the toxic PVL cytotoxin

Micek ST et al. Chest 2005 1282732-8
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Question 6
Which of the following statements about
pneumococcal vaccine is correct? 1. The 7 valent
conjugate vaccine does not affect invasive
pneumococcal disease in children 2. The 7 valent
conjugate vaccine does not affect invasive
infections with penicillin-resistant strains 3.
A second dose of the 7 valent conjugate vaccine
should be administered in 5 years to individuals
less than age 65 who received the first dose
before age 65 4. Prior polyvalent pneumococcal
vaccine has no impact on survival among adults
admitted to hospital with CAP
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Question 6
Which of the following statements about
pneumococcal vaccine is correct? 1. The 7 valent
conjugate vaccine does not affect invasive
pneumococcal disease in children 2. The 7 valent
conjugate vaccine does not affect invasive
infections with penicillin-resistant strains 3.
A second dose of the 7 valent conjugate vaccine
should be administered in 5 years to individuals
less than age 65 who received the first dose
before age 65 4. Prior polyvalent pneumococcal
vaccine has no impact on survival among adults
admitted to hospital with CAP
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Community Acquired Pneumonia Prevention

• Pneumococcal Polysaccharide Vaccine
• All adults gt 65 years of age
• Younger adults with
• Diabetes, cardiovascular disease, lung disease,
  alcohol abuse, immune system disorders, sickle
  cell disease, nephrotic syndrome, HIV infection,
  hematological malignancies, long-term
  immunosuppressive medication
• A second dose is recommended after 5 years for
  persons
• Age lt 65 who received first dose before age 65
• Immune system disorders

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Hennesy TE, et al. Vaccine 23 (2005) 54645473
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Question 7

• Which of the following statements is true for
  H5N1 avian or swine influenza?
• 1. Mainly transmitted from animals to humans
• 2. Easily transmitted from human to human
• 3. Prevented by influenza vaccination
• 4. Requires travel exposure in Asia

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Question 7

• Which of the following statements is true for
  H5N1 avian or swine influenza?
• 1. Mainly transmitted from animals to humans
• 2. Easily transmitted from human to human
• 3. Prevented by influenza vaccination
• 4. Requires travel exposure in Asia

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Influenza A Viral Architecture

• Hemagglutinin binds the virus to the target
  epithelial cell receptor
• Neuraminidase degrades the receptor, permitting
  the virus to enter the cell

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Community Acquired Pneumonia Prevention

• Influenza Vaccination
• All persons age 50 and older
• Persons of any age
• Residing in a nursing home
• Chronic cardiovascular disorder
• Chronic pulmonary disorder
• Diabetes mellitus
• Renal dysfunction
• Immmunosuppression
• Women in second trimester of pregnancy during flu
  season

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Summary

• S. pneumoniae remains the most important pathogen
  in the etiology of CAP
• Several tools help identify high risk candidates
• Use antibiotics judiciously and early (lt4hrs)
• Revise antibiotic therapy based on clinical and
  microbiological response
• Consider prior exposures and prior therapy when
  choosing antibiotics

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Summary

• Bacterial resistance is prevalent, and local
  rates of resistance should be considered when
  selecting antimicrobial therapy
• Guidelines improve outcomes
• Beware of emerging threats such as H5N1 influenza
  and CA-MRSP
• Pneumococcal vaccine reduces invasive
  pneumococcal disease and mortality from CAP in
  both children and adults

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Thank You !