Hospital-Acquired Pneumonia Empiric Antibiotic Recommendations
Direct Recommendation
For hospital-acquired pneumonia, initiate piperacillin-tazobactam 4.5g IV every 6 hours as the backbone antibiotic, adding levofloxacin 750mg IV daily for high-risk patients (those requiring ventilatory support, with septic shock, or who received IV antibiotics in the prior 90 days), and adding vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20mg/mL) or linezolid 600mg IV every 12 hours when MRSA risk factors are present. 1, 2
Risk Stratification Algorithm
Step 1: Assess Mortality Risk Factors
High mortality risk is defined by: 1, 2
- Need for ventilatory support due to pneumonia
- Septic shock requiring vasopressors
Step 2: Assess MRSA Risk Factors
MRSA coverage is indicated if any of the following are present: 1, 2
- IV antibiotic use within the prior 90 days
- Treatment in a unit where MRSA prevalence among S. aureus isolates is >20% or unknown
- Prior detection of MRSA by culture or screening
Step 3: Assess Recent Antibiotic Exposure
Dual antipseudomonal coverage is required if: 1
- Patient received IV antibiotics in the prior 90 days (regardless of mortality risk)
Empiric Regimen Selection
Low-Risk Patients (No High Mortality Risk, No Recent IV Antibiotics, No MRSA Risk)
Monotherapy with piperacillin-tazobactam 4.5g IV every 6 hours is sufficient. 1, 2
Alternative monotherapy options include: 2
- Cefepime 2g IV every 8 hours
- Levofloxacin 750mg IV daily
- Imipenem 500mg IV every 6 hours
- Meropenem 1g IV every 8 hours
High-Risk Patients or Recent IV Antibiotic Use
Dual antipseudomonal therapy is required using agents from different classes: 1, 2
Primary regimen: 1
- Piperacillin-tazobactam 4.5g IV every 6 hours PLUS
- Levofloxacin 750mg IV daily (preferred fluoroquinolone for respiratory infections)
Alternative second agents include: 1, 2
- Ciprofloxacin 400mg IV every 8 hours (less preferred than levofloxacin)
- Amikacin 15-20mg/kg IV daily
- Gentamicin 5-7mg/kg IV daily
- Tobramycin 5-7mg/kg IV daily
Critical rule: Never combine two β-lactams together. 1, 2
Adding MRSA Coverage
When MRSA risk factors are present, add one of the following: 1, 2
- Vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20mg/mL)
- Linezolid 600mg IV every 12 hours
Special Populations and Adjustments
Severe Penicillin Allergy
For patients with severe penicillin allergy: 2
- Use aztreonam 2g IV every 8 hours as the antipseudomonal β-lactam
- Critical pitfall: Aztreonam lacks gram-positive activity, so MSSA coverage must be added with vancomycin or linezolid 3, 2
Alternative non-β-lactam regimen for severe allergy: 2
- Levofloxacin 750mg IV daily PLUS aminoglycoside (amikacin, gentamicin, or tobramycin)
- Add vancomycin or linezolid for MRSA coverage if risk factors present
Renal Impairment
Dosing adjustments are necessary for renally cleared antibiotics: 2
- Cefepime, levofloxacin, ciprofloxacin, aminoglycosides, and vancomycin all require renal dose adjustment
- Piperacillin-tazobactam requires adjustment for CrCl <40 mL/min
- Linezolid does not require renal adjustment and may be preferred over vancomycin in severe renal impairment
Treatment Duration
Standard duration is 5-7 days if the patient achieves clinical stability: 3
- Afebrile for 48 hours (temperature ≤37.8°C)
- Heart rate ≤100 beats/min
- Respiratory rate ≤24 breaths/min
- Systolic blood pressure ≥90 mmHg
Critical Pitfalls to Avoid
Do not use azithromycin for HAP, as it lacks antipseudomonal coverage and is not recommended in HAP guidelines. 1
Do not use monotherapy in high-risk patients or those with recent IV antibiotic exposure within 90 days—these patients require dual antipseudomonal coverage. 1, 2
Do not combine two β-lactams (e.g., piperacillin-tazobactam with cefepime), as this provides no additional benefit and increases toxicity risk. 1, 2
When aztreonam is used for severe penicillin allergy, always add gram-positive coverage (vancomycin or linezolid) since aztreonam has no activity against MSSA. 3, 2
Obtain appropriate cultures before initiating antibiotics and consider local antimicrobial resistance patterns, as institutional antibiograms may differ significantly from guideline recommendations. 3, 4
De-escalation Strategy
Once culture results are available: 2
- For confirmed methicillin-sensitive S. aureus (MSSA), narrow to oxacillin, nafcillin, or cefazolin (preferred over broader agents)
- Discontinue MRSA coverage if cultures are negative for MRSA after 48-72 hours
- Discontinue second antipseudomonal agent if susceptibilities allow single-agent therapy