IC16 LRTI

Question 1

What is acute bronchitis? What is the signs and symptoms of acute bronchitis? How would you treat it? What are the criteria for returning to see the dr?

Answer 1

Acute Bronchitis
Inflammation of the trachea and lower airways
Mostly viral cause

Need differential diagnosis:

• common cold, cold variant asthma, COPD, lung cancer, acute exacerbation of bronchiectasis, acute exacerbation of chronic cough in smoker, acute rhinosinusitis

Diagnosis:

• based on clinical presentation
• NO need diagnostic test

Treatment:

• Self-limiting
• No need antibiotics UNLESS secondary bacterial infection
  o then will use antibiotics for that rather than for the acute bronchitis)

Clinical Presentations: Acute Cough for < 3wks (NOT more than 3wks)

Return or call the clinic:
1. Fever
2. Shortness of breath
3. Chest pain
4. Cough increases in extent or frequency
5. Significant cough persists beyond 3 weeks

Question 2

What are the difference between acute bronchitis and pneumonia:

Answer 2

Points Bronchitis Pneumonia
Cause of infection: Viral_Bacterial (rarely fungal or viral)
Site of infection: trachea and large bronchus_alveoli and lung parenchyma
S&S: Acute cough 3wks or less_A lot (below)
Treatment: Self-limiting. Unless worsens into bacterial infection (need antibiotics)_Antibiotics depending on the type and severity of the pneumonia

Question 3

What is pneumonia and the pathophysiology?

Answer 3

• Lower respiratory tract infection (LRTI)
• infection and thus inflammation of the alveoli and surrounding lung tissues
• infection of the lung parenchyma
• proliferation of microbial pathogens in the alveolar structure
  o Exudate into alveoli –> fluid accumulation –> cough
  o Affect gas exchange –> hypoxia –> tachypnea
  o inflammation (vasodilation) –> hypotension

Question 4

What are the source of infection of pneumonia?

Answer 4

1. Aspiration of oropharyngeal secretions
2. Inhalation of aerosolized droplets
3. Hematogenous spreading (bloodstream)

Question 5

What are the generel risk factors of pneumonia?

Answer 5

1. Smoking –> reduce neutrophil function and damage lung epithelium
2. Chronic Lung Diseases –> asthma, COPD, lung cancer –> destroy lung tissue and offer more niduses for infection
3. Immune Suppression –> HIV, corticosteroids, sepsis, chemotherapy

Question 6

What are the risk factors of CAP and how to prevent CAP?

Answer 6

1. History of Pneumonia
2. Smoking, chronic lung diseases, immune suppression

Prevention:
- Smoking cessation
- Immunization (influenza, pneumococcal)

Question 7

What are the subjective evidence of CAP?

Answer 7

Clinical Presentations of Pneumonia:
Systemic: Fever, chills, malaise, mental status change, tachycardia, hypotension

Local: Cough (dry), chest pain (from coughing), shortness of breath, tachypnea (>24bpm), hypoxia, increased sputum production

Lung auscultation (Physical Examination)
- Diminished breath sounds when inhaling
- Crackling when lung expands

Question 8

What are the objective evidences for pneumonia?

Answer 8

X-ray for everyone with suspected pneumonia

1. Need X-ray (or CT scan or MRI)
   a. New infiltrates or consolidation (white patches)
   b. Should be unilateral
2. General Lab test (WBC, CRP, Procalcitonin)
3. Urinary Antigen test (for severe CAP or hospitalized pts)
   a. test whether patient had exposure to it but doesn’t tell whether it was in the past or now since it can still be positive even after on antibiotics
4. Gram stain & Culture
   a. Sputum
   i. Less yield
   ii. Contaminated – by oropharyngeal secretions
   b. Lower respiratory culture
   i. Bronchoalveolar lavage (BAL)
   ii. Invasive
   iii. Less contaminated
   c. Blood culture (for hospitalised pts)
   i. Rule out bacteremia

Blood and respiratory gram stain and culture done in hospitals for:

1. Severe CAP (use IDSA criteria)
2. Risk factors for DRO e.g. MRSA/PA
   a. Empirically treated for MRSA/PA
   b. Infected with MRSA/PA in the last 1 year
   c. Hospitalized / Parenteral antibiotic in the last 90 days

Question 9

What are CAP, HAP, VAP?

Answer 9

Community-acquired Pneumonia:
1. Onset in community
OR
2. <48hrs after hospital admission

Hospital-acquired Pneumonia:
48hrs or more after hospital admission

Ventilator-associated Pneumonia:
48hrs or more after starting on mechanical ventilation

Question 10

What do you use to determine how to treat CAP?

Answer 10

CURB-65 and IDSA criteria for severe CAP

Question 11

What is CURB-65?

Answer 11

Determine where to treat patient

5 variables, 3 mortality risk classes
1. Confusion (new onset)
2. Urea > 7 mmol/L
3. Respiratory rate >= 30 breaths per min
4. Blood Pressure < 90/60mmmHg
5. >= 65 y/o

Classes:
0 and 1 –> Outpatient
2 –> inpatient
3 or more –> inpatient and consider ICU

Question 12

What is IDSA criteria?

Answer 12

To consider as severe CAP

1 or more major criteria:

• Mechanical ventilation
• Septic shock requiring vasoactive medications

OR

3 or more minor criteria:

• RR >= 30 bpm
• PaO2/FiO2 <= 250
• Urea > 7 mmol/L (uremia)
• Leukopenia (WBC < 4 x 10^9/L)
• Multilobar infiltrates (extensive)
• Confusion / disorientation
• Hypothermia (core temp. < 36 degrees)
• Hypotension requiring aggressive fluid resuscitation

Question 13

What is the likely pathogen(s) that cause outpatient CAP without comorbidities? What is the empiric therapy?

Answer 13

Outpatient (NO comorbidities)

Pathogen:
1. Streptococcus Pneumonia

Empiric therapy:
1. PO Amoxicillin 1g Q8h
(2nd line: PO levofloxacin / moxifloxacin)

Ciprofloxacin does not cover streptococcus p.

High dose amoxicillin to takckle penicillin resistant strep pneumonia

All 5 days

Question 14

What is the likely pathogen(s) that cause outpatient CAP with comorbidities? What is the empiric therapy?

Answer 14

Outpatient (WITH comorbidities e.g. chronic heart, lung, liver or renal disease; DM; alcoholism; malignancy; asplenia)

Pathogen:
1. Streptococcus pneumonia
2. Hemophilus influenza
3. Atypicals

Empiric therapy:
1. PO Augmentin / cefuroxime
AND
2. PO Macrolide (clarithromycin / azithromycin) OR doxycycline

(2nd line: PO levofloxacin / moxifloxacin)

Macrolides vs doxycycline:
Look at ADR for atypicals cover

Clarithro vs azithro:
lower CYP3A4, once daily dosing, cheap

Ciprofloxacin does not cover streptococcus p. or atypicals

PO Levofloxacin 750mg OD

Question 15

What is the likely pathogen(s) that cause inpatient non-severe CAP? What is the empiric therapy?

Answer 15

Inpatient Non-Severe
(IV or oral depending on patient’s ability to swallow)

Pathogen:

1. Streptococcus pneumonia
2. Hemophilus influenza
3. Atypicals
4. MRSA
   a. MRSA resp isolate in last 1yr
   b. Hospitalized / Parenteral antibiotics in the last 90days AND positive MRSA PCR screen
5. Pseudomonas aeruginosa
   a. PA resp. isolate in the last 1yr

Empiric therapy:

1. Augmentin / cefuroxime / ceftriaxone
   AND
2. Macrolide (clarithromycin / azithromycin) OR doxycycline

(2nd line: levo / moxifloxacin)
AND

3. IV Vancomycin or PO/IV Linezolid

MODIFY (not add on)

4. Pip-tazo, cefepime, ceftazidime, meropenem, levofloxacin

5 days
7 days (if have MRSA/PA coverage)

Question 16

What is the likely pathogen(s) that cause inpatient severe CAP? What is the empiric therapy?

Answer 16

Inpatient Severe (IV)

Pathogen:

1. Streptococcus pneumonia
2. Staphylococcus Aureus
3. Hemophilus influenza
4. Atypicals
5. MRSA
   a. MRSA resp. isolate in last 1yr
   b. Hospitalized / Parenteral antibiotics in the last 90 days
6. Pseudomonas aeruginosa
   a. PA resp. isolate in the last 1yr
   b. Hospitalization / Parenteral antibiotics in the last 90 days
7. Other Gram negative e.g. klebsiella pneumonia, burkholderia pseudomallei

Empiric therapy:

1. IV Augmentin / Pen G
   AND
2. IV Ceftazidime
   AND
3. IV Macrolide (clarithromycin / azithromycin)

(2nd line: IV levofloxacin / moxifloxacin + ceftazidime)
AND
4. IV Vancomycin or PO/IV Linezolid

Ceftazidime covers burkholderia pseudomallei & pseudomonas aeruginosa

No Doxycycline since no IV form

Pen G + ceftazidime is narrow spectrum

Ceftazidime / levofloxacin would have covered pseudomonas, so no need to modify therapy

5 days or 7 days (if need MRSA/PA coverage)

moxifloxacin can cover bacteroides if anaerobic coverage needed

Question 17

What other things to take note of when treating CAP?

Answer 17

1. If have lung abscess / empyema, reported in radiology investigations, give anaerobe coverage
   a. If standard regimen no anaerobe coverage –> give IV/PO metronidazole / IV/PO clindamycin
   b. Augmentin + ceftazidime + azithromycin
   c. Moxifloxacin + ceftazidime
2. If suspected to have influenza, check and manage influenza in all patients during peak seasons
   a. Add oseltamivir 75mg BD 5days (within 48 hrs, up to 5 days of symptoms onset)
   b. If positive culture/influenza PCR, complete oseltamivir course of 5 days
   c. If no bacterial pathogen evidence (negative culture, low procalcitonin levels, and early clinical stability), stop antibiotics at 48 to 72 hours
3. Avoid using respiratory FQ e.g. Levofloxacin / moxifloxacin as 1st line for CAP
   a. Lots of ADR
   i. Tendinitis, tendon rupture
   ii. QTc prolongation
   iii. Neuropathy
   iv. CNS disturbances
   v. Hypoglycemia
   vi. Arthropathy
   b. Avoid developing resistance against them and other antibiotics
   c. Save for serious gram-negative infection
   i. When have severe penicillin allergy
   ii. Only PO options for pseudomonas aeruginosa
   d. Delay diagnosis of tuberculosis
   e. Undesirable monotherapy if have tuberculosis
4. Adjunctive corticosteroids therapy
   a. Reduce inflammation in lungs
   b. USE if shock refractory (not responding) to fluid resuscitation or vasopressor support
   c. NOT use / conflicting evidence in non-severe or severe CAP respectively
   d. E.g. PO prednisolone, IV dexamethasone, hydrocortisone

Question 18

When to deescalate for CAP?

Answer 18

De-escalation:

When:

• Hemodynamically stable (BP normal)
• Clinically improving
• IV to oral – if patient can take oral meds

How:

• Positive Culture:
  o Follow AST to change to narrow spectrum or
  PO antibiotics
• No culture:
  o Stop coverage for MRSA, pseudomonas, burkholderia within 48 hours (if pathogen not isolated and patient improving)
  o IV to oral –> use either same antibiotics or another antibiotic from the same class (e.g. PO Augmentin + PO clarithromycin)

Question 19

What is the duration of treatment for CAP?

Answer 19

Duration:
- Minimum 5 days
- 7 days if treating MRSA / pseudomonas
- Longer (2-3wks / 3-6 weeks / 6months)
o Deep-seated infections (e.g. lung abscess, meningitis)
o less common pathogen (e.g. TB, burkholderia pseudomallei, fungi)

Question 20

How to monitor response?

Answer 20

Step 4: Monitor Response
Therapeutic:

• should improve within 48 to 72 hrs
• elderly / those with comorbidities might take longer time to improve
• Escalation: Do not escalate within the 1st 72 hours –> let antibiotics work
  o Unless culture-directed or significant clinical deterioration
• Clinical Stability / Improvement:
  o resolution of vital sign abnormalities e.g. heart rate (~70bpm), respiratory rate (12-22 bpm), blood pressure (~120/80 mmHg), oxygen saturation (95-100), temperature (>36 degrees)
  o ability to ingest oral medications
  o baseline mental status
• NO need for radiographic repeats e.g. X-ray
  o Unless significant clinical deterioration
• NO need for lab test e.g. sputum culture, urine culture

Toxicity:

• ADR of antibiotics

Question 21

What are the risk factors for HAP/VAP and the prevention methods?

Answer 21

Patient related factors:

1. Elderly
2. Smoking
3. COPD, cancer, immunosuppression
4. Prolonged hospitalization
5. Coma, impaired consciousness (affect swallowing and breathing)
6. Malnutrition (reduce immunity)

Infection control-related factors:

7. Lack of hand hygiene
8. Contaminated respiratory care device e.g. supplement oxygen mask

Healthcare-related factors:

9. Prior antibiotics use
10. Sedatives
11. Opioid analgesics
12. Mechanical ventilation
13. Supine position

Prevention:

• Practice consistent hand hygiene (infection control)
• Judicious use of antibiotics and medications with sedative effects (health-related)
• VAP specific (healthcare-related)
  o Limit duration of mechanical ventilation
  o Minimize duration and deep levels of sedation
  o Elevate head of bed by 30 degrees

Question 22

What are the subjective evidences for HAP/VAP?

Answer 22

same as CAP

Clinical Presentations of Pneumonia:
Systemic: Fever, chills, malaise, mental status change, tachycardia, hypotension

Local: Cough (dry), chest pain(from coughing), shortness of breath, tachypnea (>24bpm), hypoxia, increased sputum production

Lung auscultation
- Diminished breath sounds when inhaling
- Crackling when lung expands

Question 23

What are the objective evidences for HAP/VAP?

Answer 23

1. Need X-ray
   a. New infiltrates or consolidation (white patches)
2. General Lab test (WBC, CRP, Procalcitonin)
3. Urinary Antigen test (for severe CAP or hospitalized pts)
   a. test whether patient had exposure to it but doesn’t tell whether it was in the past or now since it can still be positive even after on antibiotics
4. Gram stain & Culture
   a. Sputum
   i. Less yield
   ii. Contaminated – by oropharyngeal secretions
   b. Respiratory culture
   i. Bronchoalveolar lavage (BAL)
   ii. Invasive
   iii. Less contaminated
   c. Blood culture (hospital pts)
   i. Rule out bacteremia

Blood and respiratory gram stain and culture done in hospitals for:
Risk factors for DRO e.g. MRSA/PA

1. Empirically treated for MRSA/PA
2. Infected with MRSA/PA in the last 1 year
3. Hospitalized / Parenteral antibiotic in the last 90 days

Question 24

What to consider when treating/deciding on the therapy for HAP/VAP?

Answer 24

Minimally need coverage for Pseudomonas aeruginosa and staphylococcus aureus

Need additional coverage based on:

• MDRO risk factors
• Mortality risk factors
• Hospital’s / unit’s distribution of pathogen-associated with HAP/VAP and their susceptibilities e.g. antibiogram

Cover for MRSA, if:

1. Prior IV antibiotics in the last 90 days
2. Isolation of MRSA in last 1 year
3. Hospitalization in unit where 20% of S. aureus are MRSA
4. High mortality risk e.g. need ventilatory support due to HAP and septic shock

Pseudomonas & GNR – Double antipseudomonal antibiotics from different classes for VAP/HAP empiric treatment:

1. Antimicrobial resistance risk factor
   a. IV antibiotics use in last 90 days
   b. Acute renal replacement therapy (dialysis) prior to VAP onset
   c. Isolation of Pseudomonas aeruginosa in last 1 year
2. Hospitalization in unit with 10% of PA being resistant to monotherapy agent
3. High mortality risk e.g. on mechanical ventilator due to HAP and septic shock
4. VAP??

AVOID use of aminoglycosides as the sole anti-pseudomonal agent

• Nephrotoxicity
• Patients already hypotensive, low blood flow to the kidneys might increase their risk of AKI –> if given aminoglycoside might worsen this
• Don’t penetrate the lung well + don’t go into lung abscess well

Question 25

What are the pathogens that needs to be covered in HAP/VAP?

Answer 25

S. aureus and Pseudomonas Aeruginosa

Question 26

What are all the pathogens in HAP/VAP? What are the empiric therapies for HAP/VAP? What is the duration of treatment?

Answer 26

Pathogens:

1. Pseudomonas aeruginosa
2. Enteric Gram Negative e.g. E. coli, klebsiella influenza, Enterobacter spp.
3. Staphylococcus aureus (look out for risk for MRSA)
   a. Look at criteria (above)
4. Stenotrophomonas / Acinetobacter spp. (anti-pseudomonal agent)

Empiric therapy:

1. Pip-tazo / cefepime / ceftazidime* / meropenem / imipenem
   AND/OR
   (anti-pseudomonal agent)
2. Levofloxacin / ciprofloxacin*
   OR
3. Aminoglycosides (amikacin / gentamicin)
   AND

IV vancomycin / PO/IV linezolid

Duration:

• 7 days (regardless of pathogen)
• Longer (2-3wks)
  o Deep-seated infection e.g. lung abscess / meningitis

Thought process:
Always cover PA, MSSA, GNR
Check if need to cover MRSA
Check if need single or double anti-pseudomonal agents from different classes

Avoid use of ceftazidime or ciprofloxacin if MRSA is omitted, since vancomycin is not used, and these 2 agents only covers gram negs thus gram positives not covered

Question 27

When and how to deescalate for HAP/VAP?

Answer 27

De-escalation:
When:

• Hemodynamically stable (BP normal)
• Clinically improving
• IV to oral – if patient can take oral meds

How:

• Positive Culture:
  o Follow AST to change to narrow spectrum or PO antibiotics
  o Use single anti-pseudomonal agent
• No culture:
  o Maintain coverage base on local HAP/VAP antibiogram
  o If not, continue covering for pseudomonas aeruginosa, enteric GNR (E. coli, Enterobacter, klebsiella) and MSSA
  o IV to oral

Question 28

How to monitor response for HAP/VAP?

Answer 28

Step 4: Monitor Response

Therapeutic:

• should improve within 48 to 72 hrs
• elderly / those with comorbidities might take longer time to improve
• Escalation: do not escalate within the 1st 72 hrs
  o Unless culture directed or significant clinical deterioration
• Clinical stability / improvement:
  o resolution of vital sign abnormalities e.g. heart rate (~70bpm), respiratory rate (12-22 bpm), blood pressure (~120/80 mmHg), oxygen saturation (95-100), temperature
  o ability to ingest oral medications
  o baseline mental status
• NO need for radiographic repeats e.g. X-ray
• NO need for lab test e.g. sputum culture, urine culture

Toxicity:
ADR of antibiotics