Nosocomial Pneumonia Flashcards
Identifying nosocomial pneumonia
Hospital-acquired pneumonia: Onset ≥ 48h after hospital admission
OR
Ventilator-associated pneumonia: Onset ≥ 48h after mechanical ventilation
Epidemiology
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%
Risk factors
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
Prevention
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
Microbiology
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)
MDRO risk factors
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
Mortality risk factors
Applies to HAP only
1) Requires mechanical ventilation due to HAP
2) Septic shock
How to determine MRSA prevalence
Based on antibiogram
MRSA prevalence
= 100% - [Susceptibility rate of S. aureus to anti-Staphylococcal ß-lactams e.g. Cloxacillin, Cefazolin]
Empiric therapy of nosocomial pneumonia
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
Backbone regimen - Organisms to cover
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
Backbone regimen - Choice of antibiotics
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
Backbone regimen - Dosing
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
Additional MRSA coverage - Indication
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
Additional MRSA coverage - Choice of antibiotics
Add on:
1) Vancomycin OR
- More commonly used
- More experience with using Vancomycin (in terms of dosing, monitoring)
- More cost effective
2) Linezolid
Additional MRSA coverage - Vancomycin VS Linezolid
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
Additional MRSA coverage - Dosing
Route: IV
Vancomycin
- IV 15 mg/kg q8-12h
- Renal dose adjustment needed
Linezolid
- IV 600 mg q12h
Additional Gram-negative coverage - Indication
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
Additional Gram-negative coverage - Choice of antibiotics
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
Additional Gram-negative coverage - Dosing
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
Additional Gram-negative coverage - Rationale
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
Duration of treatment
7 days
Monitoring
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)
Treatment modification - When to modify
1) Positive cultures & susceptibility results
2) Negative cultures & clinical improvement
Treatment modification - How to modify
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
