Respiratory JC014: Fever And Purulent Sputum: Influenza, Pneumonia: Common Organisms And Anti-microbial Agents For Pneumonia

Question 1

***Lower respiratory tract infections

Answer 1

1. Acute bronchitis
2. Acute exacerbation of Chronic bronchitis
3. Bronchiectasis
4. Pneumonia
5. Lung abscess

Question 2

Case:
- 35 male
- chronic smoker
- good past health
- high fever 3 days
- URTI symptoms (sore throat, running nose)
- increasing cough + greenish sputum
- progressive SOB
- right side pleuritic chest pain
- high swinging fever with chills + rigors
- oral antibiotics + paracetamol but worsening

Answer 2

P/E:
- respiratory distress
- alert
- dullness
- **bronchial breath sound
- **coarse inspiratory crackles over right lower chest
- BP 90/50 (borderline low)
- SpO2 92% on room air (RA) (low)

CXR:
- Right lower lobe consolidation

Clinical diagnosis:
- Community-acquired pneumonia

Question 3

Pneumonia

Answer 3

Definition:
- Inflammation of Lung ***parenchyma ∵ infective agents (Bacteria, Virus, Fungi)
- vs Pneumonitis (non-infectious cause of inflammation)

Classifications:
1. Anatomical (can be due to different agents)
- **Lobar
- Multi-lobar
- **Bronchopneumonia

2. Etiological
   - Bacterial
   - Viral
   - Fungal (rare)
3. Clinical
   - CAP
   - HAP
   - VAP (ventilator)
   - Aspiration

Question 4

Epidemiology of Pneumonia

Answer 4

• 2nd leading cause of death since 2012

Question 5

Causative pathogens of Pneumonia

Answer 5

Depends on:
- Clinical settings
- Host factors

1. Bacteria
2. Viruses
3. Fungi
4. Mycobacterium TB

Question 6

***Causative Bacteria in Pneumonia

Answer 6

Gram +ve (***記: SHS):
- Streptococcus pneumoniae (CAP ++, HAP +) (Pneumococcus)
- Haemophilus influenzae (CAP +, HAP +)
- MRSA (HAP ++)

Gram -ve (***記: PK):
- Klebsiella pneumoniae, Pseudomonas aeruginosa (HAP ++)

Atypical (***記: MCL):
- Mycoplasma pneumoniae (CAP +, Aspiration +)
- Legionella pneumophila (CAP +, Aspiration +)
- Chlamydophila pneumoniae (CAP +, Aspiration +)

Anaerobes:
- Bacteroides spp. (GI / Oral flora) (Aspiration ++)

(Bronchiectasis:
- Haemophilus influenzae
- Pseudomonas aeruginosa

COPD exacerbation:
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis)

Question 7

Community-acquired pneumonia (CAP)

Answer 7

Symptoms:
- Cough, Sputum, Haemoptysis, **Dyspnea, **Pleuritic chest pain (indicate Pleural involvement / inflammation)
- Fever, Chills, Rigor
- Confusion, Constitutional / systemic symptoms

Signs:
- Chest: **Dullness, **Bronchial breath sound, **Coarse crackles, **↑ Vocal resonance
- Vital (assess severity): BP, SpO2, mental state

History:
- TOCC

Atypical pneumonia:
- M. pneumoniae, C. pneumoniae, L. pneumophila
- Syndrome of **pneumonitis, fever
- **Normal WBC (esp. Neutrophil)
- Without identifiable bacterial pathogens from respiratory samples
- Prominent systemic complaints

Question 8

Clinical approach to CAP

Answer 8

1. Establish diagnosis
2. Identify causative pathogens
3. Assess clinical severity
4. Empirical anti-infective / antibiotic treatment

Question 9

***1. Diagnosis of CAP

Answer 9

1. Clinical diagnosis
   - Compatible respiratory S/S
2. Radiographic evidence
   - **Consolidations in Lobar pneumonia
   - **Patchy infiltrates in Bronchopneumonia
3. Further investigations:
   - **CBC (total WBC, D/C) —> identify likely organisms
   - **Electrolytes —> HypoNa in SIADH
   - LFT, RFT —> adjust antibiotic dose
   - ***ABG —> assess gas exchange
4. Identify causative organism (Retrospective)
   - **Sputum + Blood cultures
   - **Nasopharyngeal aspirate (if suspect influenza / atypical pneumonia) —> Viral studies, RT-PCR
   - ***Urine Ag test (for Legionella, Pneumococcus) (SpC Medicine: Specific, Sensitive, Rapid (hours), Cheap, +ve from day 3 - several weeks, Not affected by antibiotics)
   - Atypical pneumonia serology —> retrospective diagnosis for atypical pneumonia

Question 10

2. Initial management of CAP

Answer 10

Identifying causative agents
- Microbiological diagnosis: ***Retrospective
- still important to know about Antibiotic resistance (help refinement of antibiotic choice)

Initial management is based on Clinical setting + Hosts factors
- Co-morbidities
- Immunocompromised?
- Previous antibiotic use (prone to develop antibiotic resistance)
- Need to cover Streptococcus pneumoniae in **ALL cases of CAP
- Need to cover Legionella pneumophila in **SEVERE cases of CAP

Question 11

3. Assess clinical severity of CAP

Answer 11

Help to decide an appropriate clinical setting for management
- Outpatient
- General medical ward
- ICU

Poor prognostic factors:
- Old age
- Hypoxaemia (PaO2 <8 kPa i.e. already respiratory failure)
- High (>11) / Low (<4) total WBC
- High urea (>8)
- Multilobar involvement
- Bacteraemia (positive blood culture)

***CURB-65 (>2 factors present —> hospital admission)
- Confusion
- Urea >7
- RR >30
- BP low (SBP <90 / DBP <60)
- >65 yo

Question 12

Empirical antibiotics for CAP

Answer 12

• Appropriate antibiotics
• Timely (within 6-8 hours)

Choice depends on Clinical settings + Risk factors for multi-resistant pathogens
- Need to cover Streptococcus pneumoniae in **ALL cases of CAP
- Need to cover Legionella pneumophila in **SEVERE cases of CAP (Macrolide (SpC Medicine))

Treatment:
Penicillin with β-lactamase inhibitor (+/- Macrolide / Tetracycline)
- **Augmentin +/- **Clarithromycin / Azithromycin / Doxycycline
- 7-10 days

Risk factors for multi-resistant pathogens:
- Recent / Frequent antibiotic use
- Recent / Frequent hospitalisation
- Nursing home residents
- Immunosuppressive disease / therapy

Question 13

General supportive therapy for Pneumonia

Answer 13

1. ***O2 / Mechanical ventilation for respiratory failure
2. Chest physiotherapy
3. ***Fluid rehydration (prevent high urea)
4. Treat underlying COPD with bronchodilators
5. ***Control cardiac arrhythmia (e.g. AF)

Question 14

Hospital-acquired pneumonia (HAP)

Answer 14

Pneumonia **>48 hours after hospitalisation
- related to aspiration of **oropharyngeal secretions colonised by hospital-acquired organisms
- more resistant bacteria (MRSA) + Gram -ve bacilli (記: ***PK: P. aeruginosa, K. pneumoniae)

Predisposing factors:
- General debility
- Old age
- Smoking
- COPD
- **Aspiration
- **Post-general anaesthesia (GA)
- H2 blockers / Antacids
- **NG tube
- **Mechanical ventilation (Ventilator-associated pneumonia (VAP))

Question 15

Empirical antibiotics for HAP

Answer 15

Cover:
1. Streptococcus pneumoniae
2. Resistant Gram +ve (may include MRSA if appropriate)
3. Gram -ve (P. aeruginosa, ***K. pneumoniae, Extended spectrum β-lactamase (ESBL) producing organisms)
4. Anaerobes (∵ aspiration)

Treatment:
Extended spectrum Penicillin / 3rd gen Cephalosporin / Carbapenem
- **Piperacillin-Tazobactam
- **Meropenem

Question 16

Aspiration pneumonia (+ SpC Medicine)

Answer 16

Predisposing factors:
- **Altered consciousness (e.g. Syncope / CVA, Epilepsy)
- **Alcoholism
- Vomiting
- Dysphagia, Esophageal diseases (e.g. Ca esophagus, esophageal stricture)
- **Neurological disorders (Bulbar palsy, Bulbar: Brainstem - Midbrain + Cerebellum, MG, Dermatomyositis, Scleroderma, Motor neuron disease)
- **NG tube
- Severe dental / URTI
- Terminal illness
- Drowning
(- Musculoskeletal problem e.g. Scoliosis
- Tracheo-esophageal fistula)

Causative agents:
- ***Anaerobes (oral flora)

Clinical features:
Usually affecting **dependent parts of lungs
- **Lower lobes (esp. **Right: vertical, short, wide)
- Posterior segments of upper lobes (in those mostly supine)
- Component of **chemical pneumonitis as well —> delayed CXR resolution, prone to lung abscess

Investigations:
- ***Videofluoroscopic swallowing study (VFSS)
—> assess integrity of swallowing

Question 17

Management of Aspiration pneumonia

Answer 17

1. Antibiotics
   - cover Oropharyngeal flora esp. **Anaerobes (e.g. Metronidazole)
   - **Penicillins (e.g. Augmentin)
2. Treat underlying conditions
3. Prevention of further aspiration
   - non-oral feeding (e.g. via Percutaneous endoscopic gastrostomy (***PEG tube) in bulbar dysfunction patients)

Question 18

***Complications of Pneumonia

Answer 18

1. ***Respiratory failure
   - O2 therapy
   - Ventilatory support
2. ***Septicaemia with Multi-organ failure (Septic shock)
3. **Lung abscess
   - Air-fluid level, Cavity on CXR
   - could be **polymicrobial
   - need prolonged antibiotics (4-6 weeks)
   - no need percutaneous drainage in most cases (∵ drain naturally via airway)
4. ***Parapneumonic effusion
   - ∵ pleural inflammation without infection of pleural cavity
5. Empyema thoracis
   - infection of pleural cavity (pathogen invaded into pleura)
   - pus in pleural cavity
   —> gross appearance of pleural fluid
   —> Gram’s stain
   —> culture
   - need prolonged antibiotics (4-6 weeks)
   - ***Pleural drainage needed (e.g. Intercostal tube) (∵ no natural drainage)
6. SIADH
   - HypoNa
7. Acute MI
8. ***Cardiac arrhythmia (AF)

Question 19

Recurrent pneumonia

Answer 19

Causes:
1. **Diffuse bronchopulmonary diseases (e.g. Bronchiectasis: destroyed airway, chronic colonisation of airways)
2. **Recurrent aspiration
3. ***Immunocompromised (e.g. HIV, malignancy)
4. Bronchial obstruction (∵ retained secretions e.g. by tumour, foreign body)

Investigations:
1. **CT thorax
2. **Bronchoscopy (visualise airway + obtain samples) —> e.g. for TB
3. Sputum —> AFB + Cytology (malignancy)
4. Blood —> look for immunodeficiency

Question 20

Influenza

Answer 20

Influenza virus:
- Influenza A + B
- Immunogenic surface Ag
—> Haemagglutinin (H)
—> Neuraminidase (N)

Antigenic shift: ***Major changes in Ag (e.g. H3N2 —> H1N1)
- highly pathogenic
- human do not have specific natural immunity
- worldwide pandemics

Antigenic drift: ***Minor changes in Ag
- occur continuously yearly

Question 21

Seasonal influenza

Answer 21

2 peaks
- Jan —> Mar
- Jul —> Aug

Question 22

Clinical features of Influenza

Answer 22

1. **URT symptoms
   - **running nose
   - ***sore throat
   - cough + sputum
2. Fever, Myalgia, Arthralgia
3. LRT / Systemic involvement (occasional)

Question 23

Diagnosis of Influenza

Answer 23

1. Rapid Ag test on nasopharyngeal aspirate (NPA) / swab
   - distinguish A / B
2. ***RT-PCR
   - information of virus strain
3. Viral cultures
4. Serology
   - retrospective epidemiological diagnosis

Question 24

Management of Influenza

Answer 24

1. Personal hygiene
2. Symptomatic treatment (∵ self-limiting)
3. Specific antivirals
   - Amantadine / Rimantadine
   - Neuraminidase inhibitors

Question 25

Amantadine / Rimantadine

Answer 25

• Interfere with viral ***uncoating inside cells
• Effective ONLY against ***influenza A
• Not useful in treating Avian flu
• Severe toxic effects (mainly neurological)
• Rapid emergence of drug ***resistance

Question 26

Neuraminidase inhibitors

Answer 26

Interfere with release of progeny influenza virus from infected host cells
—> Stop spread of infection in respiratory tract
- Effective against influenza **A+B
- Active when give asap (within **48 hours)
- Oseltamivir (Tamiflu: Oral), Zanamivir (Relenza: Inhaled)

Question 27

***Bronchiectasis

Answer 27

• Pathological dilatation of bronchi
• Chronic destruction of bronchi (***colonised by bacteria)
• Generalised / Localised

Causes:
1. **Mostly idiopathic (need to look out for secondary causes before concluding idiopathic)
2. Secondary causes
- **Post-infection
- **Post-TB
- **Immunodeficiency
- ***Autoimmune (e.g. RA)
- Aspiration
- Primary ciliary dyskinesia
- Cystic fibrosis

Symptoms:
1. **Chronic sputum production + cough
2. Episodes of infective **exacerbations (∵ retention of secretions in mucosal surface since cannot be cleared —> overgrowth of bacteria)
3. ***Haemoptysis: usually infective
4. Dyspnea, Chest pain, Weight loss, Fatigue

Signs:
1. Cachexic
2. **Clubbing
3. **Coarse crackles, **↓ Breath sound, **Dull
4. Associated COPD
5. **Respiratory failure
6. Progressive lung damage
7. **Lung abscesses
8. ***Empyema
9. Brain abscess
10. Other complications

Question 28

***Investigations of Bronchiectasis

Answer 28

1. CXR
   - may be normal / **tramline shadows (bronchi do not taper, parallel), **signet ring sign (prominently dilated airway compared to its accompanying pulmonary vessels)
2. ***HRCT thorax (Gold standard)
3. ***Immunoglobulins
   - look for secondary cause (e.g. deficiency can cause repeated infections)
4. ***Auto-Ab
   - look for secondary cause (e.g. RA)
5. Sputum culture, ***AFB
6. Barium studies / 24 hour esophageal pH monitoring
   - repeated reflux / aspiration
7. Ciliary / Sperm analysis
   - ***Primary ciliary dyskinesia (congenital: impaired ciliary function)
8. Neutrophil functions (rare)
9. Sweat test (measure amount of Cl in sweat: very high Cl —> cystic fibrosis)
   - ***Cystic fibrosis

Question 29

***Treatment of Bronchiectasis

Answer 29

Acute exacerbations:
- Haemophilus influenzae
- Staphylococcus aureus
- ***Pseudomonas aeruginosa (if long-standing) (poor prognosis)

1. Anti-pseudomonal antiobiotics
   - **Extended spectrum penicillins (e.g. **Piperacillin-Tazobactam)
   - **3rd gen Cephalosporin (e.g. **Ceftazidime)
   - **Carbapenems (e.g. **Meropenem)
   - Aminoglycoside (e.g. Amikacin) (Inhaled form: if colonisation by Pseudomonas + frequent exacerbation, SE: Bronchospasm, Ototoxicity, Vestibular toxicity, Nephrotoxicity (SpC Medicine))
   - Fluoroquinolone (e.g. Levofloxacin) —> Only Orally available (others IV)
2. ***ICS +/- LABA
   - in overlapped airflow obstructive disease
   (- not routine use in bronchiectasis only (SpC Medicine) (支氣管擴張不用再擴張氣管))
3. Long-term macrolides
   - **Immunomodulating rather than antibiotic effect
   - Azithromycin, Erythromycin
   - watch out for **prolonged QTc, ***sensorineural hearing impairment
   (- for recurrent exacerbation (SpC Medicine))
4. ***Postural drainage
   - use gravity to drain retained mucus
5. Chest physiotherapy
6. Surgery
   - for localised bronchiectasis
   - very limited disease
7. Lung transplantation

(SpC Medicine)
8. ***Vaccination
- Streptococcus pneumoniae
- Influenza

9. Pulmonary rehabilitation

Question 30

Severity grading system for Bronchiectasis (SpC Medicine)

Answer 30

1. ***Bronchiectasis severity index
   Parameters
   - Age
   - BMI
   - %FEV1 Predicted
   - Previous hospital admission (Has the patient been hospitalised with a severe exacerbation in the past 2 years?)
   - Number of exacerbations in previous year
   - MMRC Breathlessness Score
   - Pseudomonas colonisation (chronic colonisation is defined by the isolation of Pseudomonas aeriginosa in sputum culture on >=2 occasions, >=3 months apart in a 1 year period)
   - Colonisation with other organisms (chronic colonisation is defined by the isolation of potentially pathogenic bacteria in sputum culture on 2 or more occasions, at least 3 months apart in a 1 year period)
   - Radiological severity

Score:
- 0-4 points: Mild bronchiectasis
- 5-8 points: Moderate bronchiectasis
- >=9 points: Severe bronchiectasis

2. ***FACED score
   - F: FEV1 (>=50% = 0 points, <50% = 2 points)
   - A: Age (<70 years = 0 points, >=70 years = 2 points)
   - C: Chronic colonisation (no Pseudomonas = 0 points, presence of Pseudomonas = 1 point)
   - E: Extension (1-2 lobes affected = 0 points, >2 lobes affected= 1 point)
   - D: Dyspnea (modified Medical Research Council scale (mMRC)) (0-2 = 0 points, 3-4 = 1 point)

Score:
- 0-2 points: Mild bronchiectasis
- 3-4 points: Moderate bronchiectasis
- 5-7 points: Severe bronchiectasis

Question 31

Silouette sign on CXR (SpC Medicine)

Answer 31

When 2 structures of similar density are side by side, their borders become undefinable on a plain XR
- When a lung lobe is collapsed / consolidated
—> density is similar to heart
—> if on RML / LUL (where the heart situated in between)
—> cannot see border of consolidation
vs
—> if on RLL / LLL (behind the heart)
—> can see border of consolidation clearly

Philip Li:
- Cannot see heart border: Middle lobe
- Cannot see diaphragm: Upper lobe

Question 32

Lung abscess (SpC Medicine)

Answer 32

Suppurative lung lesion with cavity on CXR

Cavitating organism causing lung abscess:
1. TB
2. Klebsiella
3. Staphylococci aureus

Solitary lung abscess:
1. **Inadequately treated pneumonia (esp. Staphylococcus aureus, Klebsiella)
2. **Bronchiectasis-associated
3. Aspiration
4. FB / Tumour obstruction
5. Amoebic, from liver amoebic abscess (in RLL)

Multiple lung abscesses:
1. **Septicaemia (via RV + RA)
2. **IV catheter (esp. prolonged use for chemotherapy (Hickmann’s catheter) / vascular access for HD)
3. ***IV drug abuse (severe phlebitis)
4. R-sided endocarditis (echo)

P/E:
1. Vital signs
2. Respiratory exam
3. Heart complications
- Severe phlebitis and evidence of IV drug abuse
- Splinter haemorrhage
- Murmurs
4. Brain abscess
- Conscious level
- Focal motor signs
- Fundi: haemorrhage / papilloedema (increased ICP)
5. Urinalysis: RBC suggestive of microscopic haematuria

Investigations:
1. CXR: Suppurative lung lesion with cavity
2. CBP + D/C
3. LRFT
4. Blood culture
5. Sputum for Gram stain, C/S
6. Sputum for ova and parasite
- whenever a parasitic cause for lung abscess is suspected
7. FOB
8. Echocardiogram (despite no murmur, vegetation may still be present in heart)
9. Full septic workup: HBV, HCV, HIV, MRI brain as indicated

Treatment:
1. High-dose IV empirical antibiotics
- Depending on scenarios and cultures, e.g. aspiration, bronchiectatic / parasitic abscess
- Prolonged duration (4-6 weeks)
- No need of percutaneous drainage in most cases (because natural drainage through airway)

Question 33

IV drug abuse-associated disease

Answer 33

1. Addiction
2. Direct abuse drug toxicity (e.g. morphine overdose)
3. Phlebitis + thrombosis
4. Multiple lung abscesses
5. Other organ abscesses
   - Brain abscess —> MRI brain
   - Liver abscess (pathogens not completely filtered off in lung but carried to systemic circulation)
6. R-sided infective endocarditis (S. auerus)
7. HBV / HCV infections
8. HIV infections
9. Tetanus

Question 34

Pneumocystis pneumonia (PCP)

Answer 34

• Pneumocystis jirovecii (previously P. carinii)
• AIDS-defining illness
  —> Lymphopenia
  —> **Reversed CD4:CD8 ratio (normal 1-4 (web))
  —> **CD4 <200 very likely cause opportunistic infections

CXR:
- ***Bilateral Diffuse ground glass opacity (Pathognomonic) (DDx: Viral infection e.g. CMV (SpC Revision))
- Lymphopenia

Diagnosis:
- **Induced sputum / BAL fluid: cysts of P. jirovecii in lung tissue, stained with **Silver stain
- ***NPA for PCR
- Cannot be cultured
- Lung biopsy not done since too invasive

Treatment:
1. **21 days **Co-trimoxazole (Septrin)
- PO/IV (= IV Pentamidine)
- CI in G6PD: must check status

2. ***Adjunctive steroid for severe PCP with PaO2 <9kP
   - Cytokine storm may happen after killing of microbes with cotrimoxazole —> give adjunctive steroid to damp down severe cytokine storm / inflammatory response

Prophylaxis:
1. Primary: CD4 <200
2. Secondary: with history of PCP
- Co-trimoxazole in prophylactic dose (unless HAART renders CD4 >200 >3m)

Question 35

Primary Ciliary Dyskinesia (KWH Paed Teaching)

Answer 35

Inheritance:
- Autosomal recessive mainly

Clinical features:
1. Pulmonary
- Chronic productive cough
- Recurrent pneumonia
- Recurrent rhinosinusitis

2. Eustachian tube
   - Otitis media
3. CNS
   - Headache, fatigue
4. Fertility
   - Immotile sperm
   - Ectopic pregnancy

Associated symptoms:
- Situs inversus
- Kartagener syndrome: Triad of Situs inversus, Chronic sinusitis, Bronchiectasis
- Transposition of great vessels, other cardiac abnormalities
- Pyloric stenosis
- Epispadias

Diagnosis:
- **PICADAR score (Prerequisite question: Does patient have daily wet cough that started in early childhood?)
- **Ciliary brush
- ***Nasal NO (Very low / absent)

Management:
1. **Antibiotic for infections
2. Airway clearance therapy
- **Oscillating PEP device, Chest physiotherapy
- ***Nasal washing
- Hypertonic saline
3. Vitamin D (for chronic lung disease)
4. Vaccination

Question 36

DDx of Micronodular shadowing on CXR (SpC Revision)

Answer 36

1. Lymphangitis carcinomatosis
2. Miliary TB
3. Silicosis
4. Sarcoidosis
5. Pulmonary haemosiderosis

Question 37

DDx of Diffuse ground glass appearance on CXR (SpC Revision)

Answer 37

Ground glass:
- Increased attenuation of the lung with preserved bronchial and vascular markings (web)

For patients on immunosuppressants:
1. Pneumocystis jirovecii pneumonia
2. Viral infection (e.g. CMV)

Self notes:
1. Atypical pneumonia (e.g. Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila)
2. Interstitial lung disease (Pulmonary fibrosis)
3. Pulmonary edema

Question 38

Diagnosis of TB and PCP (SpC PP)

Answer 38

TB:
1. ZN stain
2. AFB smear
3. PCR
4. Culture

PCP:
1. Silver stain
2. Cysts of PCP
3. PCR