Pneumonia

DR MNMN
28th November 2019
 Pneumonia
 Acute inflammation of lung caused by
microorganism
 Leading cause of death until 1936
 Discovery of sulfa drugs and
penicillin
 Still leading cause of death from
infectious disease
Risk factors

1. Viral infections (damage cilia and produce serous

exudates)
2. Age (elderly‐ defect in swallowing, ↓ immunity)
3. Alcoholism (depress coughing and epiglottis function)
4. Smoking (damage epithelial cells and impair cilia
functions)
5. Asthma/COPD
6. Immunosuppression (AIDS, transplant pt, cancer chemo)
Risk factors
7. Dementia
8. Diabetes Mellitus‐ defective neutrophil function,↓ CMI
9. Renal Failure‐ ↓ humoral response, ↓ leukocyte
chemotaxis, complement depletion
10. Chronic lung diseases
11. Cold Weather (dry mucous membrane and person to
person spread)‐ common in winter
12. Heart Disease‐ Impaired lymphatics & alv macrophage
function, oedema promotes bacterial growth
Organisms implicated
Classification of Pneumonia
Types of Pneumonia
 Community-Acquired (CAP)
 Health-Care Associated Pneumonia (HCAP)
 Hospitalization for > 2 days in the last 90 days
 Residence in nursing home or long-term care facility
 Home Infusion Therapy
 Long-term dialysis within 30 days
 Home Wound Care
 Exposure to family members infected with MDR bacteria
 Hospital-Acquired Pneumonia (HAP)
 Pneumonia that develops after 5 days of hospitalization
Includes:
 Ventilator-Associated Pneumonia (VAP)
 ICU Pneumonia (ICUAP)
CAP pathogen source
 Inhalation
 Aspiration
 Hematogenous

 Primary inhalation: when organisms bypass normal

respiratory defence mechanisms or when the Pt inhales
aerobic GN organisms that colonize the upper
respiratory tract or respiratory support equipment
 Aspiration: occurs when the Pt aspirates colonized
upper respiratory tract secretions
 Hematogenous: originate from a distant source and
reach the lungs via the blood stream.
Various defence mechanisms
that protects lung from
infection
 Anatomic barriers –epiglottis, larynx
 Cough reflexes
 Tracheobronchial secretions
 Mucocilliary lining
 Cell & humoral mediated immunity
 Dual phagocytic system-alveolar macrophages &
neutrophils
Pathogenesis cont.

 Invasion occurs as a result of

 Defect in host defence mechanism
 Overwhelming inocculum
 Lung infection with viruses suppress the
antibacterial activity of the lung by impairing
alveolar macrophage function & mucocilliary
clearance thus setting the stage for secondary
bacterial pneumonia
Pathophysiology

4 stages of pneumonia
 Consolidation
 Red hepatisation
 Grey hepatisation
 Resolution
Pathophysiology:
Pneumococcal Pneumonia
 Consolidation=replacement of air
with transudate/pus/blood/cell
ect.
 Congestion from outpouring of fluid
into alveoli
 Microorganisms multiply and
spread infection, interfering with
lung function
Pathophysiology:
Pneumococcal Pneumonia
 Red hepatization
 Massive dilation of capillaries
 Alveoli fill with organisms,
neutrophils, RBCs, and fibrin
Causes lungs to appear red and
granular, similar to liver
Pathophysiology:
Pneumococcal Pneumonia

 Gray hepatization
Blood flow decreases
Leukocyte and fibrin
consolidate in affected part
of lung
Pathophysiology:
Pneumococcal Pneumonia

 Resolution
Resolution and healing if no
complications
Exudate lysed and processed
by macrophages
Tissue restored
Pathophysiologic course of
pneumococcal pneumonia
Diagnosis: Just FYI
Typical pneumonia:
Clinical presentation
 • Usual bacteria
 – Sudden/subacute onset
 – Fever with chills, rigors
 – Productive cough, Mucopurulent sputum
 – Tachypnea and tachycardia
 – breathlessness
 – Pleuritic chest pain
 – Breath sound: crackles and rales
 – CXR: air‐bronchogram, consolidation
Atypical pneumonia:
Clinical presentation
 Atypical
– Gradual onset
– Afebrile
– Dry cough
– Uni/bilateral patchy, infiltrates (CXR)
– WBC: usual normal or slight high
– Sore throat, myalgia, fatigue, diarrhea
– Common etiology
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
• Legionella pneumophilla
• Mycobactria
• Virus, Others
 Complications

 Pleurisy
 Pleural effusion
 Usually is sterile and reabsorbed
in 1-2 weeks or requires
thoracentesis
 Atelectasis
 Usuallyclears with cough and
deep breathing
 Complications

 Delayed resolution
 Persistent infection seen on x-ray as
residual consolidation
 Lung abscess (pus-containing
lesions)
 Empyema (purulent exudate in
pleural cavity)
 Requires antibiotics and drainage of
exudate
 Complications

 Pericarditis
 From spread of microorganism
 Arthritis
 Systemic spread of organism
 Exudate can be aspirated
 Meningitis
 Patientwho is disoriented,
confused, or somnolent should have
lumbar puncture to evaluate
meningitis
 Complications

 Endocarditis
 Microorganismsattack
endocardium and heart valves
 Manifestations similar to
bacterial endocarditis
 Collaborative Care

 Antibiotic therapy
 Oxygen for hypoxemia
 Analgesics for chest pain
 Antipyretics
 Influenza drugs
 Influenza vaccine
 Fluid intake at least 3 L per day
 Caloric intake at least 1500 per day
Our syllabus covers:

 Antibiotics for pneumonia

 Mucolytic
 Pulmonary surfactants ?
 Respiratory stimulants ?
 Antibiotics for pneumonia

Antibiotics is actually covered in PHD224.

Hence for now, it is sufficient to know their class and an example for each
MOA/SE/ADR- covered next semester. Instead, lets look into pneumonia
management using antibiotics
 Bacterial causes
 Streptococcus pneumoniae (20% to 60% of CAP cases)
 Haemophilus influenzae (3% to 10% of CAP cases)
 L. pneumophila (1% to 5% of adult pneumonias) (2% to 8% of
CAP cases)
 Klebsiella, Pseudomonas, Escherichia coli, Staphylococcus
aureus (3% to 5% of CAP cases)
 Atypical organisms such as M. pneumoniae, C. pneumoniae,
and L. pneumophila implicated in up to 40% of cases of CAP.
 Influenza infection is one of the important predisposing
factors to S.pneumoniae and S. aureus pneumonia
 Gram‐negative organisms cause 80% of nosocomial
pneumonias
Pneumonia management
options for CAP
• Outpatient
• Inpatient
• ICU management
Bacterial causes for CAP
Factors for consideration

• Risk of death from the pneumonia,

• Disease severity
• Presence of comorbid conditions,
• Need for advanced diagnostics,
• Inability to take oral medications
• Lack of social support
Criteria for risk
stratification (CURB‐65)
• Confusion
• Urea ≥20mg/dL
• Respiratory rate ≥30/min
• Low blood pressure (diastolic blood
pressure ≤60 mm Hg or systolic blood
pressure ≤90 mm Hg)
• Age ≥65 years
Scoring System

 To determine Risk of Complications in

Patients with Community‐Acquired
Pneumonia
 score < 50: Outpatient treatment
 scores > 90: hospitalization
 Proper management of patients with
scores of 70–90 requires careful
application of clinical judgment.
Criteria for ICU admission
Criteria for clinical stability
• Temperature ≤37.8° C
• Heart rate ≤100 beats/minute
• Systolic blood pressure ≥90 mm Hg
• Respiratory rate ≤24 breaths/minute
• Oxyhemoglobin saturation ≥90% or PO2 ≥60 mm Hg
on preadmission level of oxygen supplementation
4 out of 5 criteria need to be fulfilled in stability
criteria
 Generally 7‐10 days of antibiotics are sufficient
 Once the stability criteria are met, patient can be
switched to oral antibiotics (same group)
Pneumonia management
options for HAP
 Divided into ICU HAP or non‐ICU HAP
depending upon whether this infection is
acquired in the intensive care unit (ICU)
or in other clinical areas (e.g. wards)
 “Nosocomial” Pneumonia (slide 8)
 HAP
 HCAP
 VAP
 ICUAP
 Pneumonia management
options for HAP
• HAP is the second most common nosocomial
infection
• HAP accounts for up to 25% of all ICU infections and
more than 50% of the entire antibiotic prescriptions.
• The crude mortality rate for HAP
may be as high as 30–70%
• The risk of HAP/VAP is the highest
early in the course of hospital stay
Pneumonia managem
options for HAP
• Start antibiotics as early as possible
• The exact choice of antibiotic to be started is based
on local availability, antibiotic resistance patterns,
preferred routes of delivery, other complicating
factors, and cost.
• The initial combination therapy should be
converted to appropriate monotherapy once culture
reports are available
• The strategy for de‐escalation of antibiotics is
strongly recommended
Antibiotics used in HAP/VAP
 Things to consider in
HAP/VAP management
• Among patients with suspected VAP in whom an alternate
cause for pulmonary infiltrates is identified, it is
recommended that antibiotics should be stopped
• If cultures are sent after initiation of antibiotics and
there is clinical improvement with subsequent cultures
being sterile, antibiotics should be continued for 7 days
followed by assessment.
• Empiric antifungal therapy (on day 3) should not be used
as a routine in all patients if cultures are sterile and there
is clinical worsening
 Things to consider in
HAP/VAP management
 In patients with VAP due to Pseudomonas,
Acinetobacter, and MRSA, a longer
duration (14 days) of antibiotic course is
recommended.
 Assessment of CPIS on day 7 may identify
the patients in whom therapy could be
stopped early.
 In other patients with VAP who are
clinically improving, a 7‐day course of
antibiotics is recommended.
Preventive strategies for
VAP
Mucolytic for pneumonia
 Drug Class: Mucolytic Agents
Drug: acetylcysteine (Mucomyst)
 Actions: Dissolve chemical bonds in mucus
 Uses: Dissolve abnormally viscous mucus
 Treat chronic emphysema, emphysema with bronchitis,
asthmatic bronchitis, pneumonia
 Common adverse effects: Nausea, vomiting
 Serious adverse effects: Bronchospasm
 Can also be used to treat Tylenol toxicity.
 Concurrent use of a bronchodilator may be necessary to
prevent bronchospasm.
 Therapeutic outcome: improved airway flow.
Pulmonary surfactant
 Pulmonary surfactant is a mixture of lipids and proteins
which is secreted by the epithelial type II cells into the
alveolar space.
 Its main function is to reduce the surface tension at the
air/liquid interface in the lung.
 Pulmonary surfactant acts as a carpet of lipids and specific
proteins coating the interior of the lung, thus preventing
end-expiratory collapse of the alveoli and small airways
 In pneumonia, bacteria induce changes in pulmonary
surfactant->pulmonary surfactant became inactivated
Pulmonary surfactant
 The bacteria mediated occur directly on secreted
surfactant or indirectly through pulmonary type II
epithelial cells.
 The bacterial component most likely responsible is
endotoxin since gram-negative bacteria more often
induce these changes than gram-positive bacteria.
 Also, endotoxin and gram-negative bacteria induce
similar changes in surfactant..
 The interaction of bacteria or endotoxin with secreted
surfactant results in changes in the physical (i.e. density
and surface tension) properties of surfactant.
Synthetic pulmonary
surfactants
 Pulmonary surfactant preparations consist of
phospholipids (mainly DPPC) combined with spreading
agents such as SP-B and SP-C.
 Synthetic pulmonary surfactants:
 Colfosceril palmitate (Exosurf) - a mixture of DPPC with
hexadecanol and tyloxapol added as spreading agents
 Pumactant (Artificial Lung Expanding Compound or ALEC) -
a mixture of DPPC and PG
 Lucinactant (KL-4) - composed of DPPC, palmitoyl-oleoyl
phosphatidylglycerol, and palmitic acid, combined with a
21 amino acid synthetic peptide (sinapultide) that mimics
the C-terminal helical domain of SP-B.
 Venticute - DPPC, PG, palmitic acid and recombinant SP-C
 Lucinactant (trade name Surfaxin) is a liquid medication
that contains DPPC, POPG as the sodium salt, and palmitic
acid.
Animal derived surfactants
 Beractant
 (Alveofact) - extracted from cow lung lavage fluid,
manufacturing by Boehringer Ingelheim
 (Survanta) - extracted from minced cow lung with
additional DPPC, palmitic acid and tripalmitin,
manufacturing by Abbvie
 (Beraksurf) - extracted from minced cow lung with
additional DPPC, palmitic acid and tripalmitin,
manufacturing by Tekzima
 Calfactant (Infasurf) - extracted from calf lung lavage
fluid
 Poractant alfa (Curosurf) - extracted from material
derived from minced pig lung
 Beractant: Indications and
ADR
 Neonatal respiratory distress syndrome (MIMS Malaysia)
 ADR
 Significant: Transient bradycardia and oxygen
desaturation, nosocomial sepsis, endotracheal tube
obstruction.
Nervous: Seizures, intracranial haemorrhage.
CV: Hypotension, HTN, tachycardia, ventricular
tachycardia, aortic thrombosis, cardiac failure, cardio-
respiratory arrest, increased apical pulse, persistent foetal
circulation, air embolism, total anomalous pulmonary
venous return.
GI: Abdominal distention, haemorrhage, intestinal
perforations, volvulus, bowel infarct, feeding intolerance,
stress ulcer.
 ADR cont.

 Resp: Pulmonary haemorrhage, apnoea, emphysema,

hypo- and hypercapnia, subglottic stenosis, paralyzed
diaphragm, resp failure.
Hepatic: Hepatic failure.
Genitourinary: Renal failure, haematuria.
Endocrine: Adrenal haemorrhage, hyperphosphataemia.
Haematologic: Coagulopathy, thrombocytopenia,
disseminated intravascular coagulation.
Musculoskeletal: Inguinal hernia.
Others: Fever, deterioration.
MOA

 It replaces deficient or ineffective endogenous lung

surfactant in neonates w/ resp distress syndrome (RSD).
 An efficient surfactant lowers surface tension between
air and alveolar surface, hence preventing the alveoli to
collapse during expiration.
Respiratory stimulants
(Analeptics)
 Used to increase ventilation in patients in whom oxygen
therapy is followed by reduction in ventilation.
 Stimulate coughing and help patient to expel
secretions.
 Satisfactory response characterized by return of deeper
breathing & consciousness & reduction in carbon dioxide
tension in blood.
 Doxapram 1.5 – 4 mg/min IV is given as respiratory
stimulant along with assisted mechanical ventilation.
 Almiprine bismethylate, a piperaizne derivative
selectively stimulates peripheral chemoreceptors &
claimed to stimulate ventilation in hypoxia patients.
Doxapram
 Indication: Post-op resp depression and Acute resp
failure
 ADR
 Significant: Dysrrhythmias, seizure, HTN or hypotension,
dyspnoea.
Nervous: Confusion, convulsions, dizziness, hallucinations,
headache, hyperactivity.
GI: Diarrhoea, nausea, vomiting.
Resp: Bronchospasm, cough, hiccup, laryngospasm,
hyperventilation, rebound hypoventilation.
Genitourinary: Urinary retention, urinary bladder
stimulation w/ spontaneous voiding.
Musculoskeletal: Muscle fasciculation or spasticity.
Dermatologic: Flushing, sweating, warm sensation.
Others: Fever.
 Doxapram: MOA

 Doxapram stimulates respiration through action on

peripheral carotid chemoreceptors.
 It also directly stimulates the central respiratory center
in medulla w/ progressive stimulation of other parts of
the brain and spinal cord at higher doses