Nosocomial Pneumonia

Question 1

Identifying nosocomial pneumonia

Answer 1

Hospital-acquired pneumonia: Onset ≥ 48h after hospital admission

OR

Ventilator-associated pneumonia: Onset ≥ 48h after mechanical ventilation

Question 2

Epidemiology

Answer 2

2nd most common cause of healthcare-acquired infections

Associated with significant healthcare costs

• Prolonged hospitalization
• Accounts for ≥ 50% of inpatient antibiotic use

Mortality: 20-30%

• HAP: 18.8%
• VAP: 29.3%

Question 3

Risk factors

Answer 3

Patient-related factors:

1) Elderly
2) Smoking
3) COPD, cancer, immunosuppression
4) Prolonged hospitalization
5) Coma, unconsciousness
6) Malnutrition

Infection control-related factors

1) Poor hand hygiene
2) Contaminated respiratory care devices

Healthcare-related factors

1) Prior antibiotic use
2) Opioids, sedatives
3) Mechanical ventilation
4) Supine position

Question 4

Prevention

Answer 4

1) Good hand hygiene
2) Judicious use of antibiotics, sedatives

VAP specific:

1) Limit duration of mechanical ventilation
2) Limit duration & deep levels of sedation
3) Elevate head of bed by 30o

Question 5

Microbiology

Answer 5

Gram-positive:

1) Streptococcus pneumoniae
2) Staphylococcus aureus

Gram-positive:

1) Haemophilus influenzae
2) E. coli
3) Klebsiella pneumonia (including MDR strains)
4) Proteus spp.
5) Enterobacter spp.
6) Serratia marcescens
7) Acinetobacter spp. (including MDR strains)
8) Pseudomonas aeruginosa (including MDR strains)

Question 6

MDRO risk factors

Answer 6

HAP:
1) Prior IV antibiotics in past 90 days

VAP:

1) Prior IV antibiotics in past 90 days
2) Septic shock at time of VAP onset
3) ARDS (acute respiratory distress syndrome) prior to VAP onset
4) ≥ 5 days hospitalization prior to VAP onset
5) Acute renal replacement therapy prior to VAP onset

Question 7

Mortality risk factors

Answer 7

Applies to HAP only

1) Requires mechanical ventilation due to HAP
2) Septic shock

Question 8

How to determine MRSA prevalence

Answer 8

Based on antibiogram
MRSA prevalence
= 100% - [Susceptibility rate of S. aureus to anti-Staphylococcal ß-lactams e.g. Cloxacillin, Cefazolin]

Question 9

Empiric therapy of nosocomial pneumonia

Answer 9

Backbone regimen

• Used with: No MDRO risk factor + No mortality risk factor + No indication for MRSA coverage
• Indicated for ALL nosocomial pneumonia patients

+/- MRSA coverage
+/- Additional Gram-negative coverage

Question 10

Backbone regimen - Organisms to cover

Answer 10

Minimally cover: MSSA + P. aeruginosa

1) S. aureus (MSSA)
2) P. aeruginosa
3) S. pneumoniae
4) Antibiotic-sensitive Enterobacteriaceae
- E. coli
- Klebsiella pneumoniae
- Proteus spp.
- Enterobacter spp.
- Serratia marcescens

Question 11

Backbone regimen - Choice of antibiotics

Answer 11

1st Line: Any one anti-Pseudomonal ß-lactam

1) Piperacillin-Tazobactam
2) Cefepime
- Avoid Ceftazidime –> Poor GP coverage
3) Carbapenems - Meropenem / Imipenem
- Reserved for ESBL-producing strains

Alternative

1) Levofloxacin
- Alternative in penicillin allergy
- Avoid Moxifloxacin –> no P. aeruginosa coverage

Question 12

Backbone regimen - Dosing

Answer 12

Route: IV

Piperacillin-Tazobactam

• IV 4.5g q6-8h
• Renal dose adjustment needed

Cefepime

• IV 2g q8h
• Renal dose adjustment needed

Meropenem

• IV 1g q8h
• Renal dose adjustment needed

Imipenem

• IV 500 mg q6h
• Renal dose adjustment needed

Levofloxacin

• IV 750 mg q24h
• Renal dose adjustment needed

Question 13

Additional MRSA coverage - Indication

Answer 13

HAP

1) ≥ 1 MDRO risk factor OR
2) ≥ 1 Mortality risk factor OR
3) MRSA prevalence > 20% / unknown

VAP

1) ≥ 1 MDRO risk factor OR
2) MRSA prevalence > 10-20% / unknown

Question 14

Additional MRSA coverage - Choice of antibiotics

Answer 14

Add on:

1) Vancomycin OR
- More commonly used
- More experience with using Vancomycin (in terms of dosing, monitoring)
- More cost effective
2) Linezolid

Question 15

Additional MRSA coverage - Vancomycin VS Linezolid

Answer 15

Concerns over Vancomycin

• Variable PK (requires TDM)
• Limited penetration –> decreased ability to reach target concentrations

Advantages of Linezolid

• Predictable PK, good lung penetration
• May improve clinical response in MRSA pneumonia

Overall: No difference in clinical outcomes

Choice depends on:

1) Cost (including TDM costs)
- Vancomycin generally cheaper
2) Blood counts
- Linezolid may cause bone marrow suppression
3) Renal function
- Vancomycin is nephrotoxic
- But generally can control/monitor with TDM –> not a C/I
4) Drug interactions
- E.g. Linezolid + SSRI –> can cause serotonin syndrome

Question 16

Additional MRSA coverage - Dosing

Answer 16

Route: IV

Vancomycin

• IV 15 mg/kg q8-12h
• Renal dose adjustment needed

Linezolid
- IV 600 mg q12h

Question 17

Additional Gram-negative coverage - Indication

Answer 17

HAP:

1) ≥ 1 MDRO risk factor OR
2) ≥ 1 Mortality risk factor

VAP:

1) ≥1 MDRO risk factor OR
2) Single anti-pseudomonal agent with activity < 90% / unknown

Question 18

Additional Gram-negative coverage - Choice of antibiotics

Answer 18

Add on:

1) Gentamicin OR
2) Amikacin OR
3) Tobramycin OR
4) Ciprofloxacin OR
5) Levofloxacin

Antibiotic added on should be of a different class from antibiotic used in backbone regimen
Backbone regimen: ß-lactam - Add on Aminoglycoside / Fluoroquinolone
Backbone regimen: Fluoroquinolone - Add on Aminoglycoside

Question 19

Additional Gram-negative coverage - Dosing

Answer 19

Gentamicin

• IV 5 - 7 mg/kg q24h
• Renal dose adjustment needed

Amikacin

• IV 15 mg/kg q24h
• Renal dose adjustment needed

Tobramycin

• IV 5 - 7 mg/kg q24h
• Renal dose adjustment needed

Ciprofloxacin

• IV 400 mg q8-12h
• Renal dose adjustment needed

Levofloxacin

• IV 750 mg q24h
• Renal dose adjustment needed

Question 20

Additional Gram-negative coverage - Rationale

Answer 20

Proposed benefits

• Extended spectrum of activity
• Synergistic activity
• Prevent resistance
• Note: Most proposed benefits demonstrated in vitro

Potential risks

• Increased cost
• Increased risk of adverse effects

Clinical data
- Additional coverage does not provide improvement in mortality, length of stay, treatment failure rates

Main reason for additional coverage:
- Broaden spectrum of empiric GN coverage in patients with at risk for MDRO or death –> prevent death

Question 21

Duration of treatment

Answer 21

7 days

Question 22

Monitoring

Answer 22

Safety

1) Renal function
- Nephrotoxic: Vancomycin, Aminoglycosides
2) Adverse effects
- E.g. Diarrhoea, rash
- E.g. Bone marrow suppression with Linezolid

Efficacy

1) Clinical improvement expected in 72h (elderly / multiple comorbidities might take longer)
- Resolution/Improvement of symptoms: Decreased cough, chest pain, fever, SOB, WBC, tachypnea, O2 requirement etc.

Therapeutic drug monitoring needed for:

1) Vancomycin
- Monitor: Plasma concentrations, renal function (nephrotoxic), red man syndrome
2) Linezolid
- Monitor: Blood counts (bone marrow suppression)
3) Aminoglycosides
- Monitor: Plasma concentrations, renal function (nephrotoxic)

Question 23

Treatment modification - When to modify

Answer 23

1) Positive cultures & susceptibility results

2) Negative cultures & clinical improvement

Question 24

Treatment modification - How to modify

Answer 24

Positive cultures
- Culture-directed therapy –> based on AST

Negative cultures

• Maintain coverage of GN bacilli (including P. aeruginosa) & MSSA
• Overall: Can de-escalate to backbone regimen, if MRSA/MDRO not found in culture