Evidence based management of

community acquired Pneumonias

DR. S.K JINDAL

W W W. J I N D A L C H E S T. C O M
 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
 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

 Homeostasis - unbalanced in CAP
The germ is NOTHING… the soil is EVERYTHING…
Louis Pasteur 1895

Host defenses

Pathogens
 Management Issues

1. Presence of any Risk Factors?

2. What other organs are involved?

3. Which organism is likely? Is it drug-sensitive? Multiple organisms?

4. Antibiotic choice?

5. How long to continue?

6. Supportive therapy?

7. Future course- Resolution/ Complications/ Failure/ Mortality?

What is the evidence for each decision?

 Risk Factors

1. Increased incidence: COPD, DM, CHF, CAD, malignancies, ch. neurol or liver
disease, CRF

2. 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.

3. Modifying factors: Risk of inf. with drug resistance and unusual pathogens
 Age > 65 yrs, Alcoholism
  Lactam therapy within past 3 months
 Immunosuppression, Multiple comorbidities

Exposure/s to child in a day care centre

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

CXR (If available)

Yes No
Radiol. Features Present CRB-65 Score

Absent <1
>1
Oximetry
Consider alternate Dx Yes SaO2 < 92% (Age < 50)
or < 90% (age > 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)
 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)

 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
 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
 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 > 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
 “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
 Assessment of Severity

1. Routine Clinical Assessment

2. Host factors

3. General indicators: Fever, Leucocytosis, blood cultures, C Reactive

Protein

4. Clinical Scoring System

5. Micro organism pattern

6. Biomarkers
 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 > 30 bpm, DBP < 60 mm Hg, SBP < 90 mm Hg, HR > 125 bpm, fever

< 35o > 40o C, altered mental status and evidence of extrapulmonary sites of
infection
 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

 Criteria for risk stratification in CAP
CURB-65 CRB-65 ATS-IDSA criteria
Confusion Confusion Major criteria

Urea > mmol/L Invasive mechanical ventilation

Septic shock with the need for
Respiratory rate > Respiratory rate > 30 vasopressors
30/min min Minor criteria

Blood pressure (diastolic Low blood pressure Respiratory rate > 30

blood pressure < (diastolic blood PaO2/FiO2 ratio < 250
60mmHg or systolic pressure < 60mmHg or Multilobar infiltrates
blood pressure < systolic blood pressure Confusion/disorientation
90mmHg) < 90mmHg) Uremia (BUN level > 20 mg/dL)
Thrombocytopenia (platelet
Age > 65 years count < 100,000 cells/mm3)
Hypothermia (core temperature
Age > 65 years < 36oC)
 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)
 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).
 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.
 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
 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
 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

 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

 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)

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

 Fluoroquinolones (FQs) in CAP

1. 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)

2. Case-control study> Multiple FQs imparted

resistance to T.b. Long et al (2009)

3. Newer FQs appeared to mask active pulm TB

Chang et al. (2010)
 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)

 Rx of organism-documented CAP

Pathogen Preferred Alternative

Pneumococcus Amoxicillin or Penicillin G, Macrolides, cefuroxime
ceftriaxone
M. pneumoniae, C. Macrolides, Tetracyclines
pneumoniae, Legionella fluoroquinolones
H. influenzae Co-amoxiclav Cefotaxime, Ceftriaxone or
fluoroquinolone
Gram-negative enteric Cefuroxime, Cefotaxime, Fluoroquinolone or
bacilli ceftriazone carbapenems
Ps. aeruginosa Antipseudomonal β-lactam Antipseudomonal β-lactam +
+ aminoglycosides fluoroquinolones
S. aureus
Non-MRSA Cloxacillin Clindamycin
MRSA Vancomycin Teicoplanin
 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 (< 100 F) on two occasions 8 h

apart, WBC count decreasing, functioning GIT with adequate oral intake
 What is Clinical Failure?

 Death

 Need for mechanical ventilation

 RR > 25 / min

 SaO2 < 90%; PaO2 < 55 mmHg

 Hemodynamic instability

 Less than 1oC decline in admission temp. of > 38.5oC

 Altered mental state

 How to predict failure?

1. Routine Clinical Assessment

2. Host factors

3. General indicators: Fever, Leucocytosis, blood cultures, C Reactive

Protein

4. Clinical Scoring System

5. Micro organism pattern

6. Biomarkers
 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
 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
1. Complications: Effusion, empyema, cavitation, bronchiectasis
2. Comorbidities (Pulmonary / Non-pulmonary)
3. Systemic complications – Sepsis, Infective endocarditis
4. Non-infectious/Uncommon infectious etiologies
5. Other infections: TB, Fungal, Zoonotic
 Out-patients Recommendations

I. No cardiopulmonary disease / No disease modifying factors

 β-lactam, macrolide, doxycycline

II. Cardiopulmonary disease / disease modifying factors

 Beta lactam + macrolide (or doxy)

Fluoroquinolones should be used judiciously

 Inpatient Recommendations

I. Non-severe CAP
 β-lactam or macrolide

II. Severe CAP/No risk factor for Pseudomonas

 IV Beta lactam + azithromycin

III. Severe CAP/Risk factor for Pseudomonas

 IV anti-pseudomonal β-lactam + anti-pseudomonal fluoroquinolones
 IV antipseudomonal β-lactam + amino-glycoside + azithromycin

Fluoroquinolones should be used judiciously

 Recommendation for vaccination

1. 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).

 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

Hippocrates…
 Organisms Antibiotics
 Most aerobic and Penicillin G, β-lactam
anaerobic cocci and β-lactamase inhibitors
 Gram +ve, E. coli, Ampi., amoxicillin, β lactam
Proteus & β-lactamase inhibitors
 Staph aureus - Cloxacillin
 Ps aeruginosa - Carbapenems, piperacillin-
tazobactam, cefepime,
ceftazidime, ciprofloxacin,
aminoglycosides
 Anaerobes - Clindamycin, penicillin G +
metronidazole, carbapenems,
β-lacta and β lactamase
inhibitors
 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

 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

> 60 622.2

Overall 35.1
 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.

THANK YOU