PNEUMONIA (I)

Elisabeta Badila
The importance of the problem

 Important cause of morbidity and mortality

 Third cause of mortality in the world

 First cause of infectious mortality

 Every 2 minutes, 2 children die from pneumonia

 A significant percentage of patients require hospitalization

Definition

 Pathological
 Infection of alveoli, distal airways &
pulmonary interstitium 

 Clinical
 Constellation of symptoms and signs in
combination with at least one opacity on
chest X-ray
 I. Classification (etiology)
Gram + S. pneumoniae, Stafilococcus spp., Streptococcus spp.
Klebsiella pneumoniae, Escherichia coli, Enterobacter spp, Serratia
Gram - spp, Proteus spp, P. aeruginosa, Acinetobacter spp, Moraxella
Bacteria catarrhalis
Anaerobic
Mycobacteria
Infectious

Influenza, Parainfluenza, Respiratory syncytial virus, Adenovirus,

Viruses Human metapneumovirus, Rhinovirus, Varicella Virus, Measles Virus,
Hantavirus, Enterovirus
Legionella spp, M. pneumoniae, C. pneumoniae, and Chlamydia
Atypical microorganisms
psittaci

Histoplasma capsulatum, Coccidioides spp, Blastomyces

Fungi
dermatitidis, Aspergillus spp, Pneumocystis jirovecii

Aspiration
ous
II. Classification (anatomical)

 Lobar pneumonia

 Bronchopneumonia

 affects one or more lobes

 Interstitial pneumonia

 Miliary pneumonia
Interstitial pneumonia

 Diffuse bilateral interstitial and/or interstitial-alveolar

(mixed) infiltrates
 Inflammatory process predominantly in interstitium,
including the alveolar wall and connective tissue around
the bronchial tree

 Inflammation - segmental or diffuse

 Most commonly caused by viruses and M. pneumoniae

Miliary pneumonia

 In patients with impaired immune function / AIDS

 M. tuberculosis, Histoplasmosis, Coccididomycosis,

Herpes viruses, Cytomegalovirus, Varicella V.

 Discrete and numerous lesions resulting from the

hematogenous spread of germs

 Various tissue reactions – granulomas, caseous

necrosis
III. Classification (pathogenic)

 Primary

 Secondary

 Metastatic
IV. Classification

I. Community acquired pneumonia (CAP)

 Treated in outpatient / requires hospitalization (40-60%)

II. Hospital Aquired Pneumonia

 Hospital-Acquired Pneumonia (HAP)

 Ventilator-Associated
 
Pneumonia (VAP)
 Health Care Associated Pneumonia (HCAP)
Pathogenesis (I)
 Microaspiration of oropharyngeal secretions
 Main mechanism

 Streptococcus pneumoniae, Haemophilus infl.

 Macroaspiration
 Any alteration in level of consciousness (eg, stroke, seizure,
anesthesia, drug or alcohol intoxication); dysphagia due to
esophageal lesions and motility problems.
 Anaerobic, Gram negative
Pathogenesis (II)
Inhalation of infected aerosols
 M. tuberculosis, endemic fungi (Coccidoides, Blastomyces,
Histoplasma), Influenza, Legionella, Coxiella burnetii

Hematogenous spread
Intravenous catheters, septic thrombophlebitis, drug addicts, infectious
endocarditis, other infections (UTI)
MRSA (catheters, endocarditis), E. coli (UTI)

Direct spread
Traumatic, iatrogenic, contiguous focus
Defense mechanisms
 Lungs  area ~70 m2 exposed to particulate material and microbes
that are present in the upper airways
 Host defences
 innate – nonspecific / acquired – specific
 Mechanical
 anatomical features of upper airways, nasal nibs, cough, sneezing, mucociliary transport
(ciliary cells, mucus - contains mucin which incorporates microorganisms)
 Secretion
 nonspecific - lysozyme, lactoferrin, transferin 
 microbial anti-adhesion - fibronectin, surfactant 
 specific - Ig, complement
 Cellular  
 nonspecific - local alveolar macrophages, macrophages mobilized by inflammation  
 specific - cytokines, B and T lymphocytes
Contributing factors to the alteration of defense mechanisms
 Smoking, Pollution
  to C
 Age (childhood, very elderly)
 Alcoholism
 Dismicrobism - antibiotherapy, ICU
 Stasis in pulmonary circulation - HF
 Airways obstruction
 Impairment of immunity:
 Debilitating diseases – diabetes mellitus, chronic liver disease, CKD, neoplasia, nephrotic
syndrome
 Immunodepression - AIDS, lymphoma
 Iatrogenic immunosuppression – systemic cortisone, cytostatics, immunosuppressants
COMMUNITY
ACQUIRED
PNEUMONIA (CAP)
Epidemiology

 Incidence ~ 6 cases/1000 persons/year – in adults

 Prevalence
 Increases with increasing age, especially in men
 Seasonal variation  more cases  winter months

 40-60% requires hospitalization

 Mortality is higher for CAP patients who require hospitalization.
 ½ deaths - related to pneumonia, ½ comorbidities
 death - frequently in the first week
Risk factors for CAP
 Older age > 65 y.o.
 Chronic lung disease
 Conditions that increase risk of macroaspiration of stomach contents and / or
microaspiration of upper airway secretions: any alteration in level of consciousness
 Immunocompromising conditions: diabetes mellitus, HIV infections, immunosuppressive
medication use, neoplasia, malnutrition.
 Lifestyle factors: smoking, alcohol, toxic inhalations, homelessness
 Chronic diseases: heart failure, chronic kidney disease (CKD)  dialysis, cirrhosis
Pneumonia severity Pathogens

Prevalence of pathogens
Treated in outpatient - CAP
Streptococcus pneumoniae
1.
Mycoplasma pneumoniae
2.
3. Chlamydia pneumoniae
4. Haemophilus influenzae
Pathogenic agents
5. Inluenza viruses Frequency
6. Pneumocystis
Streptococcus Pneumoniae 20-60%
Requires 1. Streptococcus pneumoniae
Mixed etiologies
Haemophilus Infl. 2. 3-10%
hospitalization 3.
4.
Viruses
Haemophilus influenzae
Staphilococcus aureus
5. Chlamydia pneumoniae 3-5 %
6. Legionella
Gram negative 7. Mycoplasma pneumoniae 3-10%
8. Staphyloccocus aureus
Aspiration 9. Moraxella catarrhalis 6-10%
10. Gram negative aerobic bacillus
Others 11. Mycobacterium tuberculosis3-5 %
12. Pneumocystis
Legionella spp. 1. Streptococcus pneumoniae 2-8 %
Treated in ICU 2. Staphyloccocus aureus
Mycoplasma pneumoniae
3. Viruses 1-6 %
4. Mixed etiologies
Chlamidia pneumoniae
5. 4-6 %
Gram negative aerobic bacillus
6. Legionella
Viruses 7. Mycoplasma pneumoniae 2-15 %
8. Pneumocystis
The orientative etiology of CAP in terms of history and
physical examination

Medical staff Mycobacterium tuberculosis

Veterinarians, farmers, Coxiella burnetti
slaughterhouse workers
Bronchiectasis Pseudomonas aeruginosa
COPD S. pneumoniae, Haemophilus infl, Moraxella
Diabetes S. pneumoniae, S. aureus

Alcoholism S. pneumoniae, Klebsiella, S. aureus, anaerobes, Acinetobacter

Solid organ S. pneumoniae, Haemophilus, Legionella, Pneumocystis, CMV,

transplantation Strongyloides stercoralis

HIV S. pneumoniae, Pneumocystis, Haemophilus infl, Criptoccocus

neoformans, M. tuberculosis
Pathogenesis
  virulence +  defence (transient or chronic)

 alveolar exudate  rapid proliferation  infected exudate extention to

nearbording alveoli bronchi  other territories (in hours !!)   exudates
 early lymphatic drainage  bacteriemia (15-30% !!)  septic metastases
  gas exchange
 dispneea:
  stiffness
  pulmonary compliance, VC, FRC, TLC
 V/Q imbalance and intrapulmonary shunts with hypoxemia & hypo /
hypercapnia
Pathology
 tipically multisegmentar or lobar
 ~ 30% - multilobar

4 stages - simultaneously:
I - congestion
II - red hepatisation
III - gray hepatisation
IV – resolution
Diagnostic

Clinically Infiltrate on
compatible chest
syndrome radiograph
Microbiological
testing
for
hospitalised
Symptoms
 Severity
 Mild
 Fulminant and fatal, even in previously healthy subjects
 Onset
 Suddenly, dramatically / insidious

 ~ 50% of patients - preceded by upper RTI

 Typical (but unspecific) manifestations
Symptoms
Symptoms
 rare occurrence

headache,
nausea, diarrhea myalgia
vomiting arthralgia

confusion
asthenia
in elderly
 Egophony = an increased resonance of voice sounds heard
when auscultating the lungs
Physical exam Whispered pectoriloquy = increased loudness of whispering
noted during auscultation with a stethoscope on the lung
fields on a patient's torso.

Fever Egophony,
Tachypnea whispered
(~ in 80% pts,
absent in elderly) pectoriloquy

Consolidation Pleural
syndrome friction

Tachypnea > 30 / min in a person without known pulmonary disease - the most
useful clinical sign of severity!
Physical exam
 General appearance
 General altered state
 Warm and wet skin
 Labial or nasal herpes (> 10%)
 Ipsilateral cheek erythema
 Jaundice
 Cardiovascular
 Tachycardia, hypotension, collapse
 Septic sock
 Consolidation syndrome

 Expansion of the thorax on inspiration is reduced on the

affected side
 Vocal fremitus is increased on the affected side
 Percussion is dull in the affected area
 Medium, late, or pan-inspiratory  crackels
 Vocal resonance is increased – whispered pectoriloquy,
egophony
 A pleural rub may be present
Imaging – Chest X-ray

 Role:
 as a screening tool for the detection of new infiltrates
 for monitoring response to therapy
 enhanced ability to assess the extent of disease
 to detect complications
 i.e. cavitation, abscess formation, pneumothorax, pleural
effusion
 to detect additional or alternative diagnoses

 
Chest X-ray

- “gold standard” = presence of infiltrate

- does not have 100% specificity
- rarely provide etiological information
- eg, pneumatoceles
- in patients with HF or pulmonary fibrosis -
radiological diagnosis is difficult
Chest X-ray

 Lobar consolidation  ”typical" bacteria

 lobar pneumonia appears in the periphery abutting against the
pleura and spreads towards the core portions of the lung

 Interstitial infiltrates  “atypical" germs, viruses

 Cavitation

 Chest X-ray - can not differentiate a bacterial pneumonia

from a non-bacterial!
 Sometimes – false-negative results (volume depletion)!
Imaging - High-resolution CT
Role:
 Patients with signs and symptoms suggestive of pneumonia but with
negative chest X-ray
 Bilateral lesions
 Interstitial disease
 Cavitation, empyema
 Hilary adenopathy
 Patients not responding to treatment
 Suspicion of complications
Ultrasound exam
 Can detect the pulmonary changes associated with pneumonia as long as the
process involves some of the outer (non-mediastinal) pleural surface
 The ultrasound changes vary depending on the degree and extent of consolidation
process
 The appearance of frank consolidation looks remarkably liver-like and is also
termed hepatization
 Echogenic debris within the effusion can suggest empyema
Identification of the pathogen
 Cultures of sputum
 > 25 leukocytes and <10 squamous epithelial cells / campus
 smear / sputum – diplo  pneumococcus
 Correlation smear - culture
 Sputum isolates - sure pathogens: M. tuberculosis, Legionella, Histoplasma

 Blood cultures
 Positive to ~ 20%
 Mandatory at t < 36 °C or > 38.5 °C; social cases; alcoholics
 Frequently + for S. pneumoniae, Staph. aureus, E. coli

 Cultures from the pleural fluid

Microbiological diagnosis

 Antigen detection in urine

 Streptococcus pneumoniae
 by ELISA method
 high specificity and sensibility for those with bacteremia
 detection up to one month from onset; result in 15 min

 Legionella pneumophila
 serogroup 1 - urine detection by ELISA - severity of the disease
 the most commonly diagnostic method for legionellosis
 !!! other Legionella species - negative reaction
Identification of the pathogen
 Endotracheal secretions - bronchial brushing / bronchoalveoar lavage
 This method has proved particularly useful in the diagnosis of Pneumocystis pneumonia in AIDS
patients, providing an aetiological diagnosis in > 95% of cases

 Lung tissue biopsy

 IgM response
 Increase 4-fold the Ab titer against an Ag detected in urine, serum or pleural fluid
 Positive test for: M. pneumoniae, C. pneumoniae, Chlamydia psittaci, Legionella spp, C. burnetii,
adenoviruses, Influenza A, parainfluenza v.

 Methods of amplification of DNA or RNA

 Legionella spp, M. pneumoniae, C. pneumoniae; expensive investigation; not routine
 Complications
 Infectious complications  Imunological
 Pleural empyema
 Serofibrinous pleural effusion
 Necrotising pneumonia
 Glomerulonephritis
 Lung abcesses
 Atelectasis
 Overlap infection Respiratory insufficiency  Rare complications
Heart failure decompensation • Jaundice
 Late resolution
Shock
 Purulent pericarditis • Gastric dilatation
Arrhythmias
 Endocarditis Gastrointestinal bleeding
• Ileus paralytic
 Meningitis Kidney failure
• Deep vein thrombosis
 Septic arthtritis

!!! Only 30% of hospitalized patients have no complications

Diferential diagnosis
Chest radiograph with pathological changes Normal chest radigraph
Heart failure Exacerbation of COPD
Pulmonary infarction Flu
Radiation pneumonitis Acute Bronchitis
Atelectasis Pertussis
Vasculitis Asthma with viral infection
Exacerbation of bronchiectasis
Acute eosinophilic pneumonia
Cocaine-Induced Pulmonary Disease ("Crack
Lung")
Pulmonary / metastatic cancer
Pneumonia of hypersensitivity
PREDICTORS OF MORTALITY

Pneumonia Severity
Index (PSI)

Predict 30-day mortality

Pneumonia Severity Index (PSI)

Deaths

Points Risk Class Nursing Recommendation

Adults with
home pts
CAP
with CAP
<51 Low I 0.2% 0
51-70 Low II 0.5% 0 Outpatient
71-90 Low III 2.6% 4.8%
91-130 Moderate IV 9.3% 12%
Inpatient
>130 High V 24.9% 32.9%
PREDICTORS OF MORTALITY - CURB-65
 Confusion
 Urea > 20 mg/dl (7 mmoli/l)
 Respiratory rates > 30/min
 DBP < 60 mmHg or SBP < 90 mmHg
 Age > 65 y.o
0-1 Outpatient
2-3 Short stay in hospital /
 Mortality
monitor closely as
- 2,4% - 0 criteria
an
- 8% - 1 criteria - 33% - 3 criteria outpatient
- 23% - 2 criteria - 83% - 4 criteria
4-5 Hospitalization/ICU
 ATS 2001 – Am J Resp Crit Care Med, 163:1730-1754
Ewig et al. Am J Resp Crit Care Med, 158: 1102-1108
IDSA/ATS Severity Criteria

Category Criteria

Major 1. Requirement for mechanical ventilation

2. Septic shock requiring vasopressor support

Minor 1. RR > 30/min

(≧ 3 criteria) 2. SBP < 90 mmHg & DBP < 60 mmHg
3. PaO2/FIO2 (fractional inspired oxygen) < 250
4. Multilobar infiltrates
5. Confusion
6. Blood urea nitrogen ≥ 20 mg/dl (blood urea 7 mmol/L)
7. Leukopenia
8. Thrombocytopenia
9. Hypothermia
10. Hypotension requiring fluid support
CAP – hospital admission criteria
Respiratory Frequency > 30 / min

SBP < 90 mmHg or 30 mmHg below basal level

Confusional state or altered consciousness

Hipoxemia – PO2 <60 mmHg or SO2 <90%

Comorbidities: HF, diabetes, alcoholism, immunosuppression

Multilobar pneumonia with associated hypoxemia

Parapneumonic pleural effusion that requires fluid analysis

Principles of treatment
Pneumonia

Outpatient Inpatient

1 antibiotic
if it does not exist Non ICU ICU
associated RF

1/2 2/3
antibiotics antibiotics
Antibiotics Classes
 Beta-lactams
 not on atypical
 efficiency on DRSP
 Macrolides
 cover atypical germs
 ineffective in DRSP
 Fluorquinolone
 Aminoglycosides "Atypical“ germs: Legionella
spp,
 anti MRSA M. pneumoniae,
Chlamydia pneumoniae, C. psittaci
DRSP=drug resistant Strept. pneum
 The empirical antibiotic therapy Ou
tpa
tie
Medicare Study nt

Previously healthy + no use of AB within the previous Presence of comorbidities

3 months: Use of AB within the previous 3 months:
↓ ↓
Macrolide A respiratory fluoroquinolone
(azithromycin, clarithromycin, or erythromycin) (moxifloxacin, gemifloxacin, or levofloxacin)
OR OR
Doxycyline A beta-lactam
(first-line agents: high-dose amoxicillin, amoxicillin-
clavulanate; alternative agents: ceftriaxone,
cefpodoxime, or cefuroxime)
PLUS
Macrolide
(azithromycin, clarithromycin, or erythromycin)*
In regions with a high rate (>25 %) of
infection with high-level macrolide-resistant
Streptococcus pneumoniae
The empirical antibiotic therapy non Inpa
-IC
Ut
tien
t
re a s
Medicare Study tme
nt

A respiratory fluoroquinolone
(moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
OR
An antipneumococcal beta-lactam
(preferred agents: cefotaxime, ceftriaxone, or ampicillin- sulbactam; or
carbapenem for selected patients)
PLUS
macrolide
(azithromycin, clarithromycin, or erythromycin)
The empirical antibiotic therapy In
ICU patie
tre nts
Medicare Study atm
ent

Antipneumococcal beta-lactam
(cefotaxime, ceftriaxone, or ampicillin-sulbactam)
PLUS
Azithromycin ! Carbapenem
OR

Antipneumococcal beta-lactam
(cefotaxime, ceftriaxone, or ampicillin-sulbactam)
PLUS
Respiratory fluoroquinolone
(moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
OR

For penicillin-allergic patients, respiratory fluoroquinolone

(moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
PLUS
Aztreonam
Antibiotic therapy duration in CAP
 Non-complicated standard CAP duration 5-7 days
 There is no RCT indicating the optimum duration
 Variable - agent and antibiotic function
 Legionella, Pseudomonas, Gram negative aerobics 
21 days
 Patients treated ambulatory with azithromycin 
5 days
Antibiotic therapy in CAP
 Switching from intravenous to oral administration:
white blood cells count return to normal
min 2 measurements t < 37.5 ºC at interval > 16 hours
improving cough and dyspnea

 Antibiotics with good intestinal absorption

 Amoxicillin
 "respiratory" quinolone (moxi-, levofloxacin)
 ! i.v. - in case of low BP, nausea or vomiting
Non-complicated CAP – favourable response
 fever - decreases in 2 days
 leukocytosis - decreases in 4 days
 physical signs persist ↑
 radiological abnormalities  can persist until 4-12 weeks
Discharge criteria in CAP
 Oral temperature < 37.5 °C min 24 hour
 Heart rate <100 / min
 Respiratory rate <24 / min
 SBP > 90 mmHg
 SO2> 90%
 The ability to hydrate and feed
 Adequate mental status
 Associated diseases – stable
 Complications resolved
 Factors to consider when the CAP evolves
unfavorable

 Is there a mechanical cause that prevents

improvement? (bronchial obstruction - carcinomas,
plugs)

 Are there an underestimated piogenic metastasis?

(empyema, cerebral abscess, endocarditis, spleen
abscess, osteomyelitis)

 Does the patient have antibiotic-induced fever?

 Patient with CAP

1. Appreciates the severity of pneumonia - vital signs, RF/min, SO2

2. Ensures proper oxygenation and circulatory support
3. Identifies the etiological agent
4. Determine whether treatment will be done at home or in hospital
(internal medicine/pneumology dpt or intensive care unit)
5. Initiates empirically antibiotic treatment
6. Excludes empyema
7. Never forget the possibility of etiology with KB or Pneumocystis
8. Consider pulmonary embolism in patients with pleural chest pain
 Patient with CAP
1. Monitor and treat comorbidities
2. Monitor the patient until the vital signs are stabilized
3. Appreciates the ability to carry out daily activities
4. Appreciates mental status
5. Provides prevention tips: smoking cessation, influenza and anti-
pneumococcus vaccination, prevention of aspiration of orotracheal
secretions
6. Follow-up radiological resolution - documented in patients
> 40 years and smokers
PULMONARY COMPLICATIONS OF CAP
Pleural effusion & Empyema
 40% hospitalized patients with CAP  pleural effusion
 Mandatory – X-ray in lateral decubitus on affected side 
thoracentesis if D > 1 cm
 Empyema - if:
 - pH <7.0
 - glucose  DRAINAGE !!!
 - LDH > 1000 U
 - germs on smear or in cultures

Aspiration of franc pus 

drain tube, intrapleural lithic agents, sometimes thoracotomy - under
thoracic surgeon supervision
 Pulmonary abscess
Area of suppuration 
destruction of the parenchyma 
radiological aspect of the air-liquid cavity

Risk factors:
impaired cough reflex, aspiration, alcoholism, anesthesia, drug
abuse, epilepsy, stroke; dental caries, bronchiectasis, bronchial
carcinoma, pulmonary infarction

Frequently with aerobic and anaerobic bacteria!!!

Pulmonary abscess
 Requires targeted antibiotic therapy depending on the isolated germ
 Duration - 6 to 8 weeks till X-ray resolution
 Failed to ~ 10% cases  percutaneous drainage or lobectomy
 Not every pulmonary cavity = abscess

Neoplasia Wegener granulomatosis

Rheumatoid nodules Pulmonary infarction
TB lesions Fungi infections
Recurrent pneumonia
 10-15% hospitalized patients  new episode in the next 2
years
! if the same anatomical segment is affected 
? bronchial obstruction through the tumor, foreign body ?
 Common causes:
 repeated macrospiration, bronchiectasis, COPD
 frequent pneumonia with different locations without risk factors for
aspiration  immunosuppression? (! HIV)