Pneumonia

Pneumonia is an infection of the pulmonary

parenchyma
Classification

Community acquired pneumonia

Nosocomial pneumonia
Hospital acquired pneumonia/Ventilator-associated
pneumonia (HAP/VAP)
Health care associated pneumonia (HCAP)
Aspiration pneumonia
Pneumonia in immunocompromised patient
Pathogenesis
Pneumonia results from the proliferation of microbial
pathogens at the alveolar level and the host's response to
those pathogens
Pulmonary Defense Mechanisms
Defense Impaired by
Non specific defense
Cough and gag reflex Alcohol, stroke, coma
Mucociliary elevator Alcohol, virus, smoking,
Kartagener's syndrome, cystic
fibrosis
Alveolar macrophages alcohol, virus, smoking, steroid,
pulmonary edema
Specific defense
Humoral Ig deficiencies, myeloma
Cell mediated Hodgkins lymphoma,steroids, HIV
Virulence Properties of Pathogens
Adhesion molecules that bind to cell receptors
HA of influenza binds sialic acid
G protein of RSV binds to glycoaminoglycans

Mechanisms to evade innate host defenses

NS1/2 proteins of RSV block -interferon
Virulence Properties of Pathogens
Ability to avoid adaptive immune mechanisms
IgA protease of pneumococcus
gene recombination by influenza
Production of toxins
capillary leak Hantavirus via -3 integrins
EF & LF toxins of B. anthracis
Pseudomonas type III protein, Exotoxin A
Evolution of antibiotic resistance
-lactamases by bacteria
amantadine resistance by influenza
Acquisition of Infection
1. Colonization of upper airway followed by
aspiration of a pathogen (S.pneumo)
2. Infection of upper airway and
inhalation/aspiration of infecting organism
(RSV, mycoplasma)
3. Direct lower airway inhalation of infecting
organism (Influenza, M.Tb,SARS CMV)
4. Hematogenous spread to lung (varicella,
E.coli)
 Pathophysiology
The host inflammatory response, rather than the proliferation of
microorganisms, triggers the clinical syndrome of pneumonia.
IL 1 and TNF fever
IL-8 and granulocyte colony-stimulating factor stimulate release
of neutrophils, migration to lung, producing both peripheral
leukocytosis and increased purulent secretions.
Inflammatory mediators alveolar capillary leak
Erythrocytes cross the alveolar-capillary membrane, with
consequent hemoptysis
 Pathophysiology
Capillary leak results in a radiographic infiltrate and rales
detectable on auscultation, and hypoxemia results from alveolar
filling.
Some bacterial pathogens interfere with hypoxic vasoconstriction
hypoxemia
Increased respiratory drive due to systemic inflammatory response
syndrome (SIRS) respiratory alkalosis.
Decreased compliance due to capillary leak, hypoxemia, increased
respiratory drive, increased secretions, and occasionally infection-
related bronchospasm dyspnea.
If severe enough, the changes in lung mechanics secondary to
reductions in lung volume and compliance and the intrapulmonary
shunting of blood may cause the patient's death
Pathology
Classic pneumonia evolves through a series of pathologic changes
(Pneumococcal Pneumonia)
Initial phase edema
presence of a proteinaceous exudateand often of bacteriain the alveoli.
This phase is rarely evident in clinical or autopsy specimens
Second stage - red hepatization phase
presence of erythrocytes and neutrophils in the cellular intraalveolar exudate
Bacteria are occasionally seen in cultures of alveolar specimens collected during this
phase.
Third phase- gray hepatization
no new erythrocytes are extravasating, and those already present have been lysed and
degraded.
neutrophil is the predominant cell, fibrin deposition is abundant, and bacteria have
disappeared.
corresponds with successful containment of the infection and improvement in gas
exchange.
Final phase- resolution
macrophage is the dominant cell type in the alveolar space, and the debris of
neutrophils, bacteria, and fibrin has been cleared, as has the inflammatory response.
Community acquired pneumonia
Common organisms
Streptococcus pneumoniae
Chlamydia pneumoniae
Mycoplasma pneumoniae
Legionella pneumoniae
Hemophilus influenzae
Uncommon organisms
Staph.aureus ( issue of MRSA)
Chlamydia psittaci
Coxiella burnetii
Klebsiella pneumoniae
Actinomyces
Viral (influenza, adenovirus, measles, RSV, varicella,
hantaviruses, metapneumoviruses, coronavirus )
Epidemiologic Factors Suggesting Possible Causes of
Community-Acquired Pneumonia
Factor Possible Pathogen(s)
Alcoholism Streptococcus pneumoniae, oral anaerobes,
Klebsiella pneumoniae, Acinetobacter
spp., Mycobacterium tuberculosis
COPD and/or smoking Haemophilus influenzae, Pseudomonas
aeruginosa, Legionella spp., S.
pneumoniae, Moraxella catarrhalis,
Chlamydophila pneumoniae
Structural lung disease (e.g., P. aeruginosa, Burkholderia cepacia,
bronchiectasis) Staphylococcus aureus
Dementia, stroke, decreased level of Oral anaerobes, gram-negative enteric
consciousness bacteria
Lung abscess CA-MRSA, oral anaerobes, endemic
fungi, M. tuberculosis, atypical
mycobacteria
Epidemiologic Factors Suggesting Possible Causes of
Community-Acquired Pneumonia
Travel to Ohio or St. Lawrence river Histoplasma capsulatum
valleys
Travel to southwestern United States Hantavirus, Coccidioides spp.
Travel to Southeast Asia Burkholderia pseudomallei, avian
influenza virus
Stay in hotel or on cruise ship in Legionella spp.
previous 2 weeks
Local influenza activity Influenza virus, S. pneumoniae, S.
aureus
Exposure to bats or birds H. capsulatum
Exposure to birds Chlamydophila psittaci
Exposure to rabbits Francisella tularensis
Exposure to sheep, goats, parturient cats Coxiella burnetii
Risk factors for CAP
Alcoholism
Asthma/COPD
Immunosuppression
Institutionalization
Advanced age
Clinical features
Symptoms
Cough
Fever, malaise
Pleuritic chest pain
Rusty sputum or sometimes blood stained
Confusion
Signs
Pyrexia, tachycardia, tachypnoea, SOB
Hypotension, confusion
Signs of pleurisy
Signs of consolidation
Pleural effusion
Clinical features atypical
Gradual onset, dry cough, SOB
Prominent extrapulmonary symptoms like-headache,
myalgia, sore throat, nausea, vomiting, diarrhoea
Erythema nodusum, myocarditis, pericarditis,
meningoencephalitis, rash, hemolytic anaemia, GBS in
Mycoplasma pneumonia
Hepatitis, hyponatraemia, hypoalbuminaemia, confusion
in legionella pneumonia
More radiological abnormalities despite less signs on
clinical examination
 How to Diagnose Pneumonia
Clinical history
Physical examination
& lab tests
Chest X-Ray
Investigations
Chest X-Ray:
In lobar pneumonia homogenous opacity 12-18 hrs
Opacity increases with appearance of air bronchogram
CXR - Can detect pleural effusion, abscess formation
(common with Staph aureus)
Patchy consolidation, hilar lymphadenopathy with
Mycoplasma pneumoniae
Follow up CXR to confirm resolution.
Failure of resolution indicates underlying bronchial obstruction
(foreign body or carcinoma)
Lobar Pneumonia :Most common causes for lobar pneumonia are:
Pneumococcus
Mycoplasma
Gram negative organisms
Legionella
Bronchopneumonia
Most common causes for bronchopneumonia are:
Streptococcus
Viral
Staph
Necrotizing Pneumonia
Most common causes for Necrotizing pneumonia are:
Staphylococcal
Anaerobic infection
Gram negative organisms
 A patient with aspiration lung abscess
Segmental Pneumonia
Most common causes for segmental pneumonia are:
Post obstructive
Aspiration
 CXR of a patient with Aspergillus Pneumonia
developed while on steroids.

Round Pneumonia
Most common causes for round pneumonia are:
Fungal
Tuberculous
 Pneumocystis Carinii pneumonia

Diffuse Alveolar Pneumonia

Most common causes for diffuse alveolar pneumonia are:
Pneumocystis
Cytomegalovirus
Diffuse Interstitial Pneumonia
Most common causes for diffuse interstitial pneumonia are:
Viral
Chickenpox
How to Diagnose Pneumonia
Clinical history
Physical examination
& lab tests
Chest X-Ray

? Enough for Therapy

Diagnostic
Microbiology
Microbiological examination
Severe community-acquired pneumonia
Sputum-Gram stain and culture, AFB stain
Blood culture
Serology for atypical organisms:acute and convalescent titres
to diagnose Mycoplasma, Chlamydia, Legionella and viral
infections. Pneumococcal antigen detection in serum
Microbiological examination
Severe community-acquired pneumonia
The above tests plus consider:
Tracheal aspirate, induced sputum, bronchoalveolar
lavage, protected brush specimen or percutaneous
needle aspiration. Direct fluorescent antibody stain for
Legionella and viruses
Serology-Legionella antigen in urine. Pneumococcal
antigen in sputum and blood. Immediate IgM for
Mycoplasma
Cold agglutinins-positive in 50% of patients with
Mycoplasma
Microbiological examination
Selected patients
Throat/nasopharyngeal swabs-helpful in children or during
influenza epidemic
Pleural fluid-should always be sampled when present in more
than trivial amounts, preferably with ultrasound guidance
Arterial blood gases (pulse oximetry)
may demonstrate hypoxia

Peripheral blood smear-

Leucocytosis, marginally or normal count
or leucopenia
Features associated with increased
mortality
Clinical Laboratory
Age 60 years Hypoxaemia: PaO2 <8kPa
Respiratory rate 30 /min Leucopenia <4000/mm3
Diastolic BP 60 mm Hg or Leucocytosis
Confusion
>20000/mm3
Raised serum urea
More than one lobe
involved in CxR >7mmol/L
Positive blood culture
Presence of underlying
disease Hypoalbuminaemia
Assessment of disease severity (CURB 65)
Cardinal markers of severity
Presence of Confusion
Blood Urea Nitrogen 7 mmol/L
Respiratory rate 30/min
Diastolic Blood Pressure 60mmHg

Age 65

If two or more features are present, there is 36 times

higher risk of dying
Differential diagnoses
Pulmonary infarction
Pulmonary tuberculosis
Pulmonary edema
Inflammatory disorders below the diaphragm
(liver abscess, perforated peptic ulcer, acute pancreatitis)
Management
1. Oxygen-high flow except in associated advanced COPD
2. Antibiotics should be started soon after diagnosis is
made (preferably after collection of the specimens)
3. Treatment of pleural pain
4. Physiotherapy
Antibiotic treatment
Uncomplicated CAP

Amoxicillin 500mg 8 hrly orally

If allergic to penicillin
Clarithromycin 500mg 12hrly orally or
Erythromycin 500mg 6 hrly orally or
Azithromycin 500mg/d

If staphylococcus is suspected
Flucloxacillin 1-2g iv 6hrly plus Clarithromycin 500mg 12 hrly i.v.

If mycoplasma or legionella is suspected

Clarithromycin500mg oral or i.v.or Erythromycin 500mg orally plus
Rifampicin 600mg 12 hrly orally or i.v.
Severe CAP
Clarithromycin 500mg 12hrly I.V. or
Azithromycin 500 mg iv stat then 250-500mg once
daily
plus
Co-amoxyclav 1.2g 12 hrly I.V.or
Ceftriaxone1-2 g aily I.V. or
Cefuroxime 1.5 g 8hrly I.V.or
Amoxycillin 1 g 6 hrly I.V. plus
flucloxacillin 2g 6 hrly I.V.
 Klebsiella-(if ESBL suspected)
Gentamicin plus either ceftazidime 1gm 8hrly or ciprofloxacin
200mg 12 hrly I.V.
Chlamydia
Erythromycin or tetracycline 500mg 6 hrly orally or 12 hrly I.V.
Actinomycosis
Benzyl penicillin 2-4 g 6 hrly I.V.

Duration of antibiotic treatment 7-10 days

Legionella, mycoplasma, staphylococcus for 14 days
Failure of resolution of symptoms
usually indicates.
Improper antibiotic
Mixed infection
Bronchial obstruction
Wrong diagnosis
Development of complication
Complications of pneumonia
Pleural effusion
Empyema
Lobar collapse
Lung abscess
ARDS, multi-organ failure
 Aspiration pneumonia, suppurative
pneumonia and lung abscess
Common in debilitated, comatose, heavy alcoholic or
patients who had undergone operation of nose, mouth,
throat under general anaesthesia or with laryngeal
paralysis
Aspiration of gastric or oropharyngeal contents
introduce organisms into the lungs
Lower lobes are mostly involved in aspiration pneumonia
Inflammatory process later on results into focal area of
parenchymal destruction and formation of
microabscesses.
 Large localized collection of pus or cavity lined by
granulation tissue, which ruptures into the bronchus is called
lung abscess
Primary bacterial pneumonia caused by Klebsiella and
Staphylococcus are also associated with pulmonary
suppuration (suppurative pneumonia) and lung abscess
Right sided endocarditis, commonly seen in IV drug
users,can result into multiple lung abscess.
 Patients present with fever, pleuritic chest pain and
cough with expectoration of large amounts of purulent
sputum.

On examination there may be digital clubbing, signs of

consolidation pleural rub

CXR-Large opacity which cavitates later on with

appearance of air fluid level indicates lung abscess
 Treatment should be targeted to the aetiological agent.
Amoxycillin 500 mg 6 hrly plus metronidazole 400 mg 8 hrly is
usually effective.
Clindamycin 600mg TDS till response then 300mg TDS to QID
Augmentin 825mg TDS
Treatment should be continued for 4-6 weeks in lung abscess
or till resolution of an abscess
Physiotherapy is of great value
Abscess not responding to medical therapy needs surgical
intervention.
Discharge
Discharge from hospital should only be contemplated
when patients are clinically stable with no more than one
of the following clinical signs:
temperature > 37.8C,
heart rate > 100/min,
respiratory rate > 24/min,
systolic BP < 90 mmHg,
SaO2 < 90%,
inability to maintain oral intake and abnormal mental status.
 Hospital acquired pneumonia
Occurs in 2-5% of all hospital admissions

A new pneumonia occurring at least 2 days after admission to

the hospital

Includes post operative pneumonia, aspiration pneumonia,

pneumonia occurring in debilitated and patients receiving
assisted ventilation
 DEFINITIONS
Hospital Acquired Pneumonia (HAP)
48 h after hospital admission (excluding an incubating infection)
Early onset HAP vs Late onset HAP

Ventilator Associated Pneumonia (VAP)

48-72 h after endotracheal intubation
Early onset VAP vs Late onset VAP

Health Care Associated Pneumonia (HCAP)

hospitalized in an acute care hospital 2days in preceeding 90
days;
nursing home or long-term care facility resident;
recent iv chemotherapy, or wound care within past 30 days
attended a hospital or hemodialysis clinic
 EPIDEMIOLOGY
15% of all hospital associated infection 2nd common nosocomial
infections worldwide
9 - 27% of all ICU acquired infection & > 50% of antibiotic prescribed
Mechanical ventilation risk by 6 - 21 times & incidence of VAP
increases with duration of ventilation
Risk of VAP highest early in the course of hospital stay
3%/day for first 5 days,2%/day from 5 to 10 days &
1%/day thereafter
Increases hospital stay (7-9 days/pt) & extra cost burden
($40,000/pt)
Mortality rate 24%-70% & Attributable mortality: 33-50%
Crude mortality rate >20 % if high risk pathogen involved .
Mortality in Pt with VAP twice than pts without VAP
At PGI there were 77 episodes of infection in 67 of the 201 patients.
Pneumonia was the most common infection (46/201 patients, 23%),
which constituted 59.7% of all nosocomial infections.
 FACTORS PREDISPOSING TO
NOSOCOMIAL PNEUMONIA
Reduced host defences against bacteria
Reduced immune defences (e.g. corticosteroid treatment, diabetes, malignancy)
Reduced cough reflex (e.g. post-operative)
Disordered mucociliary clearance (e.g. anaesthetic agents)
Bulbar or vocal cord palsy
Aspiration of nasopharyngeal or gastric secretions
Immobility or reduced conscious level
Vomiting, dysphagia, achalasia or severe reflux
Nasogastric intubation
Bacteria introduced into lower respiratory tract
Endotracheal intubation/tracheostomy
Infected ventilators/nebulisers/bronchoscopes
Dental or sinus infection
Bacteraemia
Abdominal sepsis
Intravenous cannula infection
Infected emboli
 Host Prior antibiotic Invasive Medications altering
factors therapy devices Gastric emptying and pH

Contaminated water source,

Colonization of medication solutions, respiratory-
aerodigestive tract therapy solutions

Aspiration Inhalation
ET tube (biofilm)

Transthoracic infection,
Primary bacteremia, Bronchiolitis
Possible GI translocation Host systemic
& LRT defense
Focal or multifocal mechanism
Secondary bacteremia bronchopneumonia
SIRS
Non pulmonary organ
Confluent bronchopneumonia
dysfunction

Lung abscess
MICROBIOLGY
Different spectrum than CAP

Different in different regions

Severe NP
Organisms depend on:
Admission to ICU
Time of onset (Early Vs Late)
Severity of illness
Respiratory failure (need of ventilator)
Presence of Risk factors
Rapid CxR progression

Evidence of sepsis or end organ

dysfunction
MICROBIOLGY

Mild/Moderate HAP with Early Severe HAP with risk

anytime onset, no risk factors Factors or late onset severe
or early onset severe HAP HAP
Enteric GNB Pseudomonas aeruginosa
Enterobactor species
E.coli Acinetobactor species
Klebsiella species
Proteus species MRSA
Serratia marcescens
H. influenzae
MSSA

S. pneumoniae

Am J Respir Crit Care Med 1995;153:1711-1725

Risk factors
Pathogens Risk factors
Anaerobes Abdominal surgery, aspiration, foreign body

S.aureus Coma, head trauma, DM, renal failure, iv drug abuse,

influenza
Legionella Corticosteroid, malignancy, neutropenia, chemotherapy,
renal failure, contaminated coolers/towers
Pseudomonas Long ICU stay, corticosteroids, underlying lung disease,
prior abx use
Aspergillus Immunocompromised pts, neutropenia, organ transplant
/Candida
Viruses Seasonal (Influenza, parainfluenza, adenovirus, RSV)

Am J Respir Crit Care Med 1995;153:1711-1725

 DIAGNOSIS OF HAP

Clinical + Chest X ray + Microbiology

New onset fever
Purulent expectoration
Tachycardia
Tachypnoea
Leukocytosis /
Leukopenia
Need of higher FiO2

Microbiology
Clinical diagnosis to identify etiology
high sensitivity, low specificity de-escalate therapy
empiric treatment decide duration of therapy
 METHODS

Proximal Airways Distal Airways

Sputum Non bronchoscopic Bronchoscopic
Tracheal aspirate

PSB PSB
BAL BAL
Protected BAL Protected BAL
Simple
No expertise required
Non-quantitative culture ADV: ADV:
high sensitivity Non invasive Proper sampling from
low specificity Low cost desired bronchus
NPV 93% for ETA <103 CFU/ml No expertise required Less contamination
Less complication
DISADV
DISADV: Hypoxia
Blind procedure Expertise
Sampling error Expensive
Empiric antibiotic therapy
HAP,VAP or HCAP suspected
(All Disease Severity)

Late onset or risk factors

for MDR pathogens

No Yes

Limited Spectrum Broad Spectrum

Antibiotic therapy Antibiotic therapy for
Shorter duration MDR Pathogens
Initial empiric therapy, no known risk factors for MDR
pathogens, early onset and any disease severity
Potential Pathogen Recommended Antibiotic
Streptococcus pneumoniae
Ceftriaxone
Haemophilus influenzae OR
Levofloxacin, moxifloxacin,
Methicillin-susceptible Staphylococcus aureus or ciprofloxacin
(MSSA)
OR
Ampicillin/sulbactam
Antibiotic-sensitive enteric
Gram-negative bacilli (EGNB) OR
Escherichia coli Ertapenem
Klebsiella pneumoniae
Enterobacter spp.
Proteus spp.
Serratia marcescens

Am J Respir Crit Care Med 2005;171:388416

Initial empiric therapy in patients with late onset or risk factors for
MDR pathogens, and any disease severity

Potential Pathogens Combination Antibiotic Therapy

Pathogens listed previously Anti-pseudomonal cephalosporin
(S. pneumoniae, H. influenzae, MSSA, (cefepime, ceftazidime)
antibiotic-susceptible EGNB) or
Anti-pseudomonal carbapenem
MDR pathogens (imipenem or meropenem)
P. aeruginosa or
K. pneumoniae ESBL -lactam/-lactamase inhibitor
(piperacillin/tazobactam)
Acinetobacter spp.
+
MRSA
Anti-pseudomonal fluoroquinolone
(ciprofloxacin or levofloxacin)
Legionella pneumophilia or
Aminoglycoside
(amikacin, gentamicin or tobramycin)
+
Linezolid or vancomycin
(if MRSA risk factors are present or there is a
high incidence locally)
Initial IV adult doses for empiric therapy of HAP, VAP, HCAP with
Late-0nset or risk factors for MDR pathogen

Antibiotic Dosage*
Antipseudomonal cephalosporin
Cefepime 1-2g every 8-12 hrs
Ceftazidime 2g every 8 hrs
Carbapenems
Imipenem 500mg every 6 hrs or 1g every 8 hrs
Meropenem 1g every 8 hrs
-lactam/ -lactamase inhibitor
Piperacillin-tazobactum 4.5g every 6 hrs
Cefoperazone-sulbactum 2g every 12 hrs
Aminoglycosides
Gentamicin 7mg/kg per day
Tobramycin 7mg/kg per day
Amikacin 20mg/kg per day

* Based on normal RFT/LFT

Initial IV adult doses for empiric therapy of HAP, VAP, HCAP with
Late-0nset or risk factors for MDR pathogen

Antibiotic Dosage*
Antipseudomonal quinolones
Levofloxaxin 750mg every day
Ciprofloxacin 400mg every 8 hrs

Vancomycin 15mg/kg every 12 hrs

Linezolid 600mg every 12 hrs

* Based on normal RFT/LFT

Pneumonia in Immunocompromised
patient
Causative organisms-pneumocystis jiroveci, pseudomonas,
aspergillus, cytomegalovirus,herpesviruses and mycobacteria
Gradual onset with fever, cough, breathlessness and infiltrate in the
chest X-ray.
Investigations include sputum examination, BAL, transbronchial
biopsy and in some cases open lung biopsy.
 Empirical treatment is a third generation cephalosporin or a
quinolone plus a anti staph antibiotic
or
Antipseudomonal antibiotic plus an aminoglycoside

Pneumocystis jiroveci responds to co-trimoxazloe or

pentamidine or atovaquone