Evidence based management of community acquired Pneumonias

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Evidence based management ofcommunity acquired
Pneumonias

• Dr. S.K JINdal
• www.jindalchest.com

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What is Pneumonia?

• Pneumonia Alveolar infection resulting from
  the invasion and overgrowth of microorganisms in
  lung parenchyma.
• Anatomical Lobar / segmental
• Bronchopneumonia
• Microbiological
• Empirical Community acquired
• Hospital acquired
• Aspiration
• Immuno compromised host
• Behavioural / therapeutic
• Easy / difficult
• Recurrent / complicated
• Persistent / resistant

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CLASSIFICATION OF PNEUMONIAS

• Community-acquired pneumonia - infection in a
  non-hospitalized population.
• Health-Care associated pneumonia (HCAP) is type
  of CAP.
• Pneumonia in the Immunosuppressed individuals.
• Hospital-acquired pneumonia - pneumonia 48 hours
  or more after admission, and was not incubating
  at the time of admission
• Ventilator-associated pneumonia - pneumonia that
  arises more than 48-72 hours after endotracheal
  intubation

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Homeostasis - unbalanced in CAPThe germ is
NOTHING the soil is EVERYTHING
Louis Pasteur
1895
Host defenses
Pathogens
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Management Issues

• Presence of any Risk Factors?
• What other organs are involved?
• Which organism is likely? Is it drug-sensitive?
  Multiple organisms?
• Antibiotic choice?
• How long to continue?
• Supportive therapy?
• Future course- Resolution/ Complications/
  Failure/ Mortality?
• What is the evidence for each decision?

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Risk Factors

• Increased incidence COPD, DM, CHF, CAD,
  malignancies, ch. neurol or liver disease, CRF
• Increased mortality DM, CAD, CHF, neurologic dis
  Immunosuppression,., active malignancies,
  increasing age, bacteraemia, leukopenia,
  hypotension, hypoxemia, altered mental status,
  tachypnea, aspiration pn., Gram ve inf.
• Modifying factors Risk of inf. with drug
  resistance and unusual pathogens
• Age gt 65 yrs, Alcoholism
• ? Lactam therapy within past 3 months
• Immunosuppression, Multiple comorbidities
• Exposure/s to child in a day care centre

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• Risk for enteric gram ve inf
• Recent antibiotic therapy
• Underlying cardiopulm dis
• Residence in a nursing home
• Multiple medical co-morbidities
• Risk for P. aeruginosa
• Structural lung dis
• BSA therapy for gt 7 days in the past month
• Corticosteroids (at least 10 mg predn/day)
• Malnutrition

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Grading (Modified GRADE System)

• Strength of recommendation A or B
• Quality of evidence, supporting the
  recommendation 1, 2 or 3
• Usual Practice Point (UPP) if evidence is
  inadequate or not documented
• Grade A Strong recommendation to do (or
  not,do) where the benefits clearly outweigh the
  risk (or vice versa) for most, if not all
  patients
• Grade B Weaker recommendation where benefits and
  risk are more closely balanced or are more
  uncertain

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Level of Evidence

• Level I High quality consistent results from
  well performed RCTs, or overwhelming evidence
  from well-executed observational studies with
  strong effects
• Level 2 Moderate quality evidence from
  randomized trials (that suffer from flaws
• in conduct, inconsistency, indirectness,
  imprecise estimates, reporting bias, or other
  limitations) Physiologic studies
• Level 3 Low-quality evidence from observational
  evidence or from controlled trials with several
  serious limitations

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Diagnostic algorithm

• Clinical features
• CXR (If
  available)
• Yes
  No
• Radiol. Features Present
  CRB-65 Score
• Absent lt 1
• gt1
• Oximetry
• Consider alternate Dx
  Yes SaO2 lt 92 (Age lt 50)
• or lt 90
  (age gt 50)
• No
• Admit Manage as OPD
  pt.
• CXR, Blood tests
• Bl. Gases, sputum
• Ist dose of antibiotic
• Decide or ICU/Non ICU adm.
• (ATS criteria)

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Role of diagnostic tests

• CXR, if feasible (1A)
• CT chest only in those with non-resolution or for
  assessment of complication (2A)
• Bl. Culture in hospitalized patients (2A)
• Sputum/BAL smear and culture for hospitalized
  patients (2A)
• Sputum for AFB (UPP)

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Chest radiographs

• False-negative
  False-positive Early in course
  Interstitial lung dis
• PCP pneumonia Vasculitis
• Miliary TB
  Atelectasis
• Dehydration CHF
• Neutropenia
  Pulmonary infarcts
• 
  Malignancies
• 
  Miscellaneous
• 
  

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General Laboratory Tests

• Leucocytosis (polymorphonuclear)
• Raised ESR
• Arterial blood gases
• S. electrolytes liver renal function tests
• Blood sugar
• H.I.V. serology
• Blood cultures
• Others

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Microbiological tests

• Blood culture - Positive in around 25 indicator
  of severity
• Sputum smear and culture - Rapid, inexpensive,
  variable sensitivity specificity
• Serology - Initial testing only if onset gt 7
  days, or severe or unresponsive to ?-lactams
• Legionella urine antigen - Highly specific
  sensitive intubated patients with severe disease

• NOT INDICATED in OUT-PATIENTS
• BUT ONLY in IN-PATIENTS

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Pulmonary Samples for Diagnosis

• Sputum / induced sputum
• Bronchoscopic
• - Washings
• - Bronchial / bronchoalveolar lavage
• - Biopsy (bronchial / TBLB)
• - Needle aspiration
• Transthoracic needle biopsy
• Transtracheal aspiration
• Pleural aspirate / biopsy
• Thoracoscopic specimens

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Assessment of Severity

• Routine Clinical Assessment
• Host factors
• General indicators Fever, Leucocytosis, blood
  cultures, C Reactive Protein
• Clinical Scoring System
• Micro organism pattern
• Biomarkers

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Markers of Severity

• Age over 65 yr
• Presence of coexisting illnesses such as COPD,
  bronchiectasis, malignancy, diabetes mellitus,
  CRF, CHF, chronic liver disease, alcoholism,
  malnutrition, cerebrovascular disease,
  postsplenectomy and history of hospitalization
  within the past year
• RR gt 30 bpm, DBP lt 60 mm Hg, SBP lt 90 mm Hg, HR
  gt 125 bpm, fever lt 35o gt 40o C, altered mental
  status and evidence of extrapulmonary sites of
  infection

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Clinical Assessment Scores

• CURB 65, CRB
• Pneumonia Severity Index (PSI)
• Apache scoring system (APACHE II)
• PIRO score
• SMART COP and SMRT-CO
• A-DROP
• Others Multivariate prediction model

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Criteria for risk stratification in CAP
CURB-65 CRB-65 ATS-IDSA criteria
Confusion Urea gt mmol/L Respiratory rate gt 30/min Blood pressure (diastolic blood pressure lt 60mmHg or systolic blood pressure lt 90mmHg) Age gt 65 years Confusion Respiratory rate gt 30 min Low blood pressure (diastolic blood pressure lt 60mmHg or systolic blood pressure lt 90mmHg) Age gt 65 years Major criteria Invasive mechanical ventilation Septic shock with the need for vasopressors Minor criteria Respiratory rate gt 30 PaO2/FiO2 ratio lt 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN level gt 20 mg/dL) Thrombocytopenia (platelet count lt 100,000 cells/mm3) Hypothermia (core temperature lt 36oC)
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Biochemical markers of Diagnosis/
Severity/Prognosis

• To aid diagnosis
• Procalcitonin
• C Reactive protein
• Leukocytosis
• Pro-inflammatory cytokines- Il 2, IL
  6, TNF a
• Indicators of prognosis
• PCT, Markers of coagulation
• As a guide to antibiotic therapy PCT
• Others Plasma cystatin CPlasma Cathepsin B
  Natriuretic peptides (NT-pro BNP, MR-pro ANP,
  BNP) Variant promoter of IL-6 (IL-6 174 GG
  genotype)

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Procalcitonin (PCT)

• Inflammatory biomarker
• Acute phase reactant primarily produced by liver
  in bacterial infections
• Inhibited by viral related cytokines
• Increased PCT help to identify patients who
• Benefit from antibiotics
• Increased risk of death
• PCT-guided group had significantly less
  antibiotic use and duration of therapy
• 
  (Christ-Crain et al 2006).

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How do the cytokine activation patterns and
biomarkers help?

• Influenced by micro-organisms (Facilitate only a
  broader understanding of host inflammatory
  response to micro-organism)
• Provide important information on diagnosis,
  severity and prognosis. Not predictive of either
  classification or failure.
• Not possible to score and classify severity on
  basis of biomarkers.

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Biomarkers What one expects?

• Additional, actionable information to
• Assist a rapid and reliable diagnosis
• Indication of prognosis
• Select patients for specific interventions
• Reflect the efficacy (or its lack) of specific
  interventions
• Warns of progression
• Exhibit a large amplitude of variation
• Shows consistent response to infectious stimuli
• (Rapid, easy and inexpensive)
• Povoa, 2008

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Management of CAP

• Anti-microbial therapy - Antibiotics
• Supportive symptomatic therapy
• Fever, Dehydration, Systemic
  symptoms
• Stabilization of severity parameters
• De-oxygenation, Organ
  failure, Shock
• Treatment of complications
• Empyema, Cavitation, BP
  Fistulae
• Management of drug-toxicities
• Preventive strategies

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Need for Pathogen detection

• No difference in length of hospital stay and
  30-day mortality between pathogen directed vs
  empirical broad spectrum antibiotic therapy
• 
  Van der Eerden et al, 2005
• To confirm the diagnosis
• To guide antibiotic choice
• To define antibiotic sensitivities
• To reduce adverse events
• To reduce costs
• For epidemiological information about new
  emerging pathogens

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Antibiotic Use

• Factors for Antibiotics use for empiric treatment
• The most likely pathogens
• Knowledge of local susceptibility patters
• Pharmacokinetics and pharmacodynamics of
  antibiotics
• Compliance, safety and cost of the drugs
• Recently administered drugs

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Antibiotics for CAP

• As early as possible
• more important in severe CAP (2A)
• In outpatient settings, tmt targeted to st.
  pneumoniae (1A)
• Stratification on basis of presence/absence of
  comorbidities
• Select antibiotics on basis of stratification
  (1A)
• Avoid fluoroquinolones (1A)
• Appropriate dose and duration (1A)
• Tetrocystine insufficient evidence (3B)

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Indications for empiric combination therapy in
CAP

• Presence of comorbid medical conditions
• Chronic heart, lung, liver or renal disease
• Diabetes mellitus
• Alcoholism
• Malignancies
• Use of antimicrobials within the previous 3
  months
• Severe CAP with or without comorbidities

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Fluoroquinolones (FQs) in CAP

• Meta-analysis of nine trials.Mean duration of
  delayed diagnosis and treatment of pulmonary TB
  in FQ prescription group was 19.03 days, the odds
  ration of developing fluoroquinolone-resistant M.
  tuberculosis strain was 2.7 (95 CI, 1.3 5.6)
  Chan et al (2011)
• Case-control studygt Multiple FQs imparted
• resistance to T.b. Long
  et al (2009)
• 3. Newer FQs appeared to mask active pulm TB
• 
  Chang et al. (2010)

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Doses of drugs used in CAP

• Drug Doses
• Amoxicillin 0.5-1 g thrice
  daily (PO or IV)
• Co-amoxiclav 625 mg thrice a
  day to 1 g twice daily (PO)/1.2 g thrice daily
  (IV)
• Azithromycin 500 mg daily (PO
  or IV)
• Cefriaxone 1-2 g twice daily
  (IV)
• Cefotaxime 1 g thrice daily
  (IV)
• Cefepime 1-2 g two or three
  times a day (IV)
• Ceftazidime 2 g thrice daily
  (IV)
• Piperacillin-tazobactam 4.5 g four times a day
  (IV)
• Imipenem 0.5-1 g three to four
  times a day (IV)
• Meropenem 1 g thrice daily (IV)

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Rx of organism-documented CAP
Pathogen Preferred Alternative
Pneumococcus Amoxicillin or Penicillin G, ceftriaxone Macrolides, cefuroxime
M. pneumoniae, C. pneumoniae, Legionella Macrolides, fluoroquinolones Tetracyclines
H. influenzae Co-amoxiclav Cefotaxime, Ceftriaxone or fluoroquinolone
Gram-negative enteric bacilli Cefuroxime, Cefotaxime, ceftriazone Fluoroquinolone or carbapenems
Ps. aeruginosa Antipseudomonal ß-lactam aminoglycosides Antipseudomonal ß-lactam fluoroquinolones
S. aureus Non-MRSA MRSA Cloxacillin Vancomycin Clindamycin Teicoplanin
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Duration of therapy

• Duration of therapy
• Pneumococcus, Gram negative bacteria - 7 to 10 d
• M. pneumoniae C. pneumoniae - 10 to 14 d
• Legionella, Pseudomonas, Staph. aureus 14 to 21
  d
• Switch to Oral Therapy
• Improvement in cough and dyspnea, afebrile (lt 100
  F) on two occasions 8 h apart, WBC count
  decreasing, functioning GIT with adequate oral
  intake

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What is Clinical Failure?

• Death
• Need for mechanical ventilation
• RR gt 25 / min
• SaO2 lt 90 PaO2 lt 55 mmHg
• Hemodynamic instability
• Less than 1oC decline in admission temp. of gt
  38.5oC
• Altered mental state

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How to predict failure?

• Routine Clinical Assessment
• Host factors
• General indicators Fever, Leucocytosis, blood
  cultures, C Reactive Protein
• Clinical Scoring System
• Micro organism pattern
• Biomarkers

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Causes of Clinical Failure

• Antimicrobial failure
• Patient noncompliance, improper dosing regimen,
  resistant pathogen, unusual or unsuspected
  pathogen
• Infectious complications
• Empyema, endocarditis, superinfection
• Incorrect diagnosis
• Malignancy, pulmonary embolism, other
  noninfectious etiologies

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Approach to Treatment-Failure

• Persistent fever, worsening dyspnea,
• Un-resolving pneumonia symptoms, continued
  disability
• Chest X-Ray
• Chest CT Bronchoscopy
  Lab tests Lung biopsy
• Exclude
• Complications Effusion, empyema, cavitation,
  bronchiectasis
• Comorbidities (Pulmonary / Non-pulmonary)
• Systemic complications Sepsis, Infective
  endocarditis
• Non-infectious/Uncommon infectious etiologies
• Other infections TB, Fungal, Zoonotic

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Out-patients Recommendations

• No cardiopulmonary disease / No disease modifying
  factors
• ß-lactam, macrolide, doxycycline
• Cardiopulmonary disease / disease modifying
  factors
• Beta lactam macrolide (or doxy)

Fluoroquinolones should be used judiciously
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Inpatient Recommendations

• Non-severe CAP
• ß-lactam or macrolide
• Severe CAP/No risk factor for Pseudomonas
• IV Beta lactam azithromycin
• Severe CAP/Risk factor for Pseudomonas
• IV anti-pseudomonal ß-lactam anti-pseudomonal
  fluoroquinolones
• IV antipseudomonal ß-lactam amino-glycoside
  azithromycin

Fluoroquinolones should be used judiciously
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Recommendation for vaccination

• Pneumococcal vaccine
• Routine use among healthy immun
  ocompetent
• adults for CAP prevention - not
  recommended (1A).
• May be considered in special populations
  at high risk
• for invasive pneumococcal disease
  (2A).
• 2. Influenza vaccination
• Should be considered in adults for
  prevention
• of CAP (3A).
• Smoking cessation should be advised for all
  current smokers (1A).

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High-risk groups for vaccination

• Pneumococcal disease
• Chronic cardiovascular, pulm, renal, or liver
  disease Diabetes mellitus, Cerebrospinal fluid
  leaks Alcoholism, Asplenia
• Immunocompromising conditions/medications
• Influenza
• Chronic cardiovascular or pulmonary disease
• Chronic metabolic disease (including diabetes
  mellitus)
• Renal dysfunction, Hemoglobinopathies
• Immunocompromising conditions/medications
• Compromised lung function or increased aspiration
  risk

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Hippocrates
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Organisms Antibiotics

• Most aerobic and Penicillin
  G, ß-lactam
• anaerobic cocci and
  ß-lactamase inhibitors
• Gram ve, E. coli, Ampi.,
  amoxicillin, ß lactam
• Proteus
  ß-lactamase inhibitors
• Staph aureus -
  Cloxacillin
• Ps aeruginosa -
  Carbapenems, piperacillin-
• 
  tazobactam, cefepime,
• 
  ceftazidime, ciprofloxacin,
• 
  aminoglycosides
• Anaerobes -
  Clindamycin, penicillin G
• 
  metronidazole, carbapenems,
• 
  ß-lacta and ß lactamase
• 
  inhibitors

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• Do Not Use a BOMB
• when a Bullet does the job
• The Bomb will certainly kill
• BUT the Bomb is..
• Not cost-effective
• More destructive
• Responsible for extensive collateral damage
• Accompanied with long lasting effects, including
  rebound and chain reactions.
• It is much wiser to Choose the
  Bullet correctly

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WHO mortality figures for lower respiratory tract
infections in India
Age group (years) No. of deaths per lakh population in 2008
15-59 6.2
gt 60 622.2
Overall 35.1

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SUMMARY

• Clinical diagnosis of pneumonia is important for
  early treatment decisions.
• Clinical scores constitute the most relevant
  criteria for prediction of clinical failure and
  to decide the site of care.
• Biomarkers may aid in diagnosis, help to decide
  the antibiotic duration and the prognosis.
• An appropriate choice of antibiotic/s
  significantly improves the outcomes.
• Cause of failure should be identified and
  appropriate treated.

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THANK YOU