CAP

Question 1

Identifying CAP

Answer 1

Onset in community OR < 48h after hospitalization

Question 2

Morbidity & Mortality

Answer 2

~10% require admission to ICU

~10% mortality (especially if antibiotics not started promptly

Question 3

Risk factors

Answer 3

1) ≥ 65 years
2) Smoking
3) Previous hospitalization for CAP
4) Comorbidities e.g. COPD, DM, HF, immunosuppression

Question 4

Microbiology

Answer 4

Outpatient:

1) Streptococcus pneumoniae
2) Haemophilus influenzae
3) Atypicals
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae

Inpatient, non-severe:

1) 1) Streptococcus pneumoniae
2) Haemophilus influenzae
3) Atypicals
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
- Legionella pneumophilia

Inpatient, severe:
1) 1) Streptococcus pneumoniae 
2) Haemophilus influenzae
3) Atypicals
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
- Legionella pneumophilia
4) Staphylococcus aureus
5) Other Gram-negatives e.g.
- Klebsiella pneumonia
- Burkholderia pseudomallei 
• High local incidence 
• Causes melioidosis --> pneumonia is a common presentation

Question 5

Risk stratification - Stratification methods

Answer 5

1) Pneumonia severity index (PSI)
2) CURB-65
3) IDSA/ATS Criteria for severe CAP

Question 6

Risk stratification - Pneumonia severity index (PSI)

1) How it works
2) Classification
3) Clinical practice

Answer 6

How it works:
Used to assess location of treatment
Use 20 variables to stratify CAP patients into 5 mortality risk classes

Classification:
Class I-II: Outpatient
Class III: Short hospitalization/observation
Class IV-V: Inpatient

Clinical practice:
Limited use due to complexity

Question 7

Risk stratification - CURB-65

• How it works
• Classification
• Clinical practice

Answer 7

How it works:
Used to assess location of treatment
Uses 5 variables to stratify CAP patients into 3 mortality risk classes (based on score)

Classification:
Score = 0-1: Outpatient
Score = 2: Inpatient
Score ≥ 3: Inpatient, consider ICU

Clinical practice:
Commonly used
- Easy to use
- Readily available parameters

Question 8

Risk stratification - IDSA/ATS criteria for severe CAP

Answer 8

Severe CAP: ≥ 1 Major symptoms OR ≥ 3 Minor symptoms

Major symptoms:

1) Mechanical ventilation
2) Septic shock requiring vasoactive medication

Minor symptoms:

1) RR ≥ 30 bpm
2) PaO2/FiO2 ≤ 250
3) Multilobar infiltrates
4) Hypothermia - Core temperature < 36oC
5) Uremia - Urea > 7 mmol/L
6) Leukopenia - WBC < 4 x 10^9 / L
7) Hypotension requiring aggressive fluid resuscitation
8) Confusion/Disorientation

Question 9

Management of CAP

Answer 9

Pharmacological treatment:

1) Antibiotic treatment
2) Adjunctive corticosteroid treatment
- NOT recommended

Non-pharmacological:
1) Prevention

Question 10

Prevention

Answer 10

1) Vaccination
- Influenza –> can cause pneumonia as a complication
- Pneumococcal –> protects against S. pneumoniae

2) Smoking cessation

Question 11

Adjunctive corticosteroid treatment

1) Treatment regimen
2) Benefits
3) Limitations
4) Clinical use

Answer 11

Treatment regimens:

1) PO Prednisolone 40mg q24h x 7 days OR
2) IV Dexamethasone 50mg q24h x 4 days

Benefits:

1) Decrease inflammation in lungs –> relieves symptoms
2) May shorten length of stay & time to clinical stability (increase rate of clinical resolution)

Limitations
1) Any impact is small & outweighed by increased risk of hypoglycemia / other ADRs

Clinical use:
NOT routinely recommended

Question 12

Antibiotic treatment - Initiation

Answer 12

Initiate with clinical suspicion

• I.e. Based on clinical presentation (S/Sx, radiographic findings)
• Confirmation with cultures not needed

Question 13

Antibiotic treatment - Treatment regimens

Answer 13

Outpatient
- Standard regimen (for ALL outpatient)

Inpatient (severe VS non-severe)

• Standard regimen (for ALL inpatient)
• Consider need for additional coverage: Anaerobic / MRSA / Pseudomonal coverage

Question 14

Antibiotic treatment - Considerations when choosing antibiotics

• Macrolides
• Fluoroquinolones

Answer 14

Macrolides
- Avoid Erythromycin - associated with more GI side effects

Respiratory Fluoroquinolones
- NOT 1st line - Only used as alternative in penicillin allergy
- Associated with ADRs: Tendonitis, tendon rupture, neuropathy, QTc prolongation, hypoglycemia, CNS disturbances
- High risk of collateral damage
- Delay diagnosis of TB
- Reserve use for other GN infections
• Only oral option for P. aeruginosa
• Alternative against P. aeruginosa, in patients with severe penicillin allergies

Question 15

Standard regimen for OUTpatient - Patient population

Answer 15

Organisms to cover & treatment regimen differs depending on patient population:

1) Generally healthy
2) Certain comorbidities
- Chronic heart, lung, liver, renal diseases
- DM
- Alcoholism
- Malignancy
- Asplenia

Question 16

Standard regimen for OUTpatient - Organisms to cover

Answer 16

Generally healthy:

1) Streptococcus pneumoniae
2) Haemophilus influenzae
3) Atypicals (optional)

Certain comorbidities:

1) Streptococcus pneumoniae
2) Haemophilus influenzae
- Including ß-lactamase producing strains
3) Atypicals

Question 17

Standard regimen for OUTpatient - Choice of antibiotics (generally healthy)

Answer 17

1st Line:

1) Amoxicillin
- Covers S. pneumoniae + H. influenzae

Alternative:

1) Levofloxacin OR Moxifloxacin
- Alternative in penicillin allergy

Question 18

Standard regimen for OUTpatient - Choice of antibiotics (certain comorbidities)

Answer 18

1st line: 
1) Amoxicillin-Clavulanate OR Cefuroxime
- Covers S. pneumoniae + H. influenzae 
PLUS
2) Macrolides (Clarithromycin / Azithromycin) OR Doxycycline
- Covers atypicals 

Alternative:

1) Levofloxacin OR Moxifloxacin
- Alternative in penicillin allergy

Question 19

Standard regimen for OUTpatient - Dosing

Answer 19

Amoxicillin

• PO 1g TDS
• Renal dose adjustment needed

Augmentin

• PO 625 mg TDS OR PO 2g BD
• Renal dose adjustment needed

Cefuroxime

• PO 500 mg BD
• Renal dose adjustment needed

Azithromycin
- PO 500 mg OD

Clarithromycin
- PO 500 mg BD

Doxycycline
- PO 100 mg BD

Levofloxacin

• PO 750 mg OD
• Renal dose adjustment needed

Moxifloxacin
- PO 400 mg OD

Question 20

Standard regimen for INpatient, NON-severe - Organisms to cover

Answer 20

1) S. pneumoniae
2) H. influenzae
- Including ß-lactamase producing strains
3) Atypicals

Question 21

Standard regimen for INpatient, NON-severe - Choice of antibiotics

Answer 21

1st Line:
1) Amoxicillin-Clavulanate OR Ceftriaxone
- Covers S. pneumoniae + H. influenzae
PLUS
2) Macrolides (Clarithromycin / Azithromycin) OR Doxycycline
- Covers atypicals

Alternative:

1) Levofloxacin OR Moxifloxacin
- Alternative in penicillin allergy

Question 22

Standard regimen for INpatient, NON-severe - Dosing

Answer 22

Route:

• ß-Lactam / Fluoroquinolones: IV (may step down to PO later on)
• Macrolides / Doxycycline: PO if possible

Amoxicillin-Clavulanate

• IV 1.2g q8h
• Renal dose adjustment needed

Ceftriaxone
- IV 1 - 2g q24h

Azithromycin
- PO 500 mg OD OR IV 500 mg q24h

Clarithromycin
- PO 500 mg BD OR IV 500 mg q12h

Doxycycline
- PO 100 mg BD

Levofloxacin

• IV 750 mg q24h
• Renal dose adjustment needed

Moxifloxacin
- IV 400 mg q24h

Question 23

Standard regimen for INpatient, severe - Organisms to cover

Answer 23

1) S. pneumoniae
2) H. influenzae
- Including ß-lactamase producing strains
3) Atypicals
4) S. aureus
5) Other GN bacteria e.g.
- Klebsiella pneumonia
- Burkholderia pseudomallei

Question 24

Standard regimen for INpatient, severe - Choice of antibiotics

Answer 24

1st Line:
1) Penicillin G OR Amoxicillin-Clavulanate
- Augmentin preferred –> additional coverage over MSSA, ß-lactamase producing strains
PLUS
2) Ceftazidime
- Covers Burkholderia pseudomallei
PLUS
3) Macrolides (Clarithromycin / Azithromycin) OR Doxycycline

Alternative:
1) Levofloxacin OR Moxifloxacin
- Alternative in penicillin allergy  
PLUS
2) Ceftazidime
- Covers Burkholderia pseudomallei 
- May be used in mild penicillin allergies
- Avoid in severe allergies --> Burkholderia not covered in such cases

Question 25

Standard regimen for INpatient, severe - Dosing

Answer 25

Route: - ß-Lactams / Fluoroquinolones: IV (may step down to PO later) - Macrolides / Doxycycline: PO if possible Amoxicillin-Clavulanate - IV 1.2g q8h - Renal dose adjustment needed Penicillin G - IV 4 million units q6h - Renal dose adjustment needed Ceftazidime - IV 2g q8h - Renal dose adjustment needed Azithromycin - PO 500 mg OD OR IV 500 mg q24h Clarithromycin - PO 500 mg BD OR IV 500 mg q12h Doxycycline - PO 100 mg BD Levofloxacin - IV 750 mg OD - Renal dose adjustment Moxifloxacin - IV 400 mg OD

Question 26

____ may require additional ____ coverage

Answer 26

Inpatient | Anaerobic / MRSA / Pseudomonal

Question 27

Anaerobic coverage - Indications

Answer 27

1) Lung abscess OR | 2) Empyema

Question 28

Anaerobic coverage - Organisms to cover

Answer 28

1) Bacteroides fragilis 2) Porphyromonas spp. 3) Fusobacterium spp. 4) Prevotella spp.

Question 29

Anaerobic coverage - Treatment regimen

Answer 29

Add on: 1) Clindamycin OR 2) Metronidazole Route: PO if possible (else IV) Additional antibiotics only needed if standard regimen has no anaerobic activity - I.e. Not needed if standard regimen includes Augmentin

Question 30

MRSA coverage - Indication

Answer 30

1) Prior respiratory isolation of MRSA in last 1 year OR 2) Severe CAP only: Hospitalization + Prior IV antibiotic use in last 90 days + Locally validated risk factors - Note: Validation of risk factors usually not done in clinical practice

Question 31

MRSA coverage - Choice of antibiotics

Answer 31

1) Vancomycin OR - Recommended 2) Linezolid

Question 32

MRSA coverage - Dosing

Answer 32

Vancomycin - IV 15 mg/kg q8-12h - Renal dose adjustment needed Linezolid - PO 600 mg BD OR IV 600 mg q12h

Question 33

Pseudomonal coverage - Indication

Answer 33

1) Prior respiratory isolate of P. aeruginosa in past 1 year OR 2) Severe CAP only: Hospitalization + Prior IV antibiotic use in last 90 days + Locally validated risk factors - NOT applicable in SG - All inpatient, severe CAP will receive P. aeruginosa coverage due to Ceftazidime (originally used for Burkholderia)

Question 34

Pseudomonal coverage - Choice of antibiotics

Answer 34

``` MODIFY standard regimen to include: 1) Piperacillin-Tazobactam - Generally 1st line anti-Pseudomonal ß-lactam in local hospitals OR 2) Ceftazidime - Poor GP coverage OR 3) Cefepime OR 4) Meropenem - Generally reserved for ESBL-producing strains OR 5) Levofloxacin - Alternative in penicillin allergy ```

Question 35

Pseudomonal coverage - How to modify standard regimen

Answer 35

Initial regimen: Augmentin / Ceftriaxone + Macrolide / Doxycycline Modified regimen: Anti-Pseudomonal ß-lactam + Macrolide OR Doxycycline Initial regimen: Levofloxacin OR Moxifloxacin Modified regimen: Continue Levofloxacin / Switch to Levofloxacin

Question 36

Pseudomonal coverage - Dosing

Answer 36

Piperacillin-Tazobactam - IV 4.5g q6h - Renal dose adjustment needed Ceftazidime - IV 2g q8h - Renal dose adjustment needed Cefepime - IV 2g q8h - Renal dose adjustment needed Levofloxacin - IV 750 mg q24h - Renal dose adjustment needed

Question 37

Duration of treatment

Answer 37

Minimum: 5 days - Must have achieved clinical stability - Most would have achieved clinical stability within 48-72h - Clinical stability: Afebrile, able to maintain oral intake, normal vital signs, oxygen saturation, mental status MRSA / P. aeruginosa: 7 days Burkholderia pseudomallei: 3 - 6 months

Question 38

Monitoring

Answer 38

Safety 1) ADRs e.g. diarrhoea, rash 2) Renal function Efficacy 1) Clinical improvement - Expected in 48 - 72h - Decreased cough, chest pain, SOB, fever, WBC, tachypnea etc. - Elderly/Multiple comorbidities may take longer 2) Radiographic findings - Takes up to 4-6 weeks for resolution - Not used to monitor therapeutic response - Only repeated if clinical deterioration (especially after 72h)

Question 39

Treatment modification - When to modify

Answer 39

1) Culture results come out - Culture directed therapy 2) Clinical deterioration 3) Avoid escalating treatment in first 72h (usually takes 48-72h for improvement) - Exception: Culture-directed / Clinical deterioration 4) Clinical improvement (usually after 48-72h) - De-escalate (e.g. oral step down)

Question 40

Treatment modification - What to modify

Answer 40

Stop empiric coverage of MRSA / P. aeruginosa after 48h if: - No MRSA / P. aeruginosa found in culture AND - Clinical improvement Stop empiric coverage of Burkholderia pseudomallei if: - Not found in culture AND - Clinical improvement Oral step down therapy

Question 41

Oral step down therapy - Indication

Answer 41

ALL of the following are met: 1) Hemodynamically stable (normal BP) 2) Afebrile ≥ 24h 3) Clinical improvement 4) Able to ingest PO medications 5) Normally functioning GIT

Question 42

Oral step down therapy - Benefits

Answer 42

1) Increase patient comfort & mobility 2) Decrease risk of nosocomial-associated bloodstream infections 3) Decrease phlebitis 4) Decrease preparation & administration time 5) Decrease costs 6) Facilitate discharge

Question 43

Oral step down therapy - Step down process

Answer 43

1) Clinically stable for 48 - 72h 2) Step down to PO antibiotics 3) Monitor for another day (optional) 4) Discharge to complete course at home

Question 44

Oral step down therapy - Choice of antibiotics (positive cultures available)

Answer 44

Positive cultures available: Step down based on susceptibility results Note: Levofloxacin is the only PO agent available for P. aeruginosa

Question 45

Oral step down therapy - Choice of antibiotics (no positive cultures available)

Answer 45

``` Choose same antibiotic / same class Should have similar coverage to standard regimen / initial IV antibiotics MRSA / P. aeruginosa / Burkholderia coverage NOT needed ``` Non-severe patients: 1) IV Augmentin OR IV Ceftriaxone - Switch to PO Augmentin OR PO Cefuroxime 2) IV Macrolides - PO available 3) IV Fluoroquinolones - PO available Severe patients 1) IV Augmentin OR IV Penicillin G - Switch to PO Augmentin OR PO Cefuroxime 2) IV Ceftazidime - Discontinue 3) IV Macrolides - PO available 4) IV Fluoroquinolones - PO available